Reproductive System - Lecture Slides PDF

Reproduction, Development and Pregnancy Dr Lihle Qulu F517 [email protected]  Mammalian sex determination is Adult male Adult female regulated by chromosomes. XY...

Reproduction, Development and Pregnancy Dr Lihle Qulu F517 [email protected]  Mammalian sex determination is Adult male Adult female regulated by chromosomes. XY XX (46 chromosomes each) Females have two X chromosomes. Growth (XX) by Meiosis Growth mitosis by mitosis Males have a single X and a small Y (XY) Testes Ovaries Sperm Ovum Testis determining factor (TDF) is (23) (23) located in the Y chromosome Embryonic testes secrete Zygote testosterone (46) responsible for secondary sex organs and external genitalia Absence of testes leads to female accessory sex organ development  Sperms carrying X or Y chromosome 23 chromosomes from ovum and sperm about to fuse Zygote (46) FERTILIZATION Growth by mitosis  Formation of testes and ovaries Male sex is determined by the presence of the Y gene (XY) However in rare cases you get XX male babies One of the X chromosomes contains a segment of the Y chromosomes XY females were found to be missing the same portion of the Y chromosome found in XX males The gene for TDF is found on the short arm of chromosome Y This gene is known as SRY (sex-determining region of the Y) Error in placing SRY in X chromosome seems to occur in meiosis during sperm cell formation  The presence of a Y chromosome means the embryo will become male, even if the zygote also has multiple X chromosomes. For instance, an XXY zygote will become male. A zygote that inherits only a Y chromosome (YO) will die because the larger X chromosome contains essential genes that are missing from the Y chromosome. Once the ovaries develop in a female foetus, one X chromo-some in each cell of her body is inactivated and condenses into a clump of nuclear chromatin known as a Barr body. (Barr bodies in females can be seen in stained cheek epithelium.) The selection of the X chromosome that becomes inactive during development is random: Before differentiation, the embryonic tissues are considered bipotential because they cannot be morphologically identified as male or female. The bipotential gonad has an outer cortex and an inner medulla Under the influence of the appropriate developmental signal, the medulla will develop into a testis. In the absence of that signal, the cortex will differentiate into ovarian tissue.  TDF No TDF Indifferent gonads Wolffian duct Mϋllerian duct Testes Ovaries Testosterone MIF (Müllerian inhibiting factor) No testosterone No MIF Müllerian (Paramesonephric) Müllerian duct duct, patent degenerates Wolffian (Mesonephric) Testes do not develop Uterus and duct patent uterine tubes Other embryonic structure Other embryonic structure Epididymis Ductus deference Prostate, penis, Vagina, labia, clitoris scrotum Seminal vesicles Ejaculatory ducts Wolffian duct – male accessory organs Müllerian duct – female accessory organs  The SRY gene produces a protein (testis-determining factor or TDF) that binds to DNA and activates additional genes, including SOX9, WT1 (Wilms tumor protein), and SF1 (steroidogenic factor). The protein products of these and other genes direct development of the gonadal medulla into a testis. Note that testicular development does not require male sex hormones such as testosterone. The developing embryo cannot secrete testosterone until after the gonads differentiate into testes. Once the testes differentiate, they begin to secrete three hormones that influence development of the male internal and external genitalia. Testicular Sertoli cells secrete glycoprotein anti-Müllerian hormone (AMH; also called Müllerian-inhibiting substance). Testicular interstitial (Leydig) cells secrete androgens {andro-,male}: testosterone and its derivative dihydrotestosterone (DHT). Testosterone and DHT are the dominant steroid hormones in males. Both bind to the same androgen receptor, but the two ligands elicit different responses.  Early growth -- Indifferent gonads Sex determined by TDF Testes Ovaries Seminiferous Interstitial tubules cells Follicles Germinal Form spermatozoa by meiosis Seminiferous tubules Nongerminal Sertoli cells – nurture developing sperm cells Leydig (interstitial ) cells Endocrine tissue of testes- testosterone Mϋllerian inhibiting factor is secreted by the seminiferous tubules - Sertoli cells Leydig cells secrete testosterone resulting in the Wolffian ducts developing into male accessory organs epididymis ductus deferens seminal vesicles ejaculatory duct In the first 6 weeks, the external genitalia are identical 2. Labiosacral folds They share a common – urogenital sinus 4. Genital tubercle - genital tubercle - urethral folds 5. Urethral folds - labioscrotal swellings 8. Urogenital sinus Secretion of testosterone results in masculinisation forming the penis and spongy urethra  In the absence of testosterone 11 week old foetus genital tubercle form the clitoris 4. Penis 6. Scrotum labiosacral swellings – labia majora (scrotum) 13 week old foetus 3. Clitoris 4. Labia majora Urethral folds – urethra and corpora / labia minora Urogenital sinus - bladder  Male reproduction Testosterone does not directly influence the masculinisation of embryonic structures The active ingredient is the steroid hormone Dihydrotestosterone (DHT) Once inside the target organ testostrone is converted to DHT by 5α-reductase Testosterone Testosterone 5α-reductase DHT DHT is needed for the development and maintenance of penis spongy urethra prostate Testosterone directly stimulates the wolffian duct derivates epididymis ductus deferens ejaculatory duct seminal vesicles  Reproductive system development Days Trimester Indifferent Male Female 19 First Germ cells migrate to yolk sac 25-30 Wolffian ducts develop 44-48 Mϋllerian ducts develop 50-52 Urogenital sinus and tubercle 53-60 Tubules and Sertoli cells appear Mϋllerian ducts regress 60-75 Leydig cells appear Formation of vagina Secrete testosterone begins Wolffian ducts grow Wolffian duct regresses 105 Second Ovarian follicles develop 120 Uterus formed 160-260 Third Testes descend into Formation of vagina scrotum completed Growth of external genitilia occurs Male reproduction TESTES (Gonads) Primary male reproductive organs. Oval in shape and are suspended inside a sac (scrotum) by the spermatic cord The spermatic cords 1. Vas (ductus) deferens 2. arteries 3. veins Spermatic cord 4. lymphatics 5. Nerves All are bound together by connective tissue. Testis Scrotum  Male Reproductive System Main structures: 1. Testes 2. Reproductive ducts epididymis, vas deferens, ejaculatory duct, urethra 3. Accessory glands seminal vesicles, prostate gland, bulbourethral glands 4. Supporting structures scrotum, penis, spermatic cords  Testes Egg shaped organ Produce sperm (exocrine function) – seminiferous tubules testosterone (endocrine function) – interstitial cells descend into scrotum just before birth through inguinal canal Each testis is encapsulated by a tough, white, fibrous tissue called the tunica albuginea. The interior of the testis is divided into 250 lobules (small lobes). Each lobule contains 1 to 4 highly coiled, convoluted tubules - seminiferous tubules Interstitial cells are found in the connective tissue surrounding the seminiferous tubules The tubules (seminiferous) unite to form a complex network of channels called the rete testis. The rete testis give rise to several ducts that join the epididymis The scrotum is a sac of skin and superficial fascia that hangs outside the abdominopelvic cavity at the root of the penis and houses the testes Provides an environment three degrees below the core body temperature Responds to temperature changes Adjacent Sertoli cells in a tubule are linked to each other by tight junctions that form an additional barrier between the lumen of the tubule and the interstitial fluid outside the basal lamina. These tight junctions are sometimes called the blood-testis barrier because functionally they behave much like the impermeable capillaries of the blood-brain barrier, restricting movement of molecules between compartments. The seminiferous tubules are involved in sperm cell production - spermatogenesis Spermatogenesis involves 5 stages: Spermatogonia – mitosis primary spermatocyte - meiosis I secondary spermatocyte - meiosis II spermatid - maturation of sperm spermatozoa In embryonic development germ cells migrate to the testes Spermatogenic stem cells = spermatogonia diploid (2n) = 46 chromosomes outer regions of seminiferous tubules Spermatogonia that undergo meiosis are primary spermatocytes Two cells formed = secondary spermatocytes (1n) (haploid) This is the first meiotic division Secondary spermatocytes undergo meiosis II Two haploid spermatids are produced Each primary spermatocyte produces 4 spermatids The spermatids produced are interconnected To produces separate mature spermatozoa requires the participation of the Sertoli cells This process is called spermiogenesis Sertoli cells secrete factors that regulate spermatogenesis and spermiogenesis Spermatids remain embedded in the apical membrane of Sertoli cells while they complete the transformation into Functions of Sertoli Cells Supportive: nutrients, waste materials from spermiogenesis to blood and lymph Phagocytotic: residual bodies shed by spermatids, effete cellular material Secretory: 8th week – Mullerian inhibitory substance: suppress further development of duct. Prepubertal: prevent meiotic division of germinal epithelial cells Sexually mature: Androgen binding protein (FSH dependent) Protective: Blood-testis barrier- Occluding junctions  Each spermatozoon consists of:  Head chromosomes (DNA) acrosome Acrosome has the enzymes necessary for dissolving the ovum membrane and help in fertilization.  Mid Piece: Spermatids remain embedded in the apical membrane of Sertoli cells while they complete the transformation into stores mitochondria for sperm, losing most of their cytoplasm and developing a energy production flagellated tail.  Tail is made of flagella necessary for motility The chromatin of the nucleus condenses into a dense of the sperm. structure that fills most of the head, while a Golgi-derived vesicle called an acrosome flattens out to form a cap over the tip of the nucleus. The acrosome contains enzymes essential for fertilization. Sperm production begins at puberty and continues throughout life, The entire development process from spermatogonium division until sperm release—takes about 64 days. The staggering of developmental stages allows sperm production to remain nearly constant at a rate of 200 million sperm per day. Once sperm form they move into the epididymis for maturation and storage Stored in epididymis for 12 days and later destroyed by macrophages [sperm stored as non-motile within lumen of seminiferous tubules, epididymis, vas deferens  Duct System Epididymis Posterior to the testis First site of sperm maturation consists of a highly coiled tube that provides a place for immature sperm to mature and to be expelled during ejaculation Ductus deferens Extends from the epididymis to the ejaculatory duct Ampulla final enlargement of the duct deferens. Ejaculatory Ducts Start at the junction of the ampulla with the duct of the seminal vesicle Formed by the ductus deferens and seminal vesicles Ductus deferens and seminal vesicles converge just before they enter the prostate gland Ejaculatory ducts open into the prostatic urethra Its function is to convey sperm cells to the urethra.  Accessory glands Seminal vesicles Produce seminal fluid Secretion forms 70-80% of ejaculate fructose, other sugars, prostaglandins, proteins, amino acids, citric and ascorbic acid Secretion is thick yellow alkaline Fructose gives nourishment and energy Prostaglandins help in muscular contractions to help move sperm in female reproductive tract Contractn of SM propels secretion into ejaculatory duct Prostate Secretes prostatic fluid Fluid contains citric acid, calcium and coagulation proteins Secretions account for nearly 30 percent of the volume of semen The slightly acidic secretions help semen clot following ejaculation and then break down the clot. Clot breakdown involves hydrolytic action of fibrinolysin Bulbourethral glands (Cowper’s glands) pea-sized structures located on the sides of the urethra just below the prostate gland During sexual arousal secretes a clear, slippery secretion – pre-ejaculate Fluid empties into the urethra helps lubricate the urethra for the spermatozoa neutralizes any acidity that may be present due to residual drops of urine in the urethra When ejaculating, seminal vesicle contents are emptied into the ejaculatory ducts. This action greatly increases the volume of fluid that is discharged by the vas deferens. Semen Formed by sperm plus fluid from the accessory glands Urethra Important organ in both urinary and reproductive systems. In reproduction, transports sperm through the penis to outside the body.  Erection, Emission and Ejaculation Erection Accompanied by increase in length and width of penis Due to blood flow into erectile tissue of penis Erectile tissue: -Two paired corpora cavernosa - Unpaired corpus spongiosum Erection is due to parasympathetic innervation Vasodilation of arterioles Neurotransmitter involved is nitric oxide Venous outflow is partially occluded – aids erection Corpus spongiosum  Parasympathetic axon Parasympathetic ACh Vascular endothelial axon cells Stimulates L-Arginine eNOS Nitric oxide NO Vascular smooth GTP muscle cell Activates guanylate cyclase cGMP Decreased Smooth muscle cytoplasmic relaxes PDE Ca2+ 5‫ י‬GMP Engorgement of erectile tissue Viagra Ca2+ Channel Ca2+ Erection closed  Erection, Emission and Ejaculation Emission Movement of semen into the urethra Ejaculation Forcible expulsion of semen from the urethra Both processes are controlled by sympathetic innervation Innervation causes peristaltic contractions of tubular system seminal vesicles and prostate muscles at the base of the penis Male sexual function requires synergistic action of Parasympathetic and sympathetic systems  Human sexual response Similar in both sexes divided into four phases Excitation (Arousal) - myotonia (increased muscle tone) - vasocongestion nipple erection in both sexes (more evident in females) clitoris swells (similar to erect penis in males) also labia minora (twice previous size) vagina produces vaginal lubrication considerable enlargement of uterus breast enlargement –women who have never breast-fed a baby Plateau Enlarged labia minora partially hides clitoris (continued engorgement) Swollen areola partially hides the nipples  Human sexual response Orgasm Lasts only a few seconds The uterus and outer third of vagina contract several times Analogous to contractions during ejaculation Resolution Body returns to pre- excitation state Men enter refractory period may produce an erection but cannot ejaculate Women do not have refractory period and therefore can attain multiple orgasms Semen: Is a secretion consisting of  motile sperms secreted from testis,  secretions of seminal vesicles, prostrate and bulbourthral glands In order to fertilize an egg, sperm has to undergo capacitation Acrosomal membrane breaks and releases enzymes for sperm to penetrate egg. The route taken by the sperm is Testis - Epididymis - Vas deferens - Urethra - Penis  CONTROL OF MALE REPRODUCTIVE FUNCTION Erection Two areas of the CNS Hypothalamus Sacral region of spinal cord Conscious thoughts from cerebral cortex act via the hypothalamus to control the sacral region Sacral region increases parasympathetic innervation leading to an erection Sensory stimulation of the penis can activate the parasympathetic innervation (conscious thought not required for an erection to occur ) hypothalamus  neural info (from within body + ext environment) secretes GnRH anterior pituitary  GnRH stimulates release FSH & LH gonads (target tissues of gonadotrophins)  FSH (male) ctrls spermatogenesis LH stimulates steroidogenesis * testosterone essential for spermatogenesis - only in presence FSH and/or LH  Feedback control testosterone (circulating) feedback to: hypothalamus  inhibit GnRH anterior pituitary  some LH inhibition inhibin (prod during spermatogenesis) feedback pituitary  inhibits FSH Sertoli cells possess FSH receptors... if FSH binds to receptors then...   synthesis of ABP (androgen-binding protein) Which ensures presence high conc [androgens / testosterone] in seminif. tubules for spermatogenesis  secretion of inhibin Which inhibits FSH negative feedback  Sex steroid synthesis in Leydig cells. *Androgens: testosterone dehydroepiandrosterone (DHEA) androstenedione * oestrogens Sex steroid synthesis  cholesterol - precursor all gonadal steroids  pregnenolone – key intermediate tissues synthesising steroid sex hormones: testis, ovary, placenta all use same basic biochemical pathway ( amnt final products depends availability enzymes for various rxns)  testosterone ( Leydig cells) diffuses into blood … 1. binds to plasma proteins  GBG ( gonadal steroid- binding globulin)  albumin 2. does not bind & enters target cells  testosterone converts dihydrotestosterone ( more potent)   intracellular functions  degrades to inactive products ( liver) & excreted EFFECTS OF ANDROGENS: secondary sex characteristics hair - pubic region, chest, face, hair recession voice – vocal cords thicken / enlargement larynx/ voice deep skin changes -   activity sebaceous glands / acne. ( fe) males musculature - protein anabolic effect. skeleton - promotion of bone growth. behaviour – aggression, increased libido Testosterone slightly effects basal metabolic rate red blood cell count - stimulates erythropoietin synthesis electrolyte balance - some sodium / water retention Female Reproduction Ovaries * paired abdominal organs * one ovum prod by one ovary (each reproductive cycle) breaks through ovarian wall enters the abdominal cavity  Fallopian tubes (oviducts ~ 10-15 cm long) at ovulation  ovum enters tube (fimbriated end)  travels along tube (facilitated by cilia/smooth muscle) at fertilisation  if sperm present, fertilisation may occur  secretions from tube wall nourish zygote en route to uterus oestrogen & progesterone influence... * movement of cilia * smooth muscle contraction * secretion of mucus from mucosal glands  Uterus (womb) continuous with uterine tube lumen pear shaped muscular organ between the bladder and the rectum Perimetrium: outer connective tissue layer Myometrium: middle smooth muscle layer Endometrium: inner epithelial layer Endothelium stratified, squamous nonkeratinized epithelium stratum basale Stratum functionale: more superficial Grows cyclically as a result of oestrogen and progesterone stimulation Shed during menstruation  Cervix (neck) Uterus narrows to form a cervix Cervix opens into the vagina Vagina Connects reproductive tract with the external environment Physical barrier between vagina and uterus is a plug of cervical mucous Vagina, uterus and uterine tube form the accessory female sex organs These are affected by gonadal steroid hormones During puberty, hypothalamus  secretes gonadotrophin releasing hormone (GnRH) to stimulate anterior pituitary  Anterior pituitary secretes  FSH to stimulate follicle development in the ovary and  LH for ovulation. Breast (mammary gland) lobes (15- 20) divided by adipose tissue – has nothing to do with ability to nurse subdivided into lobules containing glandular alveoli secrete milk in lactating female milk is secreted into a series of secondary tubules tubules converge to form a series of mammary ducts converge to form a lactiferous duct – drains into tip of nipple lumen expands to form an ampulla (milk accumulation  Female reproductive system Ovaries (Gonads) Primary female reproductive organs Exocrine portion – produce the ova Contain a number of follicles Each follicle encloses an ovum Endocrine portion – produce oestrogen and progesterone  Ovarian Cycle The ovary consists of outer cortex and inner medulla Cortex: has developing Ovarian follicles throughout the cortex Medulla: consists of blood and lymphatic vessels along with nerve fibers Oogenesis Formation and growth of an ovum in an ovary Germ cells migrate into the ovaries during embryonic development Towards the end of gestation they divide by meiosis forming primary oocytes (2n) At birth there are about 2 million primary oocytes Contained in a hollow ball of cells ovarian (primordial) follicle About 400 000 at puberty 400 ovulate during reproductive life Ovarian cycle Primary oocytes not stimulated to complete meiosis 1 are contained in primary follicles Immature primary follicles are surrounded by a single layer of follicle cells FSH stimulates the oocyte and the follicle to enlarge = granulosa cells now surround the oocyte Some primary follicles enlarge and form fluid vesicles = secondary follicles The granulosa cells form a ring around the oocyte= corona radiata Has 2 -3 layers of follicular cells that provide a protein supply to the ovum It is attached to a protective layer of the ovum = zona pellucida  Menstrual cycle overview Divided into phases based on changes in the ovaries and endometrium Endometrium Menstrual Ovaries Proliferative Follicular phase: menstruation day I until ovulation Secretive Luteal phase: ovulation until day I of menstruation  Late Luteal Phase and Menstruation: The corpus luteum has an intrinsic life span of approximately 12 days. If pregnancy does not occur, the corpus luteum spontaneously undergoes apoptosis. As the luteal cells degenerate, progesterone and estrogen production decrease. This fall removes the negative feedback signal to the pituitary and hypothalamus, so secretion of FSH and LH increases. The remnants of the corpus luteum become an inactive structure called a corpus albicans {albus, white} Maintenance of a secretory endometrium depends on the presence of progesterone. When the corpus luteum degenerates and hormone production decreases, blood vessels in the surface layer of the endometrium contract. Without oxygen and nutrients, the surface cells die. About two days after the corpus luteum ceases to function, or 14 days after ovulation, the endometrium begins to slough its surface layer, and menstruation begins. Menstrual discharge from the uterus totals about 40 mL of blood and 35 mL of serous fluid and cellular debris. There are usually few clots of blood in the menstrual flow because of the presence of plasmin, which breaks up clots. Menstruation continues for 3–7 days, well into the follicular phase of the next  Menstruation (Ovarian cycle) Follicular phase Average for menstruation 4 – 5 days Ovaries contain only primordial and primary follicles Follicular phase Luteal phase Oestrogen and progesterone levels low Some follicles grow and become secondary follicles One follicle from one ovary becomes graafian follicle Granulosa cells secrete oestrogen Oestrogen levels highest 2 days before ovulation  Menstruation (Ovarian cycle) Follicular phase Follicular growth and oestrogen secretion dependent on FSH secretion Follicular phase Luteal phase Increase in oestrogen augments anterior pituitary response to GnRH stimulation Anterior pituitary responds to GnRH stimulation by secreting LH  Menstruation (Ovarian cycle) Follicular phase LH surge begins 24 hrs before ovulation Peak 6 hrs prior to ovulation Follicular phase Luteal phase Surge responsible for ovulation Since GnRH stimulates both LH and FSH secretion FSH also shows a smaller surge Ovulation FSH stimulates graafian follicle to enlarge Thin walled blister on ovary surface Increase in growth accompanied by increase in oestrogen secretion Rapid oestrogen increase triggers LH secretion on day 13 LH surge triggers follicle rupture on day 14 Ovulation occurs and secondary oocyte is released  Luteal phase Following ovulation empty follicle stimulated by LH It forms the corpus luteum Oestrogen and progesterone Progesterone levels rise rapidly following ovulation – peak in luteal phase Peak is approx 1 week after ovulation  Luteal phase Corpus luteum also secretes inhibin Progesterone and oestrogen increase exert negative feedback on LH and FSH secretion Inhibin suppresses FSH secretion and action This serves to retard new follicle growth Avoidance of multiple ovulations Follicle stimulating hormone Prepares for the release of the ovum by stimulating the follicles that are located in the ovaries Luitenizing hormone: maintain egg development. Levels surge when ovulation occurs, leading to the release of an ovum. If no fertilization (day 22) corpus luteum regresses Inhibin secretion decreases Progesterone and oestrogen levels also fall New follicles begin to grow The withdrawal of ovarian hormones causes menstruation and a new cycle begins  Summary of menstrual cycle A typical menstrual cycle is 28 days long. 1.Three to five days of menstruation shedding of the uterine lining hormone levels are low.  Summary of menstrual cycle 2. At the end of menstruation Anterior Pituitary secretes FSH stimulates new follicles to develop in the ovary follicles secrete oestrogen as they mature cells in the lining of the uterus to proliferate one mature follicle releases an ovum  Summary of menstrual cycle 3. Empty follicle forms the corpus luteum endocrine body that secretes progesterone and oestrogen added influence of progesterone thickens uterine lining further swells in preparation for the implantation of a fertilized egg. no fertilization, corpus luteum dies and hormone levels fall. uterine lining disintegrates and discharges new menstrual period and cycle begins  Ovarian steroidogenesis precursor of all ovarian steroids cholesterol ( from blood / synth.from acetate)   conversion pregnenolone     two pathways Delta 5 pathway ( tertiary follicles) pregnenolone hydroxypregnenolone dehydroepiandrosterone ( weak androgen) Delta 4 pathway ( corpus luteum) pregnenolone progesterone ( blood, to target tissues) hydroxyprogesterone & androstenedione Cholesterol Steroidogenesis 20,22 desmolase Pregnenolone 17α hydroxylase 17-OH- Pregnenolone DHEA Progesterone 17α hydroxylase 17-OH-Progesterone Androstenedione 21β-hydroxylase 21β- hydroxylase 11- Deoxycorticosterone 11- Deoxycortisol 11 hydroxylase 21β-hydroxylase Testosterone Corticosterone 11 hydroxylase Aromatase 18- hydroxylase Aldosterone Cortisol Oestradiol ACTIONS OF OVARIAN STEROIDS ON TARGET TISSUES OESTROGEN function: growth & proliferation Fallopian tubes: effects mucosa proliferation glandular tissue increase ciliated cells / ciliary activity Breasts proliferation of mamm. ducts deposition of fat (puberty) Uterus uterine contractility (pregnancy/ birth) Skeleton increased activity osteoblasts facilitates union epiphyses & diaphyses (limit growth in height) Pelvis broaden "outlet" of pelvis Protein metabolism protein anabolic effect uterus, breasts & skeleton Basal metabolic rate increase BMR slightly Fat deposition fat deposition in breasts, thighs & buttocks Skin increase vascularity & soften texture Water and electrolyte balance some sodium & water retention PROGESTERONE promotes secretory changes Breasts development lobules & alveoli swelling & tenderness (luteal phase) - fluid accumulation Fallopian tubes secretory changes... nutrition of ovum Uterus changes endometrium in preparation for implantation reduces uterine contractility – (pregnancy) Electrolyte balance some sodium & water retention Contraceptives Are Designed to Prevent Pregnancy Contraceptive practices fall into several broad groups. Abstinence, the total avoidance of sexual intercourse, is the surest method to avoid pregnancy (and sexually transmitted diseases). Some couples practice abstinence only during times of suspected fertility calculated using fertility-awareness methods of birth control. Sterilization is the most effective contraceptive method for sexually active people, but it is a surgical procedure and is not easily reversed. Female sterilization is called tubal ligation. It consists of tying off and cutting the Fallopian tubes. A woman with a tubal ligation still ovulates, but the eggs remain in the abdomen. The male form of sterilization is the vasectomy, in which the vas deferens is tied and clipped. Sperm are still made in the seminiferous tubules, but because they cannot leave the reproductive tract, they are reabsorbed.  Interventional methods of contraception include: (1) barrier methods, which prevent union of eggs and sperm; (2) methods that prevent implantation of the fertilized egg; and (3) hormonal treatments that decrease or stop gamete production. The efficacy of interventional contraceptives depends in part on how consistently and correctly they are used. Diaphragm are rubber domes and a smaller version called a cervical cap are usually filled with a spermicidal cream, then inserted into the top of the vagina so they cover the cervix. One advantage to the diaphragm is that it is non-hormonal. When used properly and regularly, diaphragms are highly effective (97–99%). However, they are not always used because they must be inserted close to the time of intercourse, and consequently about 20% of women who depend on diaphragms for contraception are pregnant within the first year. Another female barrier contraceptive is the contraceptive sponge, which contains a spermicidal chemical. The male barrier contraceptive is the condom, a closed sheath that fits closely over the penis to catch ejaculated semen. Males have used condoms made from animal bladders and intestines for centuries.  Condoms are latex may cause allergic reactions, and there is evidence that HIV can pass through pores in some condoms currently produced. A female version of the condom is also commercially avail-able. It covers the cervix and completely lines the vagina, providing more protection from sexually transmitted diseases. Implantation Prevention Some contraceptive methods do not prevent fertilization but do keep a fertilized egg from establishing itself in the endometrium. They include intrauterine devices (IUDs) as well as chemicals that change the properties of the endometrium. IUDs are copper-wrapped plastic devices that are inserted into the uterine cavity, where they kill sperm and create a mild inflammatory reaction that prevents implantation. They have low failure rates (0.5% per year) but side effects that range from pain and bleeding to infertility caused by pelvic inflammatory disease and blockage of the Fallopian tubes. Some IUDs contain progesterone-like hormones. Hormonal Treatments Techniques for decreasing gamete production depend on altering the hormonal milieu of the body. Types of hormonal contraceptives include: oral contraceptive pills, injections lasting months, or a vaginal contraceptive ring.  The oral contraceptives, also known as birth control pills, rely on various combinations of oestrogen and progesterone that inhibit gonadotropin secretion from the pituitary. Without adequate FSH and LH, ovulation is suppressed. In addition, progesterone's in the contraceptive pills thicken the cervical mucus and help prevent sperm penetration. These hormonal methods of contraception are highly effective when used correctly but also carry some risks, including an increased incidence of blood clots and strokes, especially in women who smoke. Development of a male hormonal contraceptive has been slow because of undesirable side effects. Contraceptives that block testosterone secretion or action are also likely to decrease the male libido or even cause impotence. Both side effects are unacceptable to men who would be most interested in using the contraceptive. Some early male oral contraceptives irreversibly suppressed sperm production, which was also unacceptable. A number of clinical trials are currently looking at both hormonal and non-hormonal methods for decreasing male fertility Fertilisation process Sperm deposited in the female reproductive tract must go through their final maturation step, capacitation, which enables the sperm to swim rapidly and fertilize an egg. The process involves changes in lipids and proteins of the sperm head membrane. An egg can be fertilized for only about 12–24 hours after ovulation. Sperm in the female reproductive tract remain viable for 5–6 days. They bind to the epithelium of the Fallopian tube while awaiting a chemical signal from a newly ovulated egg.  Fertilization normally takes place in the distal part of the Fallopian tube. Of the millions of sperm in a single ejaculation, only about 100 reach this point. To fertilize the egg, a sperm must penetrate both an outer layer of loosely connected granulosa cells (the corona radiata) and a protective glycoprotein coat called the zona pellucida. To get past these barriers, capacitated sperm release powerful enzymes from the acrosome in the sperm head, a process known as the acrosomal reaction. The enzymes dissolve cell junctions and the zona pellucida, allowing the sperm to wiggle their way toward the egg. The first sperm to reach the egg quickly finds sperm-binding receptors on the oocyte membrane and binds to the egg. The fusion of sperm and oocyte membranes triggers a chemical reaction called the cortical reaction that excludes other sperm. In the cortical reaction, membrane-bound cortical granules in the peripheral cytoplasm of the egg release their contents into the space just outside the egg membrane. These chemicals rapidly alter the membrane and surrounding zona pellucida to prevent polyspermy, in which more than one sperm  To complete fertilization, the fused section of sperm and egg membrane opens, and the sperm nucleus sinks into the egg’s cytoplasm. This signals the egg to resume meiosis and complete its second division. The final meiotic division creates a second polar body, which is ejected. At this point, the 23 chromosomes of the sperm join the 23 chromosomes of the egg, creating a zygote nucleus with a full set of genetic material. Once an egg is fertilized and becomes a zygote, it begins mitosis as it slowly makes its way along the Fallopian tube to the uterus, where it will settle for the remainder of the gestation period. Zygote to morula Following fertilization - Secondary oocyte completes meiosis II pre-embryo divides mitotically (2, 4, 8 cells etc) passage through oviduct. known as morula (ball of ≥ 8 cells) enters uterus as blastocyst (after 3-4 days) Blastocyst (fluid-filled ball of cells) chorion (trophoblast cells) single outer layer - develops to placenta inner cell mass below trophoblast - develops into embryo Blastocyst remains free in uterine cavity for 2-3 days Obtains nutrients from uterine endometrial secretions called “uterine milk” Day 6: blastocyst attaches to uterine wall Implantation results from the action of trophoblast cells that develop over the surface of the blastocyst.  The dividing embryo takes four or five days to move through the Fallopian tube into the uterine cavity. Under the influence of progesterone, smooth muscle of the tube relaxes, and transport proceeds slowly. The developing embryo reaches the uterus, it consists of a hollow ball of about 100 cells called a blastocyst. Trophoblast cells secrete proteolytic enzymes These act on the endometrium permitting penetration of blastocyst into endometrial stroma. These cells + maternal cells, form the placenta & membranes of pregnancy.  Some of the outer layer of blastocyst cells will become the chorion, an extraembryonic membrane that will enclose the embryo and form the placenta. The inner cell mass of the blastocyst will develop into the embryo and into three other extra-embryonic membranes. These membranes include the amnion, which secretes amniotic fluid in which the developing embryo floats; the allantois, which becomes part of the umbilical cord that links the embryo to the mother; and the yolk sac, which degenerates early in human development. Implantation of the blastocyst into the uterine wall normally takes place about seven days after fertilization. The blastocyst secretes enzymes that allow it to invade the endometrium, like a parasite burrowing into its host. Endometrial cells grow out around the blastocyst until it is completely engulfed. As the blastocyst continues dividing and becomes an embryo, cells that will become the placenta form finger-like chorionic villi that penetrate into the vascularized endometrium. Formation of placenta and amniotic sac During implantation, the endometrium undergoes changes This cellular growth and glycogen accumulation = decidual reaction Maternal cells in contact with the chorion = decidua basalis Decidual basalis + chorion = placenta Cytotrophoblast cells form chorionic villi which invade endometrial spiral arteries  Enzymes from the villi break down the walls of maternal blood vessels until the villi are surrounded by pools of maternal blood. The blood of the embryo and that of the mother do not mix, but nutrients, gases, and wastes exchange across the membranes of the villi. Many of these substances move by simple diffusion, but some, such as maternal antibodies, must be transported across the membrane. The placenta continues to grow during pregnancy until, by delivery, it is about 20 cm in diameter (the size of a small dinner plate). The placenta receives as much as 10% of the total maternal cardiac output. The tremendous blood flow to the placenta is one reason sudden, abnormal separation of the placenta from the uterine wall is a medical emergency Chorionic membranes Between day 7 and 12 the blastocyst becomes completely embedded in the endometrium Chorion is two cell thick - Inner cytotrophoblast - Outer syncytiotrophoblast The Inner cell mass also forms two layers - Ectoderm (nervous system and skin) - Endoderm (gut and its derivatives) The embryo is two cell thick separated from the cytotrophoblast by the amniotic cavity  Human Chorionic Gonadotropin As the blastocyst implants in the uterine wall and the placenta begins to form, the corpus luteum nears the end of its preprogramed 12-day life span. Unless the developing embryo sends a hormonal signal, the corpus luteum disintegrates, progesterone and oestrogen levels drop, and the embryo is flushed from the body along with the surface layers of endometrium during menstruation. The placenta secretes several hormones that prevent menstruation during pregnancy, including human chorionic gonadotropin, human chorionic somatomammotropin, oestrogen, and progesterone. The corpus luteum remains active during early pregnancy because of human chorionic gonadotropin (hCG), a peptide hormone secreted by the chorionic villi and developing placenta. Human chorionic gonadotropin is structurally related to LH, and it binds to LH receptors. Its most important function is to prevent involution of the corpus luteum at the end of the monthly female sexual cycle. Instead, it causes the corpus luteum to secrete even larger quantities of its sex hormones— progesterone and oestrogens—for the next few months hCG secretion is essential in the first 5 – 6 weeks when the placenta is immature Home pregnancy tests work by detecting elevated hCG levels in the woman's urine hCG declines by the 10th week of pregnancy Human chorionic gonadotropin production by the placenta peaks at three months of development, then diminishes. A second function of hCG is stimulation of testosterone production by the developing testes in male foetuses.  Diffusion of Oxygen Through the Placental Membrane. The haemoglobin of the foetus is mainly foetal haemoglobin, a type of haemoglobin synthesized in the foetus before birth. The dissolved oxygen in the blood of the large maternal sinuses passes into the foetal blood by simple diffusion, driven by an oxygen pressure gradient from the mother’s blood to the foetus’s blood. Near the end of pregnancy, the mean PO 2 of the mother’s blood in the placental sinuses is about 50 mm Hg, and the mean PO2 in the foetal blood after it becomes oxygenated in the placenta is about 30 mm Hg. Therefore, the mean pressure gradient for diffusion of oxygen through the placental membrane is about 20 mm Hg This means that at the low PO2 levels in foetal blood, the foetal haemoglobin can carry 20 to 50 percent more oxygen than maternal haemoglobin can.  Second, the haemoglobin concentration of foetal blood is about 50 percent greater than that of the mother; this is an even more important factor in enhancing the amount of oxygen transported to the foetal tissues. Third, the Bohr effect, which is explained in relation to the exchange of carbon dioxide and oxygen in the lung That is, haemoglobin can carry more oxygen at a low PCO 2 than it can at a high PCO2. The foetal blood entering the placenta carries large amounts of carbon dioxide, but much of this carbon dioxide diffuses from the foetal blood into the maternal blood. Loss of the carbon dioxide makes the foetal blood more alkaline, whereas the increased carbon dioxide in the maternal blood makes it more acidic. Carbon dioxide is continually formed in the tissues of the foetus in the same way that it is formed in maternal tissues, and the only means for excreting the carbon dioxide from the foetus is through the placenta into the mother’s blood.  Human Chorionic Somatomammotropin (hCS) Another peptide hormone produced by the placenta is human chorionic somatomammotropin (hCS), also called human placental lactogen (hPL). This hormone, structurally related to growth hormone and prolactin, was initially believed to be necessary for breast development during pregnancy and for milk production (lactation). hCS probably does contribute to lactation, but women who do not make hCS during pregnancy because of a genetic defect still have adequate breast development and milk production. A second role for hCS is alteration of the mother’s glucose and fatty acid metabolism to support foetal growth. Maternal glucose moves across the membranes of the placenta by facilitated diffusion and enters the foetal circulation. During pregnancy, about 4% of women develop gestational diabetes mellitus (GDM), with elevated blood glucose levels caused by insulin resistance, similar to type 2 diabetes.  Other metabolic substrates needed by the foetus diffuse into the foetal blood in the same manner as oxygen does. For instance, in the late stages of pregnancy, the foetus often uses as much glucose as the entire body of the mother uses. To provide this much glucose, the trophoblast cells lining the placental villi provide for facilitated diffusion of glucose through the placental membrane. That is, the glucose is transported by carrier molecules in the trophoblast cells of the membrane. The glucose level in foetal blood is 20 to 30 percent lower than that in maternal blood. Because of the high solubility of fatty acids in cell membranes, these also diffuse from the maternal blood into the foetal blood, but more slowly than glucose, so that glucose is used more easily by the foetus for nutrition. Also, such substances as ketone bodies and potassium, sodium, and chloride ions diffuse with relative ease from the maternal blood into the foetal blood.  Excretion of Waste Products Through the Placental Membrane In the same manner that carbon dioxide diffuses from the foetal blood into the maternal blood, other excretory products formed in the foetus also diffuse through the placental membrane into the maternal blood and are then excreted along with the excretory products of the mother. These include especially the nonprotein nitrogens such as urea, uric acid, and creatinine. The level of urea in foetal blood is only slightly greater than that in maternal blood because urea diffuses through the placental membrane with great ease. However, creatinine, which does not diffuse as easily, has a foetal blood concentration considerably higher than that in the mother’s blood. Therefore, excretion from the foetus depends mainly, if not entirely, on the diffusion gradients across the placental membrane and its permeability.  Disc shaped placenta is continuous with the smooth part of the chorion at its outer surface This part bulges into the uterine cavity Beneath the chorionic membrane is the amnion This envelops the embryo The embryo + umbilical cord are located within the fluid filled amniotic sac Amniotic fluid contains cells sloughed off from placenta, foetus and amniotic sac. Genetic abnormalities can be detected by aspiration of these cells This procedure is known as amniocentisis Downs syndrome Tay-Sachs It is usually performed at week 16 of pregnancy Amniotic Fluid and Its Formation Normally, the volume of amniotic fluid (the fluid inside the uterus in which the foetus floats) is between 500 millilitres and 1 litre, but it can be only a few millilitres or as much as several litres. Isotope studies of the rate of formation of amniotic fluid show that, on average, the water in amniotic fluid is replaced once every 3 hours and the electrolytes sodium and potassium are replaced an average of once every 15 hours. A large portion of the fluid is derived from renal excretion by the foetus. Likewise, a certain amount of absorption occurs by way of the gastrointestinal tract and lungs of the foetus.  placenta (5th week+) secretes human placental lactogen hormone (hPL) - breast development (also oestrogens & progesterone) - promotes foetal growth  foetal adrenals influence oestriol synthesis in placenta (oestriol dominant oestrogen during pregnancy) secrete cortisol - affects placental secretion oestrogens / progesterone - may initiate labour Effect of Human Chorionic Gonadotropin on the Foetal Testes. Human chorionic gonadotropin also exerts an interstitial cell–stimulating effect on the testes of the male foetus, resulting in the production of testosterone in male foetuses until the time of birth. This small secretion of testosterone during gestation is what causes the foetus to grow male sex organs instead of female organs. Near the end of pregnancy, the testosterone secreted by the foetal testes also causes the testes to descend into the scrotum. Secretion of Oestrogens by the Placenta Oestrogens secreted by the placenta are not synthesized de novo from basic substrates in the placenta. Instead, they are formed almost entirely from androgenic steroid compounds, dehydroepiandrosterone and 16-hydroxy- dehydroepiandrosterone, which are formed both in the mother’s adrenal glands and in the adrenal glands of the foetus. These weak androgens are transported by the blood to the placenta and converted by the trophoblast cells into Oestradiol, estrone, and estriol.  Progesterone causes decidual cells to develop in the uterine endometrium, and these cells play an important role in the nutrition of the early embryo. Progesterone decreases the contractility of the pregnant uterus, thus preventing uterine contractions from causing spontaneous abortion. Progesterone contributes to the development of the conceptus even before implantation because it specifically increases the secretions of the mother’s fallopian tubes and uterus to provide appropriate nutritive matter for the developing morula and blastocyst. The progesterone secreted during pregnancy helps the Oestrogen prepare the mother’s breasts for lactation Pituitary Secretion. The anterior pituitary gland of the mother enlarges at least 50 percent during pregnancy and increases its production of corticotropin, thyrotropin, and pro- lactin. Increased Corticosteroid Secretion. The rate of adrenocortical secretion of the glucocorticoids is moderately increased throughout pregnancy.  Stages of pregnancy The period of time from fertilization to birth (usually 9 months) is divided into trimesters Each is about three months long During pregnancy the zygote undergoes 40 to 44 rounds of mitosis These produce an infant containing trillions of specialized cells organized into tissues and organs.  The First Trimester Stages of pregnancy The three embryonic tissue layers form. Cellular differentiation begins to form organs during the third week After one month the embryo is 5 mm long and composed mostly of paired somite segments During the second month most of the major organ systems form, limb buds develop The embryo becomes a foetus by the seventh week Beginning the eighth week Stages of pregnancy - the sexually neutral fetus activates gene pathways for sex determination - testes are formed in XY foetuses - ovaries in XX fetuses - External genitalia develop. The Second Trimester The foetus increases in size Bony parts of the skeleton begin to form. Fetal movements can be felt by the mother. The Last Trimester Stages of pregnancy Foetus increases in size Circulatory and respiratory systems mature in preparation for air breathing Foetal growth uses a large amount of maternal protein and calcium intake Maternal antibodies pass to the foetus during the last month conferring temporary immunity  Labour and Birth Labour = powerful contractions of the uterus that are needed to expel the foetus Two agents stimulate these labour contractions Oxytocin (produced in the hypothalamus and released in the p pituitary) also produced by the uterus Prostaglandins (PG2α and PG2) COX-2 Labour can also be introduced artificially by injecting oxytocin or insertion of PG into the vagina as a suppository Activation of foetal adrenal cortex initiates labour Oestrogen is important in labour initiation by promoting uterine sensitivity to oxytocin The human placenta cannot synthesise oestrogen  Prostaglandins are produced in the uterus in response to oxytocin and CRH secretion. Prostaglandins are very effective at causing uterine muscle contractions at any time. They are the primary cause of menstrual cramps and have been used to induce abortion in early pregnancy. During labour and delivery, prostaglandins reinforce the uterine contractions induced by oxytocin The foetal adrenals have a cortex made up of two parts Outer part – secretes cortisol Inner part (foetal adrenal zone) – dehydroepiandrosterone sulfate (DHEAS) Foetal DHEAS travels to the placenta and is converted to oestrogen Rising oestrogen levels stimulate the uterus to 1.Produce receptors for oxytocin 2.Produce receptors for prostaglandins 3.Produce gap junctions between myometrial cells in the uterus - synchronise and coordinate uterine contractions (electrical synapses) Increase in PG and oxytocin receptors make the myometrium more sensitive to these agents The placenta secretes CRH which stimulates the anterior pituitary to secrete ACTH ACTH stimulates cortisol and DHEAS secretion by the foetal adrenals Cortisol secretion helps with foetal lung maturation It also stimulates CRH secretion by the placenta This results in a positive feedback loop that also results in DHEAS secretion The increased DHEAS is converted to oestriol Oestriol activates myometrium to be more sensitive to oxytocin and PG Following partuition oxytocin is important in Stages of labour maintaining muscle tone in the myometrium This reduces haemorrhaging from uterine arteries Promotes reduction in size of the uterus  Lactation Milk production is stimulated by prolactin from ant pituitary Prolactin secretion is controlled by prolactin- inhibiting hormone (PIH) secreted by the hypothalamus Increased oestrogen levels act on the mammary glands to block their stimulation by prolactin During pregnancy high oestrogen levels prepare the breasts for lactation but prevent secretion and action of prolactin  Although oestrogen and progesterone stimulate mammary development, they inhibit secretion of milk. Milk production is stimulated by prolactin from the anterior pituitary. Prolactin is an unusual pituitary hormone in that its secretion is primarily controlled by prolactin-inhibiting hormone (PIH) from the hypothalamus. Most evidence suggests that PIH is actually dopamine, an amine neurohormone related to epinephrine and norepinephrine. During the later stages of pregnancy, PIH secretion falls, and prolactin reaches levels 10 or more times those found in nonpregnant women. Prior to delivery, when oestrogen and progesterone are also high, the mammary glands produce only small amounts of a thin, low-fat secretion called colostrum (contains proteins, carbohydrates, fats, vitamins, minerals, and antibodies). After delivery, when oestrogen and progesterone decrease. The glands produce greater amounts of milk that contains 4% fat and substantial amounts of calcium  Proteins in colostrum and milk include maternal immunoglobulins, secreted into the duct and absorbed by the infant’s intestinal epithelium. This process transfers some of the mother’s immunity to the infant during its first weeks of life Pregnancy is not a requirement for lactation, however, and some women who have adopted babies have been successful in breast-feeding. The ejection of milk from the glands, known as the let-down reflex, requires the presence of oxytocin from the posterior pituitary. Prolactin is related to growth hormone and plays a role in other reproductive and nonreproductive processes. All non-nursing women and men have tonic prolactin secretion that exhibits a diurnal cycle, peaking during sleep. Prolactin is also involved in fertility in both males and females but this function is still being investigated.  Lactation When the placenta is expelled as the afterbirth oestrogen levels declines prolactin secretion increases Taking of oestrogen inhibit prolactin secretion Nursing maintains high prolactin levels via a neuroendocrine reflex Suckling activates sensory endings in the breast that relay impulses to the hypothalumus These inhibit PIH and may cause the secretion of prolactin releasing hormone Suckling also stimulate the reflex secretion of oxytocin Oxytocin stimulates contraction of uterus as well as the mammary glands (milk-ejection reflex) Placenta LACTATION development of breasts at puberty Oestrogen - major influence on breast development Prolactin - development of oestrogen receptors Oestrogen responsible for: · increased size / pigmentation of areola · deposition of fat & connective tissue within breasts · growth & branching of ducts Progesterone - acts only on the alveoli for full development of the breasts: oestrogens + progesterone + prolactin together with growth hormone thyroxine insulin cortisol  Increased Corticosteroid Secretion. The rate of adrenocortical secretion of the glucocorticoids is moderately increased throughout pregnancy. It is possible that these glucocorticoids help mobilize amino acids from the mother’s tissues so that these can be used for synthesis of tissues in the foetus. Pregnant women usually have about a twofold increase in the secretion of aldosterone, reaching a peak at the end of gestation. This, along with the actions of Oestrogens, causes a tendency for even a normal pregnant woman to reabsorb excess sodium from her renal tubules and, therefore, to retain fluid, occasionally leading to pregnancy-induced hypertension Increased Thyroid Gland Secretion. The mother’s thyroid gland ordinarily enlarges up to 50 percent during pregnancy and increases its production of thyroxine a corresponding amount. The increased thyroxine production is caused at least partly by a thyrotropic effect of human chorionic gonadotropin secreted by the placenta and by small quantities of a specific thyroid- stimulating hormone, human chorionic thyrotropin, also secreted by the placenta.  Increased Parathyroid Gland Secretion. The mother’s parathyroid glands usually enlarge during pregnancy; this is especially true if the mother is on a calcium- deficient diet. Enlargement of these glands causes calcium absorption from the mother’s bones, thereby maintaining normal calcium ion concentration in the mother’s extracellular fluid even while the foetus removes calcium to ossify its own bones.  Response of the Mother’s Body to Pregnancy Weight Gain in the Pregnant Woman The average weight gain during pregnancy is about 25 to 35 pounds (10-15 kg’s), with most of this gain occurring during the last two trimesters. Of this, about 8 pounds is foetus and 4 pounds is amniotic fluid, placenta, and foetal membranes. The uterus increases about 3 pounds and the breasts another 2 pounds, still leaving an average weight increase of 8 to 18 pounds. About 5 pounds of this is extra fluid in the blood and extra- cellular fluid, and the remaining 3 to 13 pounds is generally fat accumulation. The extra fluid is excreted in the urine during the first few days after birth, that is, after loss of the fluid- retaining hormones from the placenta. Metabolism During Pregnancy As a consequence of the increased secretion of many hormones during pregnancy, including thyroxine, adrenocortical hormones, and the sex hormones, the basal metabolic rate of the pregnant woman increases about 15 percent during the latter half of pregnancy. As a result, she frequently has sensations of becoming overheated.  Nutrition During Pregnancy By far the greatest growth of the foetus occurs during the last trimester of pregnancy; its weight almost doubles during the last 2 months of pregnancy. Ordinarily, the mother does not absorb sufficient protein, calcium, phosphates, and iron from her diet during the last months of pregnancy to supply these extra needs of the foetus. However, anticipating these extra needs, the mother’s body has already been storing these substances—some in the placenta, but most in the normal storage depots of the mother. Changes in the Maternal Circulatory System During Pregnancy Blood Flow Through the Placenta, and Maternal Cardiac Output Increases during Pregnancy. About 625 millilitres of blood flows through the maternal circulation of the placenta each minute during the last month of pregnancy. This, plus the general increase in the mother’s metabolism, increases the mother’s cardiac output to 30 to 40 percent above normal by the 27th week of pregnancy; then, for reasons unexplained, the cardiac output falls to only a little above normal during the last 8 weeks of pregnancy, despite the high uterine blood flow.  Maternal Blood Volume Increases During Pregnancy. The maternal blood volume shortly before term is about 30 percent above normal. This increase occurs mainly during the latter half of pregnancy. The cause of the increased volume is likely due, at least in part, to aldosterone and oestrogens, which are greatly increased in pregnancy, and to increased fluid retention by the kidneys. Also, the bone marrow becomes increasingly active and produces extra red blood cells to go with the excess fluid volume. Therefore, at the time of birth of the baby, the mother has about 1 to 2 litres of extra blood in her circulatory system. Only about one fourth of this amount is normally lost through bleeding during delivery of the baby, thereby allowing a considerable safety factor for the mother. Maternal Respiration Increases During Pregnancy Because of the increased basal metabolic rate of a pregnant woman and because of her greater size, the total amount of oxygen used by the mother shortly before birth of the baby is about 20 percent above normal and a commensurate amount of carbon dioxide is formed. These effects cause the mother’s minute ventilation to increase. It is also believed that the high levels of progesterone during pregnancy increase the minute ventilation even more, because progesterone increases the respiratory centre’s sensitivity to carbon dioxide. The net result is an increase in minute ventilation of about 50 percent and a decrease in arterial PCO2 to several millimetres of mercury below that in a nonpregnant woman. Simultaneously, the growing uterus presses upward against the abdominal contents, which press upward against the diaphragm, so the total excursion of the diaphragm is decreased. Consequently, the respiratory rate is increased to maintain the extra ventilation. Maternal Kidney Function During Pregnancy The rate of urine formation by a pregnant woman is usually slightly increased because of increased fluid intake and increased load of excretory products. The renal tubules’ reabsorptive capacity for sodium, chloride, and water is increased as much as 50 percent as a consequence of increased production of salt and water retaining hormones, especially steroid hormones by the placenta and adrenal cortex. Second, the renal blood flow and glomerular filtration rate increase up to 50 percent during normal pregnancy due to renal vasodilation. Although the mechanisms that cause renal vasodilation in pregnancy are still unclear, some studies suggest that increased levels of nitric oxide or the ovarian hormone relaxin may contribute to these changes. The increased glomerular filtration rate likely occurs, at least in part, as a compensation for increased tubular reabsorption of salt and water. Thus, the normal pregnant woman ordinarily accumulates only about 5 pounds of extra water and salt.  MENOPAUSE 40 – 50 yrs: cycles  irregular/ cease hot flushes, irritability, fatigue, anxiety, emotionality oestrogen output decreases.. due follicle depletion over reproductive yrs lack eostrogens  osteoporosis risk Ca2+ / phosphor lost from bones  weaken / fracture- prone  compression of vertebrae (loss of height) ± absence ovarian steroids - symptoms oft Tx w oestrogens circulating [LH / FSH] increase.. continuous secretion, not cyclical