2024 Fall MBS Repro 2 PDF

Pathophysiology 5160 Reproduction 2 Dr. Maiyon Park CUSM - MBS COPYRIGHT NOTICE All materials found on CUSM’s course and project sites may be subject to copyright protection, and may be restri...

Pathophysiology 5160 Reproduction 2 Dr. Maiyon Park CUSM - MBS COPYRIGHT NOTICE All materials found on CUSM’s course and project sites may be subject to copyright protection, and may be restricted from further dissemination, retention or copying. DISCLOSURE I have no financial relationship with a commercial entity producing health-care related products and/or services.  Session Learning Outcomes (SLOs) Students are able to describe the followings 1. Male reproductive system a. Testes and Spermatogenesis b. Storage and ejaculation of sperm, capacitation of sperm for fertilization c. Male accessory reproductive glands d. Testicle descending and Cryptorchism (Cryptorchidism) 2. Female reproductive system a. Female reproductive physiology b. Oogenesis and Stages of the development of ovarian follicles c. Attrition of oocytes d. Synthesis and Secretion of Estrogen and Progesterone 2  SLO 1a: Structure and Function of Testes Testes function in Spermatogenesis & Testosterone Secretion Occupy scrotum lying outside body cavity It is 35-36°C, a few below body Temp that is essential for spermatogenesis. It is due to counter-current layout of testicular arteries & veins for heat exchange Seminiferous tubules make up ~80% of the adult testis are convoluted loops arranged in lobules & connective tissue where sperms are produced through spermatogenesis Cell types of seminiferous tubule epithelium - Spermatogonia (2n2c) are undifferentiated male germ cells - Spermatocytes (2n2c) are cells derived from spermatogonia by mitosis that are in process of becoming mature sperm - Spermatids are haploid (1n1c) cells formed by meiotic division. Spermatids mature and develop into spermatozoa or sperms by the process of spermiogenesis, the final stage of spermatogenesis.  SLO 1a: Spermatogenesis (producing mature spermatozoa) 1. Multiplication phase Spermatogonia are undifferentiated, diploid (2n2C, 46) stem cells at basal lamina Spermatogonia proliferate by Mitotic division 2. Growth phase One of daughter spermatogonia grows & enters Meiosis I & becomes primary spermatocyte that is in the prophase of Meiosis I (2n2C, 46) Primary spermatocyte becomes secondary spermatocytes (1n1C, haploid) by the completion of Meiosis I Each secondary spermatocyte enters Meiosis II & produce 2 haploid spermatids (1n1C, 23) 4 spermatids (1n1C, haploid, 23) are produced from a primary spermatocyte 3. Maturation phase (Spermiogenesis) Spermatids differentiate into spermatozoa (sperm, 1n1c) with flagellum to swim  SLO 1b: Storage of sperm, ejaculation, and fertilization Sperms leave testes via epididymis, primary location for maturation & storage & are viable in epididymis for several months During sexual arousal, contractions of smooth muscle around ducts advance sperm through epididymis At ejaculation, sperms are expelled into vas deferens to seminal vesicle to prostate gland to urethra and to penis Ampulla of vas deferens secretes fluid rich in citrate & fructose & is additional storage & nourishing area for the ejaculated sperms Sertoli cells lining seminiferous tubules support Spermatogenesis 1. Provide nutrients to differentiating sperms that are isolated from blood stream 2. Form tight junctions to create blood-testis barrier that has selective permeability to allow testosterone to cross but prohibit noxious substances that damage sperm 3. Secrete an aqueous fluid into lumen of seminiferous tubules to transport sperm thru the tubules into the epididymis ~15 million sperms per milliliter is normal count  SLO 1b: Capacitation, Acrosomal Reaction and Fertilization Ejaculated sperm cannot immediately fertilize ovum As sperms travel through female reproductive system to the fallopian tubes, where the oocyte is located, a series of transformations occur Sperms reside in female reproductive tract for 10 hrs for Capacitation. Sperm capacitation is the process that allows sperm to acquire ability to fertilize egg During Capacitation, sperms become free from adherent seminal plasma proteins & there is reorganization of plasma membrane proteins & lipids Calcium influx into tail of the sperm, increasing cAMP & decreasing intracellular pH The motility & motion of sperm becomes "whip like" Capacitation results in acrosomal reaction, fusion of acrosomal membrane with outer sperm membrane Fusion creates pores and hydrolytic & proteolytic enzymes escape from acrosome, creating a path for sperm to penetrate protective coverings of ovum 6 SLO 1c: Male Reproductive accessory organs- Seminal vesicle & Prostate gland Male accessory glands secrete 90% of liquid portion of semen & the rest is sperm Seminal vesicles secrete alkaline viscous fluid (60% of semen) containing fructose, citrate & prostaglandins that provide nutrition for ejaculated sperm. Prostate Glands Secret milky aqueous fluid that contains citrate, calcium, prostaglandins & enzymes Slightly alkaline secretion increases sperm motility & aids fertilization by neutralizing acidic secretions from vas deferens & the acidity of vagina Prostaglandins react with cervical mucus for sperm penetration & induce peristaltic contractions to propel sperm into female reproductive tract (uterus & fallopian tubes) Benign Prostatic Hyperplasia (BPH) Common condition in men over age 50 (20% in over 40, up to 70% by 60, and 90% by age 70) Hyperplasia of both Glands & Stroma DHT function in growth of prostate (5-alpha reductase) and no BPH in castration If significantly enlarged, prostate compresses urethral canal leading to urinary obstruction & urinary incontinence (inability to control urination) 7  SLO 1d. Testicle Descend and Cryptorchidism Most of the time, a boy's testicles descend by the time he is 9 months old. Testicles descend into scrotum through the inguinal ring Undescended testicles are common in infants who are born early If not descended, it is Cryptorchidism Cryptorchidism (Cryptorchism) Incomplete descend of testicles into scrotum Uni- or bilateral cryptorchidism is present in ~4% of prepubertal boys Cryptorchid testis is found along normal path of descend, the abdomen, inguinal canal, and prescrotal locations Malformed or elongated epididymis SUMMARY of Male Reproductive System  SLO 2a: Female Reproductive Physiology Female reproductive system includes ovaries (female gonad), uterus, fallopian tubes, cervix, and vagina,,,*don’t confuse with internal/external genital tract Parts Functions produces egg (ova) & female hormones, Estrogen & Ovary Progesterone Fallopian tube Catches the egg from the ovary and transports it to (Oviduct) the uterus, site of Fertilization Site of Implantation, holds the developing embryo. Uterus Has a lining-endometrium that is enriched with blood vessels to nourish embryo & forms placenta Cervix Connects the uterus to vagina. Produces mucus for sperm movement Vagina Allows entry of sperm and exit of baby at birth Each adult ovary is attached to the uterus (womb) by ligaments Ovaries (equivalent to testes in male) Ovarian arteries, veins, Produce egg (Ova) through Oogenesis lymphatic vessels & nerves run Produce female sex hormones, Estrogens & Progesterone thru these ligaments 10 SLO 2b: Oogenesis & Follicle Development of Female Reproduction Oogenesis occurs in the Ovary Oogenesis is process for the development of mature oocytes (haploid gametes) that is capable of fertilization by sperm The creation of eggs (genesis means creation) Egg is ovum (singular), ova (plural) Female germ cells in ovaries produce primordial germ cells (PGC), which then undergo mitosis to form oogonia The first phase of egg development begins in female fetus & Oogonia become primary oocytes of primordial follicles (both diploid), which is completed by the end of the 3rd month of fetal development Primary oocytes of primordial follicles begin meiosis but are arrested in prophase of meiosis I The final phase of egg development is completed only if egg is fertilized by a sperm SLO 2b: Ovaries & Follicle Development for Female Reproduction Cortex of ovary is outer, largest zone & lined by germinal epithelium. It contains all of oocytes enclosed in follicle. Medulla of ovary is middle zone & it has mixture of cell types Hilum of ovary is inner zone, through which blood vessels & lymphatics passes Ovarian follicles Are functional unit of ovaries & consist of an oocyte surrounded by layers of follicular or granulosa cells Inactive primordial follicles are formed during fetal life that consist of primary oocyte enclosed by a single layer of flattened follicular cells Primary oocytes of primordial follicle are arrested in prophase I of first meiotic division (2n) for 13–50 yrs, the shortest at 1st ovulation & the longest at menopause 12  SLO 2b: Follicle Development for Female Reproduction Activation of Fetal Primordial follicle to Primary follicle Primordial follicle develops to active Primary follicle that may take 13-50 years (from the onset of puberty to menopause) There is change from Flattened to Cuboidal follicular epithelial cells Granulosa cells proliferate, protective zona pellucida is formed & follicle grows to 2⁰ follicle by the completion of 1st meiosis No follicle progresses beyond 2⁰ follicle in prepubertal ovaries During Puberty Granulosa & theca cells of secondary follicle continue to grow 2nd meiotic division starts, and Graafian follicle is formed with secondary (2⁰) oocyte. Unless fertilized, the secondary (2⁰) oocyte is arrested in the metaphase II of second meiosis Each menstrual cycle, ~20 of 2⁰ follicles enter this process but only one 2⁰ follicle becomes Graafian follicle Graafian follicle formation from 2⁰ follicle takes 70-85 days  SLO 2b: Follicle Development for Female Reproduction At Final stage, a single Graafian follicle becomes dominant & the rest of follicles regress It occurs 5-7 days after menstruation (most rapid) & dominant follicle grows On 14th of 28- day menstrual cycle, ovulation occurs, dominant follicle ruptures & releases its 2⁰ oocyte into peritoneal cavity. 2⁰ oocyte enters the fallopian tube If fertilization occurs in fallopian tube, the 2nd meiotic division is completed. Haploid ovum with 23 chromosomes is produced The nuclei of the sperm cell and the ovum unite and form a diploid (2n) zygote After ovulation, residual elements of ruptured dominant follicle form Corpus Luteum Corpus luteum has granulosa cells, theca cells, capillaries & fibroblasts If fertilization does occur, corpus luteum will release hormones for implantation & maintenance of the zygote until the placenta releases hormones later in pregnancy If fertilization does not occur, corpus luteum regresses during next 14 days of second half of menstrual cycle, & is replaced by a scar called the corpus albicans  SLO 2c: Unequal Cytokinesis during Oogenesis Oogonia (2n) are formed via mitosis During fetal development, Meiosis I begins, the primary oocytes (2n) are formed and arrested at Prophase I of first Meiosis After puberty, primary oocytes complete Meiosis I and produces a secondary oocyte and a first polar body The first polar body may or may not divide again The secondary oocyte begins Meiosis II, which is arrested in Metaphase II of the second Meiosis One secondary oocyte is released during ovulation Sperms penetrate the egg and Meiosis II resumes. Upon completion of 2nd meiosis, the haploid ovum and a polar body are produced After capacitation, the nuclei of the sperm cell and the ovum unite and form a diploid (2n)- zygote  SLO 2c: Attrition of Oocytes in Female Lifetime Attrition of oocytes By 20–24 wGA, ~7 million oogonia are present but most will degenerate during the next 2 months Some oogonia differentiate into primordial follicle with primary oocyte (arrested in prophase of meiosis I) Meiotic process continues until ~6 months after birth and at that point all oogonia have become the primary oocytes At birth, only about 2 million oocytes remain and No primary oocytes will be produced during female's lifetime. About 400,000 oocytes remain at the beginning of puberty Meiosis resumes at the beginning of the first menstrual cycle and produces ovulatory oocyte, one oocyte at a time Only 400–500 oocytes (at most) will be released during woman's reproductive years. By menopause (marks the end of the reproductive period), only a few oocytes remain Males continuously produce spermatogonia & spermatocytes. However, females do not produce new oogonia & function from a declining pool of oocytes.  SLO 2d: Steroid hormone production in Ovary Steroid Hormones of Ovary The ovarian steroid hormones support the development of ova locally within the ovaries Systemically, ovarian steroid hormones act on many target tissues, uterus, breast & bone Primary follicles contain primary oocyte & produce Estrogen Secondary follicles contain secondary oocyte & produce Estrogen & Progesterone Corpus luteum produces mainly Progesterone LH stimulates the cholesterol desmolase in theca cells and produces androgens, progesterone & androstenedione FSH stimulates the aromatase in granulosa cells and produce the female sex hormone, estrogen 17β-estradiol synthesis Androstenedione diffuses from theca cells to nearby granulosa cells that contain 17β-HSD & Aromatase In granulosa cells, androstenedione is converted to testosterone (17β-HSD) Testosterone is converted to 17β-estradiol (aromatase) SUMMARY of Parts and Functions of Female Reproductive System