BIOL 221 - Female Reproductive System PDF

BIOL 221 – Female Reproductive System Cristofre Martin Department of Biochemistry St. George’s University  Lecture Objectives List the functions of the female reproductive system List the structures and functions of the female reproductive system. Describe the process of oogenesi...

BIOL 221 – Female Reproductive System Cristofre Martin Department of Biochemistry St. George’s University  Lecture Objectives List the functions of the female reproductive system List the structures and functions of the female reproductive system. Describe the process of oogenesis and follicle development. Describe the endometrium of the uterus and the changes that occur during the menstrual cycle. Identify the medulla and cortex of the ovary, the location where ovarian follicles develop. List the various stages of development of the oocyte, describing the changes that occur. Explain the path of an oocyte after ovulation, and its fate if it is fertilized Define ectopic pregnancy Describe the role of the different hormones during follicle development Describe the hormonal changes that occur during the menstrual cycle Define endometriosis Describe the development of the placenta and the maternal/fetal blood supply Describe the mammary glands Describe the external female genitalia  Function of the Female Reproductive System Production of gametes (oocytes or eggs) Provides site for fertilization of oocytes Preparation for and support of developing embryo and fetus Maintains, nourishes developing fetus and removes waste products Generates cyclical changes: Menstrual cycle  Vagina Tubular, muscular organ Extends from the uterus to outside the body Muscular Rugae (folds) enable expansions to receive erect penis and passage for delivery of children (birth canal) Provide outlet for uterine secretions and menstrual cycle Vaginal Wall: Adventitia (Outer Fibrous Layer) Muscularis (Middle Muscular Layer) Mucosa (Inner Mucosal Layer)  Fallopian Tube (Oviduct) Open ended tube leading from the uterus towards the ovary Oviduct is composed of a mucosa layer containing columnar epithelium and a muscularis layer The terminal ampulla possess fimbriae that are ciliated Cilia beat rapidly providing a current to direct ovulated eggs into the through the oviduct The oviduct is the location where fertilization typically Mucosa layer Cross section showing ciliated occurs oviduct columnar epithelium  Hollow, thick-walled organ located in the pelvis Structure of the Uterus anterior to the rectum and posterior to the bladder Receives, retains and nourishes the developing embryo The entrance to the uterus from the vagina is the cervix The wall of the uterus is composed of three different layers: Perimetrium: outer serous membrane Myometrium: middle middle Endometrium: inner mucosal lining Endometrium consists of 2 layers: 1.stratum basalis, a permanent basal layer 2.stratum functionalis, the luminal layer. This layer alters with the menstrual cycle, in preparation for the embedding of an embryo. It is shed if no embryo implantation occurs. Uterine glands secrete substances for embryo and extraembryonic tissue survival.  Structure of the Ovary Held in place by mesentery and ligaments: Broad ligament Suspensory ligament of the ovary Ovarian ligament Innervation: Sympathetic and parasympathetic Each of the paired ovaries is enclosed in a dense irregular connective tissue capsule, the tunica albuginea. Beneath this capsule is the cortex, which contains the oocytes within ovarian follicles. The innermost medulla consists of loose connective tissue, blood vessels, lymphatics and nerves.  Oogenesis In the human female, ovarian follicles develop about 105 days after conception. By birth, the ovaries contain about 2,000,000 oocytes. All are in prophase I of The maximum number of meiosis, where they will oocytes in a human female remain until individual occurs prior to when you are oocytes begin to mature at born. puberty. Rapid decline in viable oocytes after 35 years of age.  Germinal Tunica Ovarian Primordial follicles epithelium albuginea cortex Ovarian follicles consist of an oocyte surrounded by a single layer of follicular cells. Later in development, the follicular cells multiply into several layers, known as granulosa cells. Granulosa cells nourish the oocyte and begin to secrete estradiol as the follicle enlarges. Theca folliculi Zona pellucida 10 oocyte granulosa cells Primary follicle The Ovarian cortex The phases of an ovarian follicle a. 1ooocyte in follicle 1. As the 1o oocyte develops, the follicle’s granulosa cells multiply. 2. During the next phase, a cavity b. develops within the mass of Growing follicle granulosa cells, filling with follicular fluid. 3. The 1st meiotic division occurs Corona radiata during this time. Cells surrounding c. the 2ndary oocyte are corona radiata. This is now a Graafian follicle. Graafian follicle  Ruptured follicle The Graafian follicle ruptures, releasing the 2ndary oocyte and the corona radiata. Ovulated secondary oocyte The corpus luteum is the remnant of an ovulated mature follicle. It produces estradiol, relaxin, progesterone and inhibin. If implantation does not occur the Corpus luteum Corpus luteum degenerates into fibrous tissue, the corpus albicans. Degenerating corpus luteum These images are of human ovulation in progress. They were captured in 2008 by Dr Jacques Donnez by chance during a routine hysterectomy. These were the very first images ever taken of human ovulation.  (24-72 hrs) (4 days) (6-7 days) Before ovulation, fimbriae, ciliated cells at the end of the oviduct, move closer to the ovary. Their movement sweeps the oocyte into the oviduct. Once an oocyte is released from an ovary, it is transported via a fallopian tube (oviduct) to the uterus. If fertilization occurs, it will happen in the ampulla of the oviduct, and the embryo develops in the uterus.  Ectopic Pregnancy Occasionally, an oocyte remains in the pelvic cavity or fallopian tube and is fertilized and begins development there. This is called an ectopic pregnancy.  Menstrual cycle In mammals, the uterus prepares cyclically for implantation of an embryo. The entire cycle, from the first increase of the uterine lining until it is shed, is known as a menstrual cycle. In humans the average length of the menstrual cycle is 28 days.  Hormones of the menstrual cycle GnRH, gonadotropic releasing hormone, is released by the hypothalamus and travels to the anterior pituitary gland, stimulating the release of FSH, follicle stimulating hormone, and LH, luteinizing hormone. FSH stimulates growth of an ovarian follicle. Estradiol is the primary hormone released by the ovarian follicle. Estradiol, progesterone, inhibin and relaxin are all released by the corpus luteum.  Hormones continued An increase in the combination of estradiol + progesterone inhibits GnRH and therefore, LH and FSH. Progesterone acts synergistically with estradiol to prepare the uterus for implantation. Slight increase in the level of estradiol inhibits FSH and LH. High levels of estradiol stimulate GnRH, and then FSH, and a dramatic burst of LH. Hormonal control of Oocyte Maturation & Ovulation (Mammals): HYPOTHALAMUS GnRH (gonadotropin- releasing hormone) PITUITARY FSH FOLLICLE CELLS LH pituitary FSH release Estrogen Follicle growth FSH receptors on follicle cells Continued follicle growth (1o oocyte) Estrogen HYPOTHALAMUS GnRH PITUITARY GRAAFIAN FOLLICLE LH surge 1) Completion of meiosis I 2) ovulation Cont’d on next slide  1) Completion of meiosis I 2) Ovulation 20 OOCYTE (arrested in metaphase II) + 1st polar body + corona radiata cells Fertilization Completion of meiosis II (+ 2nd polar body extrusion) Follicular phase: days 1-14 Hypothalamus Inhib: estradiol + progesterone – + GnRH Stim: high estradiol Day 1: – Anterior pituitary Inhib: mod estradiol FSH LH A slow increase in FSH starts follicle Pituitary maturation. gonadotropins in blood LH The follicle slowly enlarges, forming FSH a swelling on the ovary wall. Usually, FSH, LH stimulate follicle to grow LH surge triggers ovulation Ovarian cycle several follicles begin maturation; Growing Graafian Corpus Degenerating one develops faster than the others, follicle follicle luteum corpus luteum Follicular phase Ovulation Luteal phase secreting estradiol and inhibin. Progesterone The slight increase in estradiol Ovarian hormones in Peak causes blood LH surge Estradiol decreases FSH production, halting 9 Progest. + estr. promo development of other follicles. endometrial thickenin Occasionally, two follicles achieve Uterine (menstrual) cycle codominance. If both are fertilized → fraternal 0 | 5 | 10 | 14 15 20 25 28 twins.  Inhib:estradiol + progesterone – Hypothalamus + Stim: high estradiol GnRH As the primary follicle grows, – Anterior pituitary Inhib: mod estradiol FSH LH estradiol production increases Pituitary rapidly, stimulating release of GnRH gonadotropins in blood LH and causing a burst of LH at mid cycle. FSH, LH stimulate FSH LH surge triggers follicle to grow ovulation Day 14: the sudden surge of LH Ovarian cycle causes the follicle release the Growing follicle Maturing follicle Corpus luteum Degenerating corpus luteum Follicular phase Ovulation Luteal phase secondary oocyte. Progesterone Ovarian hormones in Peak causes blood LH surge Estradiol 9 Progest. + estr. promo endometrial thickenin Uterine (menstrual) cycle | | | | | 0 | 5 | 10 | 14 15 20 25 28  Inhib:estradiol + progesterone – Hypothalamus + Stim: high estradiol GnRH Luteal phase Days14-28 – Anterior pituitary FSH LH Inhib: mod estradiol After ovulation, LH stimulates the Pituitary gonadotropins empty follicle to develop into corpus in blood LH luteum. FSH FSH, LH stimulate LH surge triggers follicle to grow ovulation The corpus luteum secretes Ovarian cycle estradiol, progesterone, relaxin and Growing follicle Maturing Corpus Degenerating follicle luteum corpus luteum inhibin. Follicular phase Ovulation Luteal phase Estradiol and progesterone act Ovarian hormones in Peak causes Progesterone LH surge synergistically to support blood Estradiol development of the uterine lining for 9 Progest. + estr. promo possible implantation. endometrial thickenin Uterine (menstrual) cycle | | | | | 0 | 5 | 10 | 14 15 20 25 28 Menstrual phase Inhib:estradiol + progesterone – Hypothalamus The combination of estradiol and + Stim: high estradiol GnRH Anterior pituitary Inhib: mod estradiol progesterone inhibit GnRH secretion, and – FSH LH therefore, LH and FSH. Pituitary gonadotropins Decreased LH eventually causes atrophy of in blood LH the corpus luteum, decreasing estradiol and FSH progesterone. FSH, LH stimulate LH surge triggers follicle to grow ovulation This causes breakdown of the uterine Ovarian cycle lining→menstruation. Growing follicle Maturing Corpus Degenerating follicle luteum corpus luteum Follicular phase Ovulation Luteal phase If the oocyte is fertilized, regression of the corpus luteum is averted because embryonic Progesterone Ovarian hormones in Peak causes tissue is producing chorionic gonadotropic blood LH surge hormone. 9 Estradiol The maintenance of the corpus luteum Progest. + estr. promo endometrial thickenin continues the level of estradiol and Uterine (menstrual) cycle progesterone, preventing breakdown of the endometrium. | | | | | 0 | 5 | 10 | 14 15 20 25 28  Uterine (menstrual) cycle Endometrium Menstrual flow phase Proliferative phase Secretory phase Days 28 | 10 14 15 20 25 0 5 The Endometrial Phases: Menstrual phase: LH decreases. Corpus luteum atrophies, decreasing estradiol and progesterone. The uterine lining breaks down. Day 1-5. Proliferative phase: as granulosa cells secrete increasing amounts of estradiol, the lining grows. Day 6-14. Secretory phase: increased estradiol and progesterone cause the endometrium to become more vascular and glandular, and encourage glycogen deposition. Day 15-28.  Endometriosus Normally, the entire functional layer of the endometrium is sloughed off, and leaves the uterus via the cervix. Occasionally, some of the endometrium will relocate in the abdomen, attaching to an organ and tapping into the neighboring blood supply. Each month, under the stimulus of hormones, it will increase and then breakdown. Day 7-9: Some trophectodermal cells fuse to form syncytia. These syncytia proliferate and invade the endometrial extracellular matrix. The former trophectodermal cells, now called cytotrophoblastic cells, migrate between the syncytia followed by the fetal stroma. This will lead to the formation of the placental villi. Fetal and Maternal Blood Circulation FETAL MATERNAL The placenta is derived from the embryo and facilitate oxygen, nutrient and waste exchange. It begins to function around 5 weeks of development. The umbilical veins and arteries enter the capillary bed of the chorionic villus while maternal blood forms pools between the chorionic villus. Exchange is similar to that of a lung. Additionally since fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin – oxygen is stripped out from the maternal blood pools.  Maternal Maternal arteries veins Placenta Maternal portion of placenta Umbilical cord Chorionic villus, containing fetal capillaries Fetal portion of Maternal blood placenta pools (chorion) Uterus Umbilical Fetal arteriole arteries Fetal venule Umbilical cord Umbilical vein  Reasons for Spontaneous Abortion and Miscarriage: 1. Implantation of the embryo does not occur 2. Insufficient amounts of HCG to prevent continuation of menstrual cycle 3. Early developmental defects prevents embryonic development from proceeding 4. Insufficient amounts of progesterone production result in thinning and break down of the uterine lining 5. Abnormal implantation 6. Abnormal placenta Estimates are that 70% of fertilized eggs get miscarried, and about 30% of implanted eggs miscarry.  Birth control Sperm live a maximum of 72 hours; oocytes:12-24 hours. Therefore, intercourse must occur within 72 hrs pre-, or 24 hrs post- ovulation to conceive. Time barrier: rhythm. Mechanical barriers: condoms, diaphragms. Chemical barriers: creams, foams, spermicidal jellies. Not reliable alone. Often used with a diaphragm. Oral contraceptives: synthetic estrogen and progesterone-like substances. They disrupt the normal pattern of GnRH release, preventing the LH surge needed for ovulation. Very effective, but possible side effects ( high blood pressure, nausea, etc.)  Injectable contraception: intramuscular injection of a progesterone derivative prevents ovulation for 3 mos. Contraceptive implants: surgically inserted, the progesterone is released slowly and prevents ovulation. It is effective for up to 5 years, and effects halt upon removal. Intrauterine device (IUD): placed in the cervix uterine cavity to interfere with blocks sperm movement and implantation by thickening cervical mucous. Some also secrete progestogen. Surgical methods: vasectomy and tubal ligation. RU486 (‘morning after” pill): binds to progesterone receptors; uterine proliferation ceases.  Hormone summary GnRH: release of LH and FSH LH: sudden surge causes ovulation – a moderate amount will maintain the corpus luteum – decreased LH causes atrophy of the corpus luteum FSH: slight increase causes follicle to begin maturation. – Maturation increases the amount of estradiol and inhibin. Estradiol: slight increase inhibits GnRH, LH, FSH-this halts development of most follicles. – High levels stimulate GnRH, FSH and particularly LH, which is released in a surge – Estradiol and progesterone combined inhibit release of GnRH, LH, FSH Progesterone: acts with estradiol to prepare uterus for implantation Inhibin: high levels inhibit LH and FSH Relaxin: remodels collagen, increasing elasticity of pelvic joints and tissues of the birth canal. Note: if fertilization occurs, within 12 days the chorion of the developing embryo will be producing chorionic gonadotropic hormone, maintaining the corpus luteum.  Mammary glands (breasts) Modified sweat glands Function typically only in lactating female Produce milk to feed the baby Respond to hormonal stimulation (primarily prolactin and oxytocin from the pituitary) Nipple surrounded by pigmented ring of skin, the areola 34  Mammary glands consist of 15-25 lobes Each a distinct compound alveolar gland opening at the nipple Separated by adipose and suspensory ligaments Smaller lobules composed of tiny alveoli or acini – Like bunches of grapes – Walls: simple cuboidal epithelium of milk-secreting cells – Don’t develop until half-way through pregnancy (ducts grow during puberty) Milk passes from alveoli through progressively larger ducts – Largest: lactiferous ducts, collect milk into sinuses 35  External female genitalia (vulva) Mons pubis: fatty pad over pubic symphysis, with hair after puberty Labia majora: long fatty hair-covered skin folds Labia minora: thin, hairless, folds enclosing vestibule Vestibule: houses external openings of urethra and vagina – Urethra is anterior (drains urine from bladder) – Baby comes out through vagina (vaginal orifice in pic) Clitoris: anterior, homolog of penis (sensitive erectile tissue) 36