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Lecture 15

ANP1107 Lecture 15: Lecture 15

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University of Ottawa
Anatomy and Physiology
Jackie Carnegie

Anatomy and Physiology of the Female Reproductive Systems • Anatomy of the Ovaries The reproductive role of the female is much more complex than that of a male. Not only must she produce gametes, but her body must prepare to nurture a developing fetus for approximately 9 months. -internal genitalia: ovaries and duct system (mostly located in pelvic cavity) -accessory ducts: uterine tubes (oviducts), uterus, vagina -external genitalia: vulva The paired ovaries flank the uterus, each ovary is held in place by several ligaments in the peritoneal cavity. The ovarian ligaments anchors the ovary medially to the uterus, the suspensory ligament anchors it lateral to the pelvic wall, and the mesovarium suspends it in between. The suspensory and mesovarium ligaments are part of the broad ligament that supports the uterine tubes, uterus, and vagina. The ovaries are served by the ovarian arteries, branches of the abdominal aorta and by the ovarian branch of the uterine arteries. Like each testis, each ovary is surrounded externally by tunica albuginea, which is in turn covered externally by a layer of cuboidal epithelial cells called the germinal epithelium. The ovary has an outer cortex, which houses the forming gametes (follicles at all stages of development). Each follicle consists of an immature egg, called an oocyte. The surrounding cells are called follicle cells (single layer) and granulosa cells when more than one layer is present. Theca cells are the endocrine cells associated with ovarian follicles that play an essential role in fertility by producing the androgen substrate required for ovarian estrogen biosynthesis. The corpus lute is formed from an ovulated follicle each month. • Anatomy of the Oviducts Unlike the male duct system, which is continuous with the tubules of the testes, the female duct system has little to no actual contact with the ovaries. An ovulated oocyte is cast into the peritoneal cavity, and some oocytes are lost there. The uterine tubes (fallopian tubes/oviducts) form the initial part of the female duct system. They receive the ovulated oocyte and are the site where fertilization generally occurs. Each uterine tube is about 10cm long and receives an egg and provides a site for fertilization The ampulla, infundibulum, and fimbriae make up the rest of the tube and carry the released oocyte into the peritoneal cavity. Fimbriae direct the oocyte into the ampulla of the oviduct. The structure of the wall of the oviduct also helps oocytes move toward the uterus: -muscular peristalsis -beating cilia Externally, the uterine tubes are covered by visceral peritoneum and is supported by the mesosalpinx. The uterine isthmus is the inferior-posterior part of uterus, on its cervical end — here the uterine muscle (myometrium) is narrower and thinner. It connects superiorly-anteriorly to the complementary parts of the uterus: the body and the fundus. • Anatomy of the Uterus The uterus is located in the pelvis, anterior to the rectum and postero-superior to the bladder. It receives, retains, and nourishes a fertilizes ovum (embryo). In a fertile woman who has never been pregnant, the uterus is about the size and shape of an inverted pear. -internal os: uterus to cervix -external os: cervix to vagina The mucosa of the cervical canal contains cervical glands that secrete a mucus that fills the cervical canal and covers the external os, presumably to block the spread of bacteria from the vagina into the uterus. It also blocks sperm entry except at midcycle, when it becomes less viscous and allows sperm to pass through. - Supports of the Uterus: -mesometrium: laterally (broad ligament) -lateral cervical ligaments: inferiorly, from cervix/upper vagina to lateral walls of pelvis -uterosacral ligaments: to sacrum posteriorly -round ligaments: to anterior body wall The supports (ligaments) allow the uterus a good deal of mobility and its position changes as the rectum and bladder fill and empty. The principal support is by the muscles of the pelvic floor, the urogenital and pelvic diaphragms. - Uterine Wall is composed of three layers: i) Perimetrium: incomplete outermost serous layer (Visceral peritoneum) ii) Myometrium: bulky middle layer, composed of interlacing bundles of smooth muscle, contracts rhythmically during childbirth to expel the baby from the mother’s body iii) Endometrium: mucosal lining of the uterine cavity, simple columnar epithelium and thick lamina proper -stratum functionalis: undergoes cyclic changes in response to blood levels of ovarian hormones and is shed during menstruation -stratum basalis: stem cells form a new functionalism after menstruation ends - Vascular Supply: the vascular supply of the uterus is key to understanding the cyclic changes of the uterine endometrium. The uterine arteries (from internal iliacs) send branches into the uterine wall and break up into several arcuate arteries within the myometrium that send radial arteries into the endometrium, where they give off straight arteries to the status basalts and spiral arteries to the stratum functionalis. • Anatomy of the Vagina The vagina is a thin-walled tube (8-10cm long), with the urethra embedded in the anterior wall. Often called the birth canal, the vagina provides passageway for the entry of sperm, exit of menstrual flow, and the delivery of an infant. The distensible wall of the vagina consists of three coats: -adventitia: outer fibroelastic layer -muscularis: smooth muscle -mucosa: inner, transverse rugae, stratified squamous epithelium -no glands, lubrication is provided by cervical mucous glands -epithelial cells release large amounts of glycogen, which resident bacteria metabolic anaerobically to lactic acid, acidic pH deters infection (hostile to sperm) -hymen: incomplete vascular partition of mucosa near vaginal orifice in virgins • Anatomy of the External Genitalia -vulva: mons pubis, labia, clitoris, and structures sccociated with the vestibule -mons pubis: fatty rounded area overlying pubic symphysis, covered with hair -labia majora: elongated, hair-covered fatty skin folds (homologue of scrotum) -labia minora: thin, hair-free skin folds enclosed by labia majora -vestibule: recess between labia minora, contains external opening of urethra and vaginal opening, greater vestibular glands -clitoris: erectile tissue (homologous to penis), hooded by skin fold, richly innervated, corpora cavernosa but no corpus spongiosum • Regulation of Female Reproductive Function The ovaries have two key functions, to produce oocytes and to produce reproductive hormones. Reproductive hormones include estradoil (from androstenedione to testosterone) and progesterone (from cholesterol). There are three types of steroid hormones produced in the ovarian follicle. These include: a) Progestins (ie. progesterone, all have 21 carbons) -produced by all major ovarian cell types (follicular granulosa cells, theca cells, corpus luteum) -most important as a product of the corpus luteum, during the luteal phase of the menstrual cycle and for the maintenance of pregnancy b) Androgens (ie. testosterone, all have 19 carbons) -most important as a precursor for synthesis of estradiol in developing follicle -synthesized by follicular theca cells and by the corpus luteum -too much testosterone is associated with follicular atresia c) Estrogens (ie. estradiol, all have 18 carbons) -synthesized by follicular granulosa cells and the corpus luteum -essential for stimulation of follicular development, onset of puberty, etc. The hypothalamic-pituitary axis controls the regulation of the female reproductive system. Its anterior pituitary hormones include: -FSH: stimulates ovarian follicles to grow and produce estradiol -LH: stimulates testosterone production by theca cells, stimulates ovulation and the secretion of steroid hormones by the corpus luteum -hypothalamus: the secretion of both FSH and LH is stimulated by GnRH • Ovarian Follicular Development The monthly series of events associated with the maturation of an egg is called the ovarian cycle. The goal of each menstrual cycle is essentially to get pregnant. 1) Primordial follicle: starting point of the ovarian cycle, oocyte is surrounded by a single layer of flattened follicular cells (will become granulosa cells) -oocyte (primary oocyte) arrested at prophase of meiosis I -by 6 months postpartum, the ovary has a full complement of primordial follicles -there are around 2 million primordial follicle at birth, with a gradual loss (degeneration) throughout the woman’s lifetime, 400,000 remain by puberty Initiation of development of primordial follicles does not require gonadotropic stimulation, some follicles can and do begin developing at any time. Oogonia mature to primary oocytes by birth. - Prior to release from the ovary oocytes (eggs, ova) are arrested at an early stage of the first meiotic division as a primary oocyte (primordial follicle). Following puberty, during each menstrual cycle, pituitary gonadotrophin stimulates completion of meiosis 1 the day before ovulation. - The normal, common fate of most primary oocytes is atresia. Atresia is the degeneration of ovarian follicles that do not ovulate during the menstrual cycle. 2) A primordial follicle becomes a primary follicle. -gonadotropin-independent -the oocyte increases in size and acquires a zone pellucida, granulosa cells start to divide and form several layers outside the oocyte, the outside basement membrane ovarian interstitial cells closest to the growing follicle differentiate to form theca cells -now called a primary follicle, the continued maturation of this follicle requires FSH 3) A secondary follicle becomes an antral follicle. -6 to 7 layers of granulosa cells are present, the fluid (clear liquid) between the granulosa cells coalesces to form a large fluid-filled cavity called the antrum -presence of an antrum distinguishes vesticular (antral) follicles from all prior follicles -the basement membrane divides the follicle into 2 compartments: i) inner granulosa cell compartment: nonvascularized, FSH responsive -granulosa cell proliferation (E), granulosa cell E production, more FSH receptors ii) outer theca cell compartment: vascularized, LH-responsive -T production for use by granulosa cells Theca Cell Granulosa Cell Timing is everything. If development coincides with rising FSH levels at the beginning of the cycle, development will be supported (otherwise atresia). For one follicle to become dominant, it must convert from a potentially androgenic environment to an estrogenic environment 4) Emerging dominant follicle becomes the preovulatory follicle. -estrogen levels continue to rise, FSH switches to inducing receptors for LH (LH stimulates further estrogen and progesterone production) -the stage is now set for an LH surge to trigger ovulation Ovulation and its Regulation - Ovulation occurs when the ovary wall ruptures and expels the secondary oocyte into the peritoneal cavity. - Hormonal interactions during the ovarian cycle: -GnRH stimulates FSH and LH secretion -FSH and LH stimulate follicles to grow, mature, and secrete sex hormones -Negative feedback inhibits gonadotropin release -Positive feedback stimulates gonadotropin release -LH surge triggers ovulation and the formation of the corpus luteum -Negative feedback inhibits LH and FSH release LH stimulates: resumption of meiosis extrusion of PB#1, progesterone production by granulosa cells, increase in astral fluid volume, and a release of hydrolytic enzymes. A minor FSH surge ensures a sufficient amount of LH receptors for the luteal phase and stimulates the synthesis of hyaluronic acid (important in cumulus expansion). - Cumulus cells are a cluster of cells that surround the oocyte both in the ovarian follicle and after ovulation. The cumulus-oocyte complex (COC) is ovulated during the ovulatory phase of the menstrual cycle and is just what it seems: an oocyte surrounded by specialized granulosa cells, called cumulus cells. The cumulus cells surrounding the oocyte ensure healthy oocyte and embryo development. • Corpus Luteum The corpus luteum are yellow body capillaries that bring cholesterol to follicles. It consists of luteinized granulosa, theca cells, and capillaries. Unless a pregnancy intervenes, the lifespan of the corpus luteum is less than 14 days. Human chorionic gonadotropin (hGC) signals the corpus luteum to continue progesterone secretion, thereby maintaining the thick lining (endometrium) of the uterus and providing an area rich in blood vessels in which the zygote(s) can develop • Cyclical Regulation of the Uterine Endometrium The uterine (menstrual) cycle is a series of cyclic changes that the uterine endometrium goes through each month as is responds to the waxing and waning of ovarian hormones in the blood. a) Menstrual Phase: the functional layer of the endometrium is shed b) Proliferative Phase: the functional layer of the endometrium is rebuilt -endometrium rebuilds itself under the influence of rising estrogen levels -development of spiral arteries and uterine glands -rising estrogen levels cause cervical mucus to thin and form channels, which forms channels that facilitate sperm passage into the uterus c) Secretory Phase: begins immediately after ovulation, enrichment of the blood supple and glandular secretion of nutrients prepare the endometrium to receive an embryo -endometrium prepares for an embryo to implant -thickening of whole layer due to cell growth and fluid retention -called the secretory phase because it changes the functional layer to a secretory mucosa, as well as all the nutrients secreted -cervical mucus becomes thick again, forming the cervical plug, which helps to block the entry of sperm and pathogens As LH levels decline, the corpus luteum begins to degenerate (day 24). In absence of progesterone secretion, the uterine endometrium is shed and the cycle begins again. If the oocyte is fertilized, hCG is produces in increasing amounts beginning day 9-13 after ovulation, hCG rescues the corpus luteum until placental progesterone can maintain pregnancy. • Hormonal Regulation of Puberty The initial hormonal events are the same in males and females. In females, FSH stimulates estrogen (estradiol) secretion by granulosa cells (LH stimulation provides the testosterone precursor from theca cells). Estradiol is responsible for: -growth and maturation of breasts and reproductive organs -fat redistribution -bone maturation (from growth to closure of epiphyseal plates) In puberty, cycles of proliferation and regression occur until sufficient growth that withdrawals steroid support, which results in first menstruation (menarche). The first ovulatory cycle often may not occur until a few months later. A critical ratio of fat to lean must exist before menarche, acting as a protective mechanism to women not yet able to physically support a pregnancy. • Menopause Menopause is the cessation of menses (menstruation) for at least 12 months. In America, this typically occurs at an average age of 50 years, with the primary cause being the depletion of ovarian follicles. Women can live 1/3rd of their lives after ovaries have ceased functioning. - Perimenopause: extends from early 40s onwards (transitional yea
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