Female Reproductive System (Part I) PDF

XY2141. HISTOLOGY. FEMALE REPRODUCTIVE SYSTEM PART I Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected] 1  LEARNING OUTCOMES HIST.2...

XY2141. HISTOLOGY. FEMALE REPRODUCTIVE SYSTEM PART I Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected] 1  LEARNING OUTCOMES HIST.23 - Reproductive Female HIST.23.01- List the main features of the cortex and medulla of the ovary HIST.23.02 - Describe the origin and development of oocytes before birth HIST.23.03 - List the steps involved in the maturation of an ovarian follicle during the follicular phase HIST.23.04 - Prepare a labeled diagram of a Graafian follicle HIST.23.05 - Describe the process of ovulation and fertilization HIST.23.06 - Give the derivation, structure and function of the corpus luteum HIST.23.07 - Distinguish between a corpus luteum of menstruation and a corpus luteum of pregnancy HIST.23.08 - Distinguish between an atretic follicle and a corpus albicans HIST.23.09 - Give the main features of the oviduct and explain how it nourishes & transports the ovum 2  FEMALE REPRODUCTIVE SYSTEM (FRS) Internal organs – located in the pelvis (ovaries, uterine tubes, uterus, and vagina) External genitalia – located in perineum (mons pubis, labia majora and minora, clitoris, vestibule and opening of the vagina, and external urethral orifis). Accessory sex glands – mammary gland, Skene’s (lesser vestibular) glands, Bartholin's (greater vestibular) glands, and pregnancy-related structures, such as placenta, umbilical cord. 3  FUNCTIONS OF FRS Ensure maturation of female gametes (oocytes), their release and transport. Facilitate sexual intercourse, they create a microenvironment suitable for fertilisation of an oocyte and the subsequent development of an embryo ultimately into a fetus; Undergoing labour giving childbirth. Produce sex hormones – this process is mainly controlled by substances secreted by the hypothalamic-pituitary axis. These hormones also trigger regular cycles where female genital organs are subject to morphological and functional changes between the onset of menarche and the onset of menopause. 4  OVARIUM – OVARY Paired female gonads Almond-shaped, pinkish-white paired organs. Each ovary lies in broad ligament Functions: Reproductive - production of gametes - ova; Endocrine - production and secretion of female sex hormones: estrogens and progesterone. 5  FEMALE SEX HORMONES Estrogens promote the growth and maturation of female sex organs and sex characteristics that develop at puberty. Act on mammary glands to promote breast development by stimulating ductal and stromal growth and accumulation of adipose tissue. Progestogen prepares the internal sex organs for pregnancy by promoting secretory changes in the endometrium. Prepares the mammary gland for lactation by promoting lobular proliferation. 6  OVARIAN STRUCTURE Surface of the ovary is covered by a single layer of a simple cuboidal epithelium (germinal epithelium). CT forms a thin capsule called tunica albuginea. Ovary is divided into: o outer cortex (CT stroma in which the ovarian follicles are embedded.) o inner medulla (loose CT, which contains blood vessels and nerves). 7  EARLY OVARIAN DEVELOPMENT 1st month of embryonic life primordial germ cells migrates from the yolk sac to the gonadal primordia. In the gonads these cells differentiate as oogonia. Oogonia divide by mitosis for the next few months, and some differentiate into primary oocytes. 3rd month, oogonia begin to enter the prophase of the first meiotic division but without progressing to later stages. By 5th month of development there are about 7 million primary oocytes, but most will degenerate by the birth time. Those that remain will be surrounded by a single layer of squamous epithelial cells (follicle cells) called a primordial follicle. Degeneration of primary oocytes continues. At birth = 1million primordial follicles At puberty 300,000 remain. 8  OVARIAN FOLLICLES Ovarian cortex shows various stages of developing follicles: primordial follicle, primary follicle, secondary follicle, Graafian follicle + after ovulation corpus luteum, corpus albicans, and atretic follicles. 9  OVARIAN FOLLICLES Follicles provide the microenvironment for the developing oocyte. Follicles of various sizes, each containing a single oocyte. The size of a follicle indicates the developmental state of the oocyte. Normally, only one oocyte reaches full maturity. Maturation and release of more than one egg at ovulation may lead to multiple zygotes. During the reproductive life span, a woman produces only about 400 mature ova. 10  FOLLICLE DEVELOPMENT follicle = one oocyte + surrounding follicular cells. Types of ovarian follicles: primordial follicles; growing follicles: primary, secondary; mature, dominant follicle or Graafian follicle. 11  PRIMORDIAL FOLLICLES First appear in the ovaries during the 3rd month of intrauterine life (IUL). By the 7th month of IUL, all the oogonia are transformed into primary oocytes. Early growth of the primordial follicles is independent of gonadotropin stimulation. Oocyte remains in this stage till puberty, and further development takes place after puberty under the influence of gonadotropins (FSH and LH) secreted by the anterior pituitary. 12 HORMONAL REGULATION OF FRS 13  PRIMORDIAL FOLLICLES Located in the peripheral part of cortex. Consists of the oocyte in prophase of the first meiotic division surrounding by a single layer of squamous follicle cells. Outer surface of the follicle cells is bounded by a basal lamina. Cytoplasm of the oocyte, referred to as ooplasm, contains a Balbiani body and annulate lamellae. 14  PRIMORDIAL FOLLICLES Balbiani body is a localised accumulation of Golgi membranes and vesicles, ER, centrioles, numerous mitochondria, and lysosomes. Annulate lamellae resemble a stack of nuclear envelope profiles. Each layer of the stack includes pore structures that are morphologically identical to nuclear pores. 15  EARLY PRIMARY FOLLICLE Consists of the oocyte surrounding by a single layer of cuboidal or columnar follicular cells (early, or unilaminar primary) follicle. Homogeneous, acidophilic refractive layer called zona pellucida (glycoproteins between the oocyte and granulosa cells) becomes visible. Zona pellucida is secreted by growing oocyte and follicular cells. Zona pellucida in humans is composed of ZP glycoproteins termed ZP-1, ZP-2, and ZP-3. ZP-3 is the spermatozoa-binding receptor and inducer of the acrosome reaction. 16  LATE PRIMARY FOLLICLE Continued proliferation of granulosa cells will result in the formation of the stratified epithelium surrounding the oocyte (multilaminar primary follicle). Follicular cells multiply to form membrane granulosa cells (stratum granulosum) Granulosa – contains granulosa cells (renamed follicular cells) During follicular growth, gap junctions develop between granulosa cells. Movement of nutrients and informational macromolecules from the blood into the follicular fluid is essential for normal development of the follicle. Surrounding stromal CT cells surrounding the follicle form 17 concentric sheaths - theca folliculi (theca = cover).  SECONDARY FOLLICLES When the stratum granulosum reaches a thickness of 6 to 12 cell layers, fluid-filled cavities appear among the granulosa cells. As the hyaluronan-rich follicular fluid (liquor folliculi) continues to accumulate among the granulosa cells, the cavities begin to coalesce, eventually forming a single cavity called the antrum. Follicle is now identified as a secondary follicle or antral follicle Follicular fluid contains high concentrations of steroids (progesterone, androstenedione, and estrogens) with binding proteins. Oocyte is now located eccentrically and is surrounded by 18 granulosa cells.  THECA FOLLICLE Theca follicle gets differentiated further into 2 layers: inner theca interna and outer theca externa. Distinct basement membrane separates the granulosa cells from the theca interna. Theca interna: highly vascularised layer of cuboidal secretory cells, possess a large number of luteinizing hormone (LH) receptors. In response to LH stimulation, they synthesize and secrete the androgens that are the precursors of estrogens. Theca externa: contains CT cells, smooth muscle cells and 19 bundles of collagen fibers.  ESTROGENS In humans, LH (adenohypophysis) stimulates the cells of the theca interna to secrete androgens, which serve as estrogen precursors. Some androgens are transported to the granulosa cells. In response to FSH (adenohypophysis), the granulosa cells catalyze the conversion of androgens to estrogens (enzyme aromatase), which in turn stimulate the granulosa cells to proliferate and thereby increase the size of the follicle. 20  MATURE (TERTIARY, PREOVULATORY, GRAAFIAN) FOLLICLE During each menstrual cycle, one follicle grows more than others and becomes mature (dominant). While other developing follicles undergo atrophy (atresia). Cavities form a single large antrum. Oocyte is displaced to one side of the follicle. A few layers of follicular cells that immediately surround the oocyte are called corona radiata. Some of the follicular cells concentrate at one point, projecting into the antrum; these cells 21 together are called cumulus oophorus. SUMMARY 22 SUMMARY 23  OVULATION Ovulation is a hormone-mediated (LH) process of liberation of the secondary oocyte by the rupture of Graafian follicle into the peritoneal cavity. Ovulation takes place in the middle of the menstrual cycle, on the 14th day of a 28-day cycle. Secondary oocyte (not ovum yet) and its corona radiata cells leave the ruptured follicle at the ovarian surface to enter the fimbriated end of the oviduct. 24 OVULATION 25  OVULATION In the hours before ovulation the large mature follicle bulging against the tunica albuginea develops a whitish or translucent ischemic area, the stigma, in which the compaction of the tissue has blocked blood flow. 26  OVULATION If sexual intercourse takes place at about this time (ovulation), the spermatozoa deposited in the vagina swim into the uterus and into the uterine tube. One of these spermatozoa may fertilize the secondary oocyte. ! Cannot be used as the only method of contraception – it’s very unreliable 27 OVULATION TEST 28  CORPUS LUTEUM (YELLOW BODY) After ovulation, the follicular wall, composed of the granulosa and theca cells, is transformed into the temporary endocrine gland called corpus luteum (luteal gland). Corpus luteum secretes mainly a hormone progesterone. From the Latin luteus, meaning “saffron- yellow” 29  DEVELOPMENT OF THE CORPUS LUTEUM Includes 4 stages: I. Proliferation and vascularisation - cells of the granulosa and theca interna proliferate; blood vessels from theca interna rapidly grow into the granulosa layer. II. Glandular metamorphosis – cells of the granulosa and theca interna (luteal cells) increase in size and become filled with yellow pigment lutein, and demonstrate features associated with steroid-secreting cells (abundant sER and mitochondria). 30  DEVELOPMENT OF THE CORPUS LUTEUM III. ‘Flowering’ - cells of corpus luteum secrete female sex hormones: 1) granulosa lutein cells, derived from the granulosa cells, secrete progesterone and inhibin; 2) theca lutein cells, derived from the cells of theca interna layer, secrete androgens and estrogens (small amount) and progesterone. Progesterone stimulate the growth and 31 secretory activity of the endometrium, to prepare it to the implantation of the zygote.  EFFECTS OF PROGESTERONE Inhibits the release of LHRH from the hypothalamus and LH from the basophils of the anterior pituitary; Causes the development of the uterine endometrium Regulates the viscosity of the mucus produced by the glands of the uterine cervix; Causes the development of female sexual characteristics, including breasts; Suppresses T cell–mediated rejection of the fetus. 32  DEVELOPMENT OF THE CORPUS LUTEUM IV. Degeneration and involution of the corpus luteum after pregnancy or menstruation. White scar, the corpus albicans, is formed. It slowly disappears over a period of several months. 33  TYPES OF THE CORPUS LUTEUM 1) If the oocyte is not fertilised: * corpus luteum stops secreting progesterone and remains only for 14 days of 28-days cycle; in this case it is called the menstrual corpus luteum. 2) If the oocyte is fertilised and implantation occurs: * trophoblast cells of the blastocyst secrete the hormone human chorionic gonadotrophin (HCG). * HCG signals the corpus luteum to continue progesterone secretion, thereby maintaining the endometrium of the uterus and providing an area in which the zygote(s) can develop. * In this case the corpus luteum is called the corpus luteum graviditatis (corpus luteum of pregnancy). 34  CORPUS LUTEUM GRAVIDITATIS (PREGNANCY) In early pregnancy, the corpus luteum measures 2 to 3 cm, thus filling most of the ovary. Its function begins to decline gradually after 8 weeks of pregnancy, although it persists throughout pregnancy. Although the corpus luteum remains active, the placenta produces sufficient amounts of estrogens and progestogens from maternal and fetal precursors to take over the function of the corpus luteum after 6 weeks of pregnancy. 35 36  HOW DO WE USE IT? hCG can be detected in the serum as early as 6 days after conception and in the urine as early as 10 to 14 days of pregnancy. Detection of hCG in the urine by specific antibodies forms the basis of most over-the-counter pregnancy tests. The rapid increase of the level of hCG in early pregnancy is responsible for “morning sickness,” a condition characterised by nausea and vomiting. These symptoms usually occur in the early hours of the morning and are often among the first signs of pregnancy. 37  FOLLICULAR ATRESIA Follicular atresia - programmed destruction of follicles in apoptosis Most of the ovarian follicles degenerate and undergo follicular atresia. Events in follicular atresia: 1. Initiation of apoptosis by granulosa cells 2. Autolysis of granulosa cells by proteolytic enzymes 3. Hypertrophy of theca interna cells 4. Replacement of follicular cells by CT Macrophages remove degenerating follicular cells, oocyte, and ZP by phagocytosis. Characteristic of degenerating follicle: basement membrane separating theca interna and granulosa cells become thick to form wavy hyaline glassy membrane. FOLLICULAR ATRESIA 39  HILUS CELLS (HILAR CELLS) Hilus cells (hilar cells) – arranged in clusters within the hilum area Shape: ovoid to polygonal (polyhedral) Nucleus: 1 spherical (eccentrically located) Cytoplasm staining: eosinophilic (high intensity) Characteristics: contain Reinke's crystalloids (resembling interstitial endocrine cells of Leydig in the testes) – enzymatically produce androgens from estrogens – originate from fibroblasts Hyperplasia or tumors associated with these cell usually lead to masculinization. 40  CLINICAL CORRELATION Ovarian cysts - fluid-filled sacs (>2 cm in diameter) that typically arise from epithelial components of the ovary, mostly Graafian follicles - are usually benign and asymptomatic. They commonly occur in reproductive-age women; diagnosis is by palpation, ultrasonography, or pelvic computed tomography. Two types of functional cysts (follicular and less common luteal) usually regress spontaneously with time. If they produce unwanted complications, treatment options are minimally invasive laparoscopic or more radical laparotomic surgical excision. Polycystic ovarian syndrome - common hormonal disorder characterized by infrequent or prolonged menstrual periods; abnormally enlarged ovaries contain multiple subcortical follicular cysts with hyperplastic theca interna. 41  OVARIAN CYCLE During each menstrual cycle, the ovary undergoes cyclic changes that involve two phases: follicular phase; luteal phase. Ovulation occurs between two phases. The beginning of the follicular phase in the ovary coincides with the onset of menstruation in the uterus. 42  RELATIONSHIP OF EVENTS THAT OCCUR IN OVARIAN CYCLE 1. Follicular phase: under the influence of pituitary FSH a small number of primary follicles (10 to 20) start to grow and develop. Growing follicles produce estrogen Raising level of estrogen in blood – negative feedback on the pituitary gland to reduce the secretion of FSH ! Crucial event: surge of LH Ovulation is induced by a surge of the LH level and occurs approximately 10 to 12 hours after the peak of the LH LH starts the formation of corpus luteum at the place of collapsed follicle 43  RELATIONSHIP OF EVENTS THAT OCCUR IN OVARIAN CYCLE 2) Luteal phase begins after ovulation, as the granulosa and thecal cells of the ruptured follicle undergo transformation to form the corpus luteum. Some estrogens and large amounts of progesterone are secreted by the corpus luteum. LH stimulates the secretion of progesterone by the corpus luteum. Release of FSH and GnRH is inhibited by inhibin. 44 O v a r i a n c y c l e 45  FALLOPIAN TUBE (OVIDUCT) Paired muscular tubes about 12 cm long Сonnect the peritoneal cavity with the cavity of uterus. Receive and transport ovum to the uterus and provide the necessary environment for fertilization and initial development of the zygote. Oviduct (fallopian tube) is divided into four regions: infundibulum, ampulla, isthmus, 46 intramural portion  FALLOPIAN TUBE (OVIDUCT) Mucosa, Muscularis, Serosa I. Mucosa has longitudinal folds and consists of: 1) epithelium is simple columnar and contains two types of cells: - ciliated cells, wave of the cilia of these cells is directed toward the uterus; - non-ciliated, secretory, peg cells which produce the fluid that provides nutrition for the ovum. 2) lamina propria is composed of loose CT; II. Muscularis consists of 2 sublayers of smooth muscle tissue (outer longitudinal and inner-circular); III. Serosa is covered by mesothelium. 47 FALLOPIAN TUBE (OVIDUCT) 48 FALLOPIAN TUBE (OVIDUCT) 49  EPITHELIUM Simple columnar epithelium is under hormonal control: 1. Ciliated cells, which enlarge and produce cilia (ciliogenesis) as folliculogenesis and estrogen production is in progress. Estrogens increase the rate of the ciliary beat. During luteolysis (regression of the corpus luteum), ciliated cells lose their cilia (deciliation). 2. Nonciliated secretory cells (peg cells), whose secretory activity is also stimulated by estrogens; provide nutrients to the egg during its migration. 50  FALLOPIAN TUBE (OVIDUCT) 51