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Histology:2nd stage Dr. Raja Ali --------------------------------------------------------------------------------------The Female Reproductive System Corpus Luteum: The collapsed follicle undergoes reorganization into the corpus luteum after ovulation. At ovulation, the follicular wall, composed of the remaining granulosa and thecal cells, is thrown into deep folds as the follicle collapses and is transformed into the corpus luteum (yellow body), or luteal gland (janqueira). Cells of the granulosa and theca interna layers then differentiate into granulosa luteal and theca luteal cells in the process called luteinization. Two types of luteal cells are identified: • Granulosa lutein cells are large , centrally located cells derived from the granulosa cells. • Theca lutein cells are smaller , more deeply staining, and peripherally located cells derived from the cells of the theca interna layer (janqueira). The corpus luteum highly vascularized structure located in the cortex of the ovary secretes progesterone and estrogens. These hormones stimulate the growth and secretory activity of the lining of the uterus, the endometrium, to prepare it for the implantation of the developing zygote in the event that fertilization occurs. The corpus luteum of menstruation is formed in the absence of fertilization. If fertilization and implantation do not occur, the corpus luteum remains active only for 14 days; in this case it is called the corpus luteum of menstruation. The corpus luteum degenerates and undergoes a slow involution after pregnancy or menstruation. The cells become loaded with lipid, decrease in size, and undergo autolysis. A white scar, the corpus albicans, is formed as intercellular hyaline material accumulates among the degenerating cells of the former corpus luteum (janqueira). The corpus albicans sinks deeper into the ovarian cortex as it slowly disappears over a period of several months. Capacitation and Fertilization During capacitation, the mature spermatozoa acquire the ability to fertilize the oocyte. Following their maturation in the epididymis, spermatozoa must be activated within the female reproductive tract. During this activation process, called capacitation, structural and functional changes take place in the spermatozoon that result in its increased affinity to bind to zona pellucida receptors. Fertilization normally occurs in the ampulla of the uterine tube. Usually, only a few hundred of the millions of spermatozoa in an ejaculate reach the site of fertilization, typically the ampulla of the uterine tube. Spermatozoa must penetrate the corona radiate to gain access to the zona pellucid , only one spermatozoon completes the fertilization process. Capacitation is complete when spermatozoa are able to bind to the zona pellucida receptors. Impregnation of the oocyte allows structures lying inside the spermatozoon to enter the cytoplasm of the oocyte. Blood Supply , Lymphatics and Innervation: Blood supply to the ovaries comes from two different sources: Ovarian and uterine arteries ,these large arteries are called spiral arteries because they branch and become highly coiled as they pass into the ovarian medulla. Veins accompany the arteries and form a plexus called the pampiniform plexus. The lymphatic vessels follow the course of the ovarian arteries as they ascend to paraaortic lymph nodes in the lumbar region. Ovaries are innervated by the autonomic ovarian plexus. Uterine Tubes: The uterine tubes (Fallopian tubes) are paired tubes that extend bilaterally from the uterus toward the ovaries (janqueira). The uterine tubes transport the ovum from the ovary to the uterus and provide the necessary environment for fertilization and initial development of the zygote to the morula stage. Each uterine tube can be divided into four segments by gross inspection: The infundibulum is the funnel-shaped segment of the tube adjacent to the ovary. At the distal end, it opens into the peritoneal cavity. The proximal end communicates with the ampulla. Fimbriae, extend from the mouth of the infundibulum toward the ovary. The ampulla is the the site of fertilization. The isthmus is the narrow, medial segment of the uterine tube adjacent to the uterus. The uterine or intramural part, measuring about 1 cm in length, lies within the uterine wall and opens into the// cavity of the uterus. The wall of the uterine tube is composed of three layers: The serosa or peritoneum is the outermost layer of the uterine tube and is composed of mesothelium and a thin layer of connective tissue. The muscularis, is organized into an inner, relatively thick circular layer and an outer, thinner longitudinal layer. The mucosa, the inner lining of the uterine tube, exhibits thin longitudinal folds that project into the lumen of the uterine tube throughout its length. The folds are most numerous and complex in the ampulla (janqueira) and become smaller in the isthmus. The mucosal lining is simple columnar epithelium composed of two kinds of cells—ciliated and nonciliated (janqueira). Ciliated cells are most numerous in the infundibulum and ampulla. The wave of the cilia is directed toward the uterus. Nonciliated, peg cells are secretory cells that produce the fluid that provides nutritive material for the ovum. Uterus The uterus receives the rapidly developing morula from the uterine tube. All subsequent embryonic and fetal development occurs within the uterus. The uterus is divided into two regions: • The body is the large upper portion of the uterus. The anterior surface is almost flat; the posterior surface is convex. The upper, rounded part of the body that expands above the attachment of the uterine tubes is termed the fundus. • The cervix is the lower, barrel-shaped part of the uterus separated from the body by the isthmus (janqueira). The lumen of the cervix, the cervical canal, has a constricted opening at each end. The internal os communicates with the cavity of the uterus; the external os with the vagina. The uterine wall is composed of three layers (janqueira): • The endometrium is the mucosa of the uterus. • The myometrium is the thick muscular layer. It is continuous with the muscle layer of the uterine tube and vagina. The smooth muscle fibers also extend into the ligaments connected to the uterus. • The perimetrium, the outer serous layer or visceral peritoneal covering of the uterus, is continuous with the pelvic and abdominal peritoneum and consists of a mesothelium and a thin layer of loose connective tissue. Beneath the mesothelium, a layer of elastic tissue is usually prominent. The perimetrium covers the entire posterior surface of the uterus but only part of the anterior surface. The remaining part of the anterior surface consists of connective tissue or adventitia. Both myometrium and endometrium undergo cyclic changes each month to prepare the uterus for implantation of an embryo. These changes constitute the menstrual cycle. If an embryo implants, the cycle stops, and both layers undergo considerable growth and differentiation during pregnancy The myometrium It is composed of three layers of smooth muscle: 1- The middle muscle layer contains numerous large blood vessels (venous plexuses) and lymphatics and is called the stratum vasculare. It is the thickest layer and has interlaced smooth muscle bundles oriented in a circular or spiral pattern. 2&3- The smooth muscle bundles in the inner and outer layers are predominantly oriented parallel to the long axis of the uterus. The endometrium proliferates and then degenerates during a menstrual cycle. During reproductive life, the endometrium consists of two layers or zones that differ in structure and function: • The stratum functionale or functional layer is the thick part of the endometrium, which is sloughed off at menstruation. • The stratum basale or basal layer is retained during menstruation and serves as the source for the regeneration of the stratum functionale. Cyclic Changes During the Menstrual Cycle: Cyclic changes of the endometrium during the menstrual cycle are represented by the proliferative, secretory , and menstrual phases: 1-The proliferative phase : Occurs concurrently with follicular maturation and is influenced by ovarian estrogen secretion. Under the influence of estrogens, the proliferative phase is initiated. Stromal, endothelial, and epithelial cells in the stratum basale proliferate rapidly, and the following changes can be seen: • Epithelial cells in the basal portion of the glands reconstitute the glands and migrate to cover the denuded endometrial surface. • Stromal cells proliferate and secrete collagen and ground substance. • Spiral arteries lengthen as the endometrium is reestablished; these arteries are only slightly coiled and do not extend into the upper third of the endometrium. 2- The secretory phase coincides with the functional activity of the corpus luteum and is primarily influenced by progesterone secretion. 3- The menstrual phase commences as hormone production by the ovary declines with the degeneration of the corpus luteum . If fertilization and implantation occur, a gravid phase replaces the menstrual phase of the cycle. After implantation, the endometrium undergoes decidualization. During pregnancy, the portion of the endometrium that undergoes morphologic changes is called the decidua or decidua graviditas. This layer is shed with the placenta at parturition. The decidua includes all but the deepest layer of the endometrium. Three different regions of the decidua are identified: • The decidua basalis is the portion of the endometrium that underlies the implantation site. • The decidua capsularis is a thin portion of endometrium that lies between the implantation site and the uterine lumen. • The decidua parietalis includes the remaining endometrium of the uterus. Cervix: The endometrium of the cervix differs from the rest of the uterus , contains large, branched glands . It also lacks spiral arteries. The cervical mucosa undergoes little change in thickness during the menstrual cycle and is not sloughed during the period of menstruation. The transformation zone is the site of transition between vaginal stratified squamous epithelium (ecto cervix) and cervical simple columnar epithelium (endo cervix). Placenta: (See Practical Histology) The developing fetus is maintained by the placenta, which develops from fetal and maternal tissues. The placenta consists of a fetal portion, formed by the chorion, and a maternal portion, formed by the decidua basalis. The two parts are involved in physiologic exchange of substances between the maternal and fetal circulations. Proliferation of the cytotrophoblast, growth of chorionic mesoderm, and blood vessel development successively give rise to the following. • Primary chorionic villi . • Secondary chorionic villi . • Tertiary chorionic villi. The placenta is the site of exchange of gases and metabolites between the maternal and fetal circulation. The placenta is a major endocrine organ producing steroid hormones( progesterone and estrogen) and protein hormones (Human chorionic gonadotropin (hCG)). Vagina: The vagina is a fibromuscular tube that joins internal reproductive organs to the external environment. In a virgin, the opening into the vagina may be surrounded by the hymen, folds of mucous membrane extending into the vaginal lumen. The hymen or its remnants are derived from the endodermal membrane that separated the developing vagina from the cavity of the definitive urogenital sinus in the embryo. The vaginal wall consists of the following: • An inner mucosal layer has numerous transverse folds or rugae , and is lined with stratified squamous epithelium . • An intermediate muscular layer is organized into two sometimes indistinct, intermingling smooth muscle layers, an outer longitudinal layer, and an inner circular layer.The outer layer is continuous with the corresponding layer in the uterus. Striated muscle fibers of the bulbospongiosus muscle are present at the vaginal opening . • An outer adventitial layer is organized into an inner dense connective tissue layer adjacent to the muscularis and an outer loose connective tissue layer that blends with the adventitia of the surrounding structures. The Female External Genitalia: The female external genitalia consist of the following parts, which are collectively referred to as the vulva and have a stratified squamous epithelium as follows: • The mons pubis is the rounded prominence over the pubic symphysis formed by subcutaneous adipose tissue. • The labia majora • The labia minora • The clitoris is an erectile structure that is homologous to the penis. • Vestibule. Numerous sensory nerve endings are present in the external genitalia: • Meissner’s corpuscles are particularly abundant in the skin over the mons pubis and labia majora. • Pacinian corpuscles are distributed in the deeper layers of the connective tissue and are found in the labia majora and in association with the erectile tissue. Mammary glands: The mammary glands, or breasts, are a distinguishing feature of mammals. They are structurally dynamic organs, varying with age, menstrual cycle, and reproductive status of the female. In females, mammary glands develop under the influence of sex hormones. In males, testosterone acts on the mesenchymal cells to inhibit further growth of the mammary gland. The mammary glands in women undergo further development under hormonal influence of estrogen and progesterone. The complete morphologic and functional maturation of mammary glands occurs in response to: Estrogens and progesterone initially secreted from the corpus luteum and later from placenta. Prolactin from pituitary gland, and Gonadocorticoids produced by adrenal cortex. The ejection of the milk from the breast is stimulated by oxytocin released from the neurohypophysis. Mammary glands are modified tubuloalveolar apocrine sweat glands. The tubuloalveolar mammary glands, derived from modified sweat glands in the epidermis, lie in the subcutaneous tissue. The inactive adult mammary gland is composed of 15 to 20 irregular lobes separated by fibrous bands of connective tissue. They radiate from the mammary papilla, or nipple, and are further subdivided into numerous lobules known as terminal duct lobular units (TDLUs) {Terminal duct lobular unit (TDLU) of the mammary gland represents a cluster of small secretory alveoli (in lactating gland) or terminal ductules (in inactive gland) surrounded by intralobular stroma. }. Some of the fibrous bands, called suspensory or Cooper’s ligaments, connect with the dermis. Abundant adipose tissue is present in the dense connective tissue of the interlobular spaces. Each gland ends in a lactiferous duct that opens through a constricted orifice into the nipple. Beneath the areola, the pigmented area surrounding the nipple, each duct has a dilated portion, the lactiferous sinus. The lactiferous ducts are lined with stratified squamous keratinized epithelium. The epithelial lining of the duct shows a gradual transition from stratified squamous to two layers of cuboidal cells in the lactiferous sinus and finally to a single layer of columnar or cuboidal cells through the remainder of the duct system. The morphology of the secretory portion of the mammary gland varies with the menstrual cycle. Both merocrine and apocrine secretion are involved in production of milk. • Merocrine secretion: The protein component of the milk is synthesized in the rER , packaged into membrane limited secretory vesicles for transport in the Golgi apparatus, and released from the cell by fusion of the vesicle’s limiting membrane with the plasma membrane. • Apocrine secretion: The fatty or lipid component of the milk arises as lipid droplets free in the cytoplasm.