FEMALE REPRODUCTIVE SYSTEM MIDTERMS, 2ND SEM SY 2024-2025 • Early Development : Consist of : 1. ovaries 2. uterine / fallopian tubes 3. uterus 4. vagina 5. external genitalia Functions : 1. Produces female gametes (oocytes) 2. Provides the environment for fertilization 3. Holds the embryo during its complete development through the fetal stage until birth Menarche stage where first menstrual cycle occurs Menopause represents a variably timed period during which the cyclic changes become irregular and eventually disappears Post-menopausal period PRIMORDIAL FOLLICLES → Develop at the superficial ovarian cortex during fetal life with input from gonadotropin → Consist primarily of oocytes enveloped by a single layer of squamous or flattened follicular cells. → Nucleus contains chromosomes in the first meiotic prophase. → Basal lamina surrounds the follicular cells marks a clear boundary between follicle and the vascularized stroma ● Act as a blood-follicle barrier PRIMARY FOLLICLES 1. Unilaminar Primary Follicle → Consist of a single layer of cuboidal follicular cells surrounding the oocyte → Undergoes growth and maturation 2. Multilaminar Primary Follicle → Presence of one or more cuboidal follicular (“granulosa”) cells arranged in s single layer surrounding the oocyte → Enters the first phase of meiotic division and arrests there Reproductive organs slowly involute FOLLICULAR GROWTH AND DEVELOPMENT ➤ Puberty : release of Follicle-Stimulating Hormone (FSH) from the pituitary gland → Primordial follicles each month begin to grow and 1. OVARIES → Almond-shaped bodies → Covered by simple cuboidal epithelium (surface or germinal epithelium) → Continuous w/ mesothelium and overlying capsule of dense connective tissue (tunica albuginea) → Cortex: region of highly cellular connective tissue stroma containing many ovarian follicles → Medulla: loose connective tissue and blood vessels → Produces both oocytes and sex hormones (estrogen and progesterone) develop. ● Enlargement of oocyte ● Mitoses ● Thickening of follicular cells ● Proliferation and differentiation of stromal fibroblasts around each follicle → Dominant follicle is destined to ovulate each month. → Follicular cells divide and enlarge (from simple squamous epithelium to simple cuboidal epithelium) → Proliferation of cuboidal follicular cells → stratified epithelium (“granulosa cells) → The first layer of granulosa cells forms the zona pellucida ● Contains sperm-binding receptors that attach specific proteins on capacitated sperm ● Begins acrosomal activation → allows sperm to progress through this extracellular molecule → Stromal cells differentiate to form vascularized follicular theca (Gr theca: outer covering) that develops into two layers: 1. Theca interna → well-vascularized endocrine tissue that responds to Luteinizing Hormone to secrete androstenedione → 𝐴𝑛𝑑𝑟𝑜𝑠𝑡𝑒𝑛𝑒𝑑𝑖𝑜𝑛𝑒 𝑎𝑟𝑜𝑚𝑎𝑡𝑎𝑠𝑒 𝑒𝑛𝑧𝑦𝑚𝑒 / 𝐹𝑆𝐻 → 𝐸𝑠𝑡𝑟𝑎𝑑𝑖𝑜𝑙 2. Theca externa → more fibrous layer containing smooth muscles that merges gradually with the surrounding stroma SECONDARY OR ANTRAL FOLLICLE → Growing primary follicles move deeper into the ovarian cortex → Granulosa cells secretes follicular fluid that accumulates taking up space and gradually coalesce (contains high levels of steroids: progesterone, androstenedione and estrogens) → Cavity: “Antrum” → As it develops, the oocyte and granulosa cells immediately around it form a small hillock, cumulus oophorus, that protrudes into the antrum → Granulosa cells adhering to the oocyte through the zona pellucida comprise the corona radiata GRAAFIAN FOLLICLE → INHIBIN Produced by granulosa and luteal cells of the ovary → Exerts a negative feedback on anterior pituitary gland and hypothalamus to stop the production of FSH and LH → Stimulated by high amounts of estrogen PRE-OVULATION → Dominant follicle releases higher levels of estrogen → Stimulate more rapid pulsatile secretions of GnRH from the hypothalamus → Pituitary gland releases a surge of Luteinizing Hormone that rapidly triggers a sequence of events in the follicle: → Meiosis I is completed by the primary oocyte yielding a secondary oocyte and the first shortlived polar body → Each month, only one antral follicle becomes a mature or Graafian follicle with a single large antrum → Granulosa layer becomes thinner and no longer multiply in proportion to the growth of the antrum. → (+) Thick theca layers FOLLICULAR ATRESIA → Degenerative process in which follicular cells and oocytes undergo apoptosis and removal by phagocytic cells → Follicles at any stage of development may undergo atresia Involves the following steps 1. Detachment of apoptotic granulosa cells • Autolysis of oocyte 2. Collapse of the zona pellucida 3. Macrophage phagocytosis and removal of apoptotic bodies and other debris → Granulosa cells becomes specialized as “granulosa lutein cells” produces progesterone → Theca interna becomes “theca lutein cells” continue to produce estrogen If pregnancy did not occur : • LH level declines causing the corpus luteum to cease hormone production and undergo apoptosis, forming corpus albicans • Reduction in progesterone leads to: ● Menstruation ● Greatly renewed pituitary secretion of FSH -> stimulate growth of another group of follicles If pregnancy occurs : OVULATION → Hormone-stimulated process by which the oocyte undergoes release from the ovary → Normally occurs midway through the menstrual cycle • Corpus luteum continues to produce progesterone • Cells surrounding the implanted fertilized embryo in the uterus will begin secreting the human chorionic gonadotropin (hCG) ● hCG functions similarly with LH ● Promote and increase progesterone secretion for the sustained support of the uterine mucosa • Corpus luteum -> Corpus luteum of pregnancy in increases in size then degenerates as the placenta enlarges and produces its own progesterone 2. FALLOPIAN TUBES → “Uterine tubes”, “Oviduct” → If fertilization does not occur within 24 hours, the secondary oocyte begins to degenerate → Cells of the now empty follicle remaining in the ovary redifferentiate under the influence of LH and develop into the corpus luteum CORPUS LUTEUM → Retains in the ovarian cortex after expulsion of the oocyte → Granulosa and thecal layers immediately collapse and fold with blood from disrupted capillaries → Opens into the peritoneal cavity near the paired ovaries Regions : Infundibulum funnel-shaped segment with its fingerlike extensions called fimbriae Ampulla longest and expanded region, where fertilization normally occurs Isthmus a narrow portion adjoining the uterus Uterine / Intramural part passes through the wall of the uterus and opens into the interior of the organ 3. UTERUS 4. MENSTRUAL CYCLE (VAGINA) → Controlled by estrogen and progesterone → From puberty until menopause, pituitary gonadotropins produce cyclic changes in ovarian hormone levels, causing cyclic endometrial modifications during the menstrual cycle → Day 1 : menstrual bleeding begins → A medial, pear-shape organ with thick muscular walls. Parts : Body largest part Fundus curved, superior area between the fallopian tubes Isthmus narrow part of the uterus Cervix lower cylindrical structure at the end of the uterus Layers of Uterine Wall : CERVIX Perimetrium outer connective tissue layer Myometrium middle layer of highly vascularized smooth muscles • Endometrium Endometrium lined by epithelium simple uterus columnar • During pregnancy : → Myometrium increases in size by increasing the number of smooth muscle cells (hyperplasia), increasing the size of muscle cells (hypertrophy) and increases collagen production by the muscle cells to strengthen the uterine wall ENDOMETRIUM • Two concentric zones : 1. → Lower cylindrical part of the Basal layer → adjacent to the myometrium and has a more highly cellular lamina propria and contains the deep basal ends of the uterine glands 2. Functional layer → sponger lamina propria with rich ground substance and includes most of the length of the glands → Responds with estrogen and progesterone → Sheds off during menstruation ➤ Endocervical mucosa → simple columnar epithelium ith many large, branched, mucus-secreting cervical glands ● Lacks spiral arteries of the uterine endometrium ● Does not thicken in response to the cyclic changes of estrogen and progesterone ➤ Exocervical mucosa → nonkeratinized stratified squamous epithelium that is continuous with that of the vagina ● Transformation zone → VAGINA Lacks glands and is kept moist mainly by the cervical gland secretions • Layers : 1. Mucosa → stratified squamous epithelium → Lamina propria has abundant elastic fibers → Contains large quantities of lymphocytes and neutrophils 2. Muscularis layers : 2 distinct layers of smooth muscle • Inner circular • Outer longitudinal 3. Adventitia → rich on elastic fibers with extensive venous plexus, lymphatics and nerves 5. EXTERNAL GENITALIA / VULVA → Contains numerous Meissner and Pacinian corpuscles → Covered by stratified squamous epithelium. Parts of the External Genitalia : Paired majora labia consist of thick lateral folds of skin homologous to and similar histology to the skin of the scrotum Paired minora labia smaller folds, medial and parallel to the labia majora, contains numerous sebaceous glands and melanocytes Vestibule space in between the 2 labias, encompasses the urethral and vaginal openings ● Vestibule → Greater vestibular glands (Glands of Bartholin) – homologous with the male bulbourethral glands a small erectile structure, homologous to the penis with paired corpora cavernosa BREAST MAMMARY GLANDS Develop embryologically as invaginations of surface ectoderm along two ventral lines (milk lines) from axillae to the groin → Each mammary glands consists of 15-20 lobes of compound tubuloacinar glands → Each lactiferous duct emerge independently at the nipple During Pregnancy and Lactation • Undergo synergistic action of several hormones (estrogen, progesterone, prolactin and placental lactogen) ❖ Proliferation of secretory alveoli of ductal units in preparation for lactation ❖ Late in pregnancy, alveoli and ducts dilate with accumulated colostrum ❖ Abundant plasma cells in the breast stroma secretes IgA antibodies ❖ Lipid droplets form and eventually undergo apocrine secretion ❖ Lactose, the major carbohydrate and energy source in milk is synthesized by Golgi apparatus enzymes Post-lactational Regression • Weaning (stopping of breastfeeding), most alveoli that develop during pregnancy and lactation degenerate • Epithelial cells undergo apoptosis, autophagy, or sloughing with dead cells and debris removed by macrophages • Ductal system return to its general appearance in the inactive state • After menopause, alveoli and ducts are reduced further in size due to loss of fibroblasts, adipocytes, collagen, and elastic fibers in the stroma.