Embryology and Histology of the Female Reproductive System PDF

EMBRYOLOGY AND HISTOLOGY OF THE FEMALE REPRODUCTIVE SYSTEM SANCHEZ, John Russel VERDEJO, Love DMD-2 Overview Oviduct (FALLOPIAN TUBE)...

EMBRYOLOGY AND HISTOLOGY OF THE FEMALE REPRODUCTIVE SYSTEM SANCHEZ, John Russel VERDEJO, Love DMD-2 Overview Oviduct (FALLOPIAN TUBE) Ovary EMBRYOLOGY Passageway for eggs from the ovaries to the uterus and Gonads provides the site for fertilisation by the sperm Produces eggs (ova) and female sex hormones like Genital Ducts estrogen and progesterone Vagina External Genitalia Descent of Ovaries Uterus HISTOLOGY Where a fertilised egg implants and grows into a Ovary fetus during pregnancy Vagina Uterine Tubes Receives the penis during sexual reproduction, allows the Uterus menstrual blood to exit the body, and lets the baby passes Placenta Cervix through during childbirth Vagina Allows menstrual blood to flow from the uterus and serves as a External Genitalia pathway for sperm to enter the uterus Mammary Glands  Introduction Composed of paired ovaries, oviducts (uterine tubes), uterus, vagina, and external genitalia. Functions include: Production of oocytes (female gametes). Providing an environment for fertilization and embryo/fetal development until birth. Ovaries produce steroidal sex hormones that regulate the reproductive system and influence other body systems. Did You Know? Begins functioning at menarche (first menstrual The vagina is a self-cleaning ecosystem that cycle) with monthly hormonal cycles. contains good bacteria, like lactobacillus, that helps to keep the vagina healthy. Menopause marks the end of these cycles, leading Washing the vagina with soaps and perfumes can disrupt the pH balance and to gradual involution of reproductive organs. introduce harmful bacteria. Mammary glands are included due to their functional connection with reproductive hormones. Development of Female Reproductive System Occurs during embryogenesis and involves precise and sequential steps. Key Processes: Gonadal Differentiation Genital Duct Formation Vaginal Development External Genitalia Development Absence of Male-Specific Factors: No SRY gene, leading to ovarian development. Lack of testosterone allows Wolffian duct regression. Absence of Müllerian Inhibiting Factor (MIF) permits development of female reproductive structures.  Stages in Reproductive System Formation Indifferent Stage: Initially, the reproductive system is sexually undifferentiated. Both gonads and primitive duct systems (mesonephric and paramesonephric ducts) are present. Differentiation Stage: By the 7th week of gestation, differentiation into the female system begins: The gonads develop into ovaries. The paramesonephric ducts become the uterine tubes, uterus, and upper vagina. The mesonephric ducts regress due to the absence of testosterone.  PRIMITIVE REPRODUCTIVE TRACT The reproductive system develops from the mesoderm, which has three types: Paraxial Paraxial Intermediate Intermediate Lateral plate Somatic layer (closer to the ectoderm) Lateral Plate Splanchnic layer (closer to the endoderm) PRIMITIVE REPRODUCTIVE TRACT The reproductive tract is derived from the intermediate mesoderm The intermediate mesoderm will condense and form the urogenital ridge, which will give rise to the: Gonads Ductal system PRIMITIVE REPRODUCTIVE TRACT From the sagittal section of the embryo, the gut tube can be visualized The hindgut area contains the cloaca, which gives rise to two canals separated by the urorectal septum: Urogenital sinus (anterior) Anal canal (posterior) The yolk sac contains the primordial germ cells (PGCs), which will: Migrate through the vitelline duct; and Invade the urogenital ridge The PGCs will give rise to the gametes (sperm and oocytes) Gonads and the Ductal Systems Each fetus has two bipotential gonads and a ductal system which empties into the urogenital sinus The ductal system is made up of the following: Mesonephric / Wolffian Ducts Paramesonephric / Mullerian Ducts Gubernaculum During sexual differentiation, the changes occur in different parts of the gonadal structure In females, changes occur in the cortex Recall: Males have the XY chromosome Females have the XX chromosome Differentiation of the Male and Female Reproductive Tracts Differentiation of the Male and Female Reproductive Tracts Female Reproductive Tracts In females, there is no Y chromosome No SRY Gene No TDF In the absence of TDF, the gonads differentiate into ovaries by default The ovaries are made up of: Follicular cells – produce estrogen Oocytes – arise from PGCs The estrogen from follicular cells will stimulate the formation of the female external genitalia Since there is no testosterone, the mesonephric/Wolffian ducts will regress/not develop Female Reproductive Tracts Since there is no Mullerian- inhibiting hormone, the paramesonephric/Mullerian ducts will grow, giving rise to: Fallopian tube Uterus Upper 2/3 of vagina The gubernaculum guides the descent of the ovaries and ductal system into the pelvis It eventually splits to form: Ovarian ligament – connects the ovary and uterus Round ligament – connects the uterus and labia  Urogenital Sinus The ducts empty into the urogenital sinus The urogenital sinus gives rise to the: Bladder Part of the urethra (prostatic urethra) Vagina The vagina develops through the interaction of the paramesonephric ducts and the urogenital sinus. This process creates the continuous vaginal canal. Upper Two-Thirds of the Vagina The upper portion derives from the most inferior segments of the paramesonephric ducts. Lower One-Third of the Vagina The lower portion originates from the urogenital sinus, a structure derived from the cloaca. The urogenital sinus contributes to the formation of the vaginal plate, a solid column of tissue that later undergoes canalization to form the vaginal lumen. Vagina Clinical Implications and Developmental Abnormalities 1. Müllerian Agenesis (Mayer-Rokitansky- Küster-Hauser Syndrome) Cause: Failure of paramesonephric duct development, leading to the absence of the uterus and upper vagina. Effect: Ovaries and external genitalia remain unaffected, but there is no uterus or vaginal canal. 2. Bicornuate Uterus Cause: Incomplete fusion of the paramesonephric ducts, resulting in a uterus with two cavities. Effect: May cause infertility, pregnancy loss, and menstrual irregularities. Clinical Implications and Developmental Abnormalities 3. Septate Uterus Cause: Incomplete resorption of the central uterine septum, causing a division in the uterine cavity. Effect: Can lead to miscarriage, preterm birth, and fertility issues. 4. Transverse Vaginal Septum Cause: Improper fusion of the Müllerian ducts or failure of vaginal canalization, forming a horizontal membrane across the vaginal canal. Effect: Obstruction of the vaginal canal, causing symptoms like dysmenorrhea, hematocolpos, and sexual dysfunction.  EXTERNAL GENITALIA Stages of External Genitalia Formation 1. Ambisexual Stage (Weeks 3–7): Cloacal Membrane Formation: Cloacal folds form, dividing into anterior urethral folds and posterior anal folds. Genital Tubercle Development: Forms at the superior union of cloacal folds. 2. Sex Differentiation (Weeks 8–12): Genital tubercle minimally elongates into the clitoris; folds remain unfused as labia minora and majora. 3. Final Maturation (Weeks 12–Term): Clitoris, labia majora, and minora increase in size under estrogen, which are derived from androgens.  EXTERNAL GENITALIA CLITORIS(kli·tr·uhs) “Where is it?” Origin: The clitoris was first described in medical texts by the Greek Physician Galen during the 2nd century, though its anatomy was always misunderstood and ignored for centuries afterwards. Location: Between the folds of the labia minora Development: Develops from the genital tubercle by the 8th week of gestation in the absence of significant androgens Role: The sole purpose of the clitoris is sexual pleasure. It has no direct role in the reproduction or urination. Composition: The clitoris has over 9,000 nerve endings, which is more than any other part of the body.  EXTERNAL GENITALIA LABIA MAJORA AND LABIA MINORA (Labia is a Latin word for “Lip”) Origin: Was not “discovered” in a traditional sense, but was always known to humanity Location: The Labia Majora is the outermost folds of skin in the vulva while the Labia Minora is medially to the Labia Majora. Development: The Labia Majora develops from labioscrotal swellings, remain unfused and form the external skin folds. The Labia Minora originates from urogenital folds, remaining unfused to form the external skin folds of the vagina. Role: Lubrication and protection Composition: Contains sebaceous glands, erectile tissue, and nerve endings Descent of Ovaries Around the 8th week of gestation, the ovaries begin their descent toward the pelvis, a process guided by the gubernaculum, a fibrous mesodermal cord that connects the gonads to the developing labioscrotal swellings. This descent continues between weeks 12 and 20, as the ovaries move from the abdominal cavity to the pelvic brim.  Descent of Ovaries Migration of Ovaries The ovaries begin their descent from the posterior abdominal wall (near the developing kidneys). The gubernaculum shortens and pulls the ovaries downward. The ovaries move through the abdominal cavity but remain retroperitoneal. Descent of Ovaries HISTOLOGY OF THE FEMALE REPRODUCTIVE SYSTEM Terminologies: Tunica Albuginea: Fibrous layer of tissue that surrounds the ovaries, testis, and penis. Preantral: (Pre=before, Before Antral stage) Consists of the Primordial, Primary, and Early Secondary stages of the Ovarian Follicular Development. Antral: The Late Secondary stage of the Ovarian Follicular Development, where Antral follicles are present. Zona Pellucida: Protective Layer that separates the oocyte from the zona granulosa. Granulosa cells: Somatic cells in ovaries that produce estrogen and progesterone Theca Interna: Innermost layer of cells in ovarian follicle that produce steroid hormones. Antral Follicles: Contains immature eggs Liquor Folliculi: A viscous yellow fluid that fills the antrum of an ovarian follicle and surrounds the oocyte and helps in sperm motility and permeability. It is also made up of hormones, enzymes, antioxidants, electrolytes, anticoaglutants, and reactive oxygen species (ROS). Terminologies: Motile Cilia: Hair like organelles that protrude form surface of cells and beat rhytmically to move fluids and transport mucus. Ciliated Cells: Hair like projections that move back and forth to remove particles from the body. Non-ciliated cells: Epithelial cells that do not have cilia. Microvilli: Finger like membrane protrusions, which improves the cell’s ability to absorb and secrete substances. Eosinophils: A types of white blood cell that are proinflammatory cells that help fight infections. Ampulla: Widest part of the fallopian tube and the primary site of fertilization. Isthmus: A short, muscular, and rounded section of the fallopian tube that connects the ampulla to the uterus. Terminologies: Tunica Mucosa: Mucous membrane that lines the uterus. Tunica Muscularis: Muscular layer of the uterus that makes up the majority of its substance. Tunica Serosa: The outermost layer of the uterus, composed of mesothelial cells and a thin layer of connective tissue. Mesothelium: Single layer of cells that protects the uterus from physical and biochemical damage. Stratum Vasculare: Plays a key role in uterine contractions and labor. Chorion: Outermost fetal membrane around the embryo. Chorion frondosum: A fingerlike projection that allows the embryo to absorb nutrients and gases from the mother’s blood. Chorion Villi: A fingerlike projection that grows from the chorion. Terminologies: Amnion: A thin membrane that surrounds the embryo and fetus, contains amniotic fluid. Decidua Capsularis: Envelops the embryo as it grows in the uterine cavity. Parietal Decidua: A mucous membrane in the pregnant uterus. Bartholin’s Glands: Pea-sized glands that secrete mucus for lubrication. Skene’s Glands: Two small ducts on either side of the urethra that contributes to lubrication and antibacterial protection. Hyperplasia: An increase in the number of cells in a tissue or organ. Ovaries Ovoid structure divided into outer cortex and inner medulla. Cortex ( outer portion) Broad peripheral zone containing follicles in various stages of development embedded in loose connective tissue stroma and covered by Germinal epithelium which is Simple cuboidal/ columnar (young) and simple cuboidal/ squamous (adult). Stroma: A supporting tissue and covered by Tunica albuginea just beneath the germinal epithelium. Medulla (Inner portion) Contains nerves, blood vessels, lymphatics, loose connective tissue and smooth muscles. Also contains rete ovarii which is a solid cellular cords or networks of irregular channels lined by cuboidal epithelium.  Ovarian Follicles Primordial follicle: Unilaminar, preantral,resting follicle. Comprises of primary oocyte surrounded by simple squamous epithelium.  Ovarian Follicles Primary follicle: Unilaminar, preantral, growing follicle. Comprises of primary oocyte surrounded by simple cuboidal epithelium.  Ovarian Follicles Early Secondary follicle: Multilaminar, preantral, growing follicle. Comprises of primary oocyte surrounded zona pellucida and stratified epithelium of polyhedral/ follicular cells called as Granulosa cell. Zona pellucida is a glycoprotein layer  Ovarian Follicles Late Secondary follicle: Multilaminar, antral, growing follicle. Comprises of primary oocyte surrounded by zona pellucida and stratified epithelium of polyhedral/ follicular cells called as Granulosa cell (Zona Granulosa) with an outer covering of theca interna. Antral pockets are formed containing liquor folliculi. Theca layer (Theca interna) comprises of vascularized multilaminar layer of spindle shaped stroma cells.  Uterine Tubes Also called the Fallopian tube or oviduct, the oviduct is an essential part of the female reproductive system that connects the ovary to the uterus. Histological Features: The Uterine Tubes are lined with simple columnar or pseudostratified columnar epithelium containing motile cilia. Both ciliated and non-ciliated cells possess microvilli. Lamina Propria-Submucosa: This layer consists of loose connective tissue containing numerous plasma cells, mast cells, and eosinophils. Notably, the lamina muscularis is absent. Tunica Mucosa: In the ampulla, the mucosa is highly folded, forming primary, secondary, and tertiary folds. In the isthmus, only primary folds are present.  Uterine Tubes Tunica Muscularis: Composed of inner circular smooth muscle fibers, with isolated bundles of longitudinal and oblique fibers. Tunica Serosa: The outermost layer is a reflection of the peritoneum, comprising fibrous connective tissue covered by mesothelium. It contains numerous blood vessels and nerves for vascular and neural supply.  Uterus The uterus, or womb, is a vital organ of the female reproductive system, playing a crucial role in pregnancy, childbirth, and the menstrual cycle. It is positioned above the vagina, between the bladder and rectum, and is held in place within the pelvis by several ligaments. Structurally, it is about 7 cm long and 5 cm wide at its broadest point.  Uterus Perimetrium (Tunica serosa): Consists of loose connective tissue covered by mesothelium, few smooth muscle cells, lymphatics, blood vessels and nerves. Myometrium (Tunica muscularis): Consists of thick inner circular layer and outer longitudinal layer of smooth muscles. In between these two layers stratum vasculare is present. Endometrium (Tunica mucosa and submucosa): The inner layer of the uterus, it contains simple tubular glands lined by columnar epithelium and is richly vascularized by spiral arteries that adapt during the menstrual cycle. PLACENTA: OVERVIEW Organ formed from fetal (chorion frondosum) and maternal (decidua basalis) tissues. Vital organ formed during pregnancy, facilitating exchange between mother and fetus. Provides nourishment, oxygen, and protection for fetal development. Transports nutrients (glucose, amino acids, oxygen) to fetus; removes waste (carbon dioxide, metabolic waste). Produces hormones (hCG, progesterone, estrogen) to support pregnancy. Offers immunological defense, allowing maternal antibodies to protect the fetus. PLACENTA Structure and Surfaces 1. Fetal Portion: Formed by the chorion frondosum. Includes the chorionic villi, containing fetal capillaries for exchange with maternal blood. Chorionic Plate (Fetal Surface): Covered by the amnion, secreting amniotic fluid for fetal cushioning and exchange facilitation. The chorion, deep to the amnion, is continuous with the uterine lining. Initially covered in villi, which develop into the chorion frondosum. 2. Maternal Portion: Formed by the decidua basalis. Basal Plate (Maternal Surface): Forms during placental separation from the uterine wall. Contains decidua basalis, decidua capsularis, and parietal decidua. Decidua Basalis modified endometrium composed of decidua cells Decidual cell site of maternal blood Chorionic Villi fetal processes that invade the decidua basalis & contain fetal blood vessels Key Specialized Cells in the Placenta: 1. Decidual Cells: Derived from endometrial stromal cells, located in the decidua basalis. 2. Hofbauer Cells: Fetal macrophages in the villous stroma, involved in immune defense. 3. Trophoblastic X-Cells: Found in the basal plate; secrete parathyroid hormone-related protein (PTHrP). 4. Cytotrophoblasts: Mononuclear precursor cells to other trophoblasts. 5. Syncytiotrophoblasts: Multinucleated epithelial layer covering villous trees and chorionic villi. Formed by fusion of trophoblasts; facilitates maternal-fetal exchange and secretes hCG.  The Blood- Placental Barrier Serves as the boundary between maternal and fetal circulations. Ensures selective exchange of gases, nutrients, and waste while protecting the fetus from harmful substances. Mesenchymal Fetal Endothelial Syncytiotrophoblast Cytotrophoblast: Connective Tissue: Cells Outermost layer formed by Layer beneath Provides structural support Line fetal capillaries inside fusion of cytotrophoblasts. syncytiotrophoblast. within chorionic villi. chorionic villi. Facilitates implantation by Contributes to placental Facilitate exchange between eroding maternal tissue. structure and supports the maternal and fetal blood. Secretes hCG to support syncytiotrophoblast. pregnancy.  Functional Significance During Pregnancy Human Chorionic Gonadotropin (hCG): First hormone produced by the placenta. Maintains the corpus luteum in early pregnancy to produce progesterone. Progesterone: Prevents uterine contractions to sustain pregnancy. Maintains the uterine lining. Prepares breasts for lactation. Later produced directly by the placenta as pregnancy progresses. Estrogen: Promotes uterine growth. Increases uterine blood flow. Stimulates mammary gland development for breastfeeding. Overall Importance: Maintains pregnancy. Supports fetal growth. Prepares the mother’s body for labor and breastfeeding.  VAGINA The vagina is a fibromuscular tube connecting the uterine cavity to the external environment. Functions: Menstruation, childbirth, and sexual activity. Layers of the Vagina Layers of the Vagina Mucosa: Lined with non-keratinized stratified squamous epithelium for protection against mechanical stress. Contains lamina propria (loose and dense connective tissue, collagen fibers). Lacks glands; lubrication provided by cervical mucus. Highly vascularized for nourishment and hormone responsiveness. Muscularis: Smooth muscle fibers interspersed with connective tissue. Provides elasticity and contractility for childbirth and sexual activity. Adventitia: Outermost connective tissue layer. Anchors the vagina to surrounding structures (pelvic wall and perineum). Provides structural stability. EXTERNAL GENITALIA Lies external to hymen and is limited by mons pubis anteriorly, anus posteriorly and inguinal gluteal folds laterally Structures: Includes the mons pubis, labia majora, labia minora, clitoris, vestibule, Bartholin's glands, and Skene's glands. Functions: Protection, sexual function, and childbirth. Histology of Vulvar Structures: Mons Pubis: Tissue Composition: Subcutaneous adipose tissue covered with skin and hair. Epithelium: Keratinized stratified squamous epithelium for protection. Histology of Vulvar Structures: Labia Majora: Tissue Composition: Adipose tissue, smooth muscle, sweat glands, and sebaceous glands. Epithelium: Keratinized stratified squamous epithelium for durability and moisture. Histology of Vulvar Structures: Labia Minora: Tissue Composition: Loose connective tissue, rich in sebaceous glands (no hair follicles). Epithelium: Non-keratinized stratified squamous epithelium for flexibility and sensitivity. Histology of Vulvar Structures: Clitoris: Tissue Composition: Erectile tissue (corpora cavernosa). Epithelium: Highly vascularized and richly innervated tissue. Vestibule: Epithelium: Non-keratinized stratified squamous epithelium. Glands: Includes Bartholin’s and Skene’s glands for lubrication and protection. General Vulvar Skin: Varies in keratinization: Keratinized on mons pubis and labia majora; non- keratinized on labia minora and vestibule. Underlying Dermis: Rich in blood vessels, nerve endings, melanocytes, Langerhans cells (immune response), and Merkel cells (touch sensation). Functions of Glands: Bartholin’s Glands: Secrete mucus for lubrication during sexual arousal. Skene’s Glands: Contribute to lubrication and potential antibacterial protection. Hormonal Influence on Histology: Estrogen: Thickens epithelium, increases vascularity (especially during reproductive years). Progesterone: Enhances lubrication and maintains epithelial changes during pregnancy. Common Disorders: 1. Vulvovaginitis: Inflammation of vulva and vagina. Causes: infections, irritants, or allergies. Symptoms: itching, redness, and discharge. 2. Bartholin’s Gland Cysts: Blockage in Bartholin’s glands, forming fluid-filled cysts. May lead to abscesses if infected. Common Disorders: 3. Lichen Sclerosus: Chronic skin condition causing thin, white, fragile skin. Common in postmenopausal women. 4. Vulvar Intraepithelial Neoplasia (VIN): Precancerous condition linked to HPV. Presents as skin patches, itching, or pain. 5. Vulvar Cancer: Rare, most common in older women. Symptoms: lumps, itching, pain, or skin changes.  MAMMARY GLANDS Classification and Structure: Mammary glands are compound tubular alveolar exocrine glands with branching ducts and alveoli. Organized into lobes, lobules, and ducts: Lobes: Larger divisions collecting milk from lobules. Lobules: Contain alveoli, the milk- producing units. Ducts: Transport milk to the nipple.  MAMMARY GLANDS Inactive State (Non-pregnant): Alveoli are underdeveloped and non- functional. Abundant connective tissue The sparse glandular component consists chiefly of ducts. Ducts are surrounded by a loose connective tissue containing lymphocytes, plasma cells and fibroblasts. The ducts and surrounding loose connective tissue constitute a lobule. Beyond a lobule, the connective tissue is more dense The dense connective tissue contains aggregates of adipocytes.  MAMMARY GLANDS Inactive State (Non-pregnant): Alveoli are underdeveloped and non- functional. Abundant connective tissue The sparse glandular component consists chiefly of ducts. Ducts are surrounded by a loose connective tissue containing lymphocytes, plasma cells and fibroblasts. The ducts and surrounding loose connective tissue constitute a lobule. Beyond a lobule, the connective tissue is more dense The dense connective tissue contains aggregates of adipocytes. MAMMARY GLANDS Active State (Pregnancy): Alveoli undergo hyperplasia, becoming more numerous and developed. Glandular tissue increases, replacing adipose tissue. Increased vascularity supports the metabolic demands of milk production. MAMMARY GLANDS Active State (Pregnancy): Individual lobules are separated by narrow dense connective tissue septa The connective tissue within a lobule is loose connective tissue that is now containing more lymphocytes and plasma cells. The ducts and alveoli are well developed, secretory products may be seen in the lumen Alveoli show irregular branching pattern  References: DaVinci Academy. (2023, May 24). Histology of uterus and cervix [Female Reproductive Histology Part 2 of 2] [Video]. YouTube. https://www.youtube.com/watch?v=m0w1Ot0fGMs Dr. Iman Nabil Histology for medical students. (2022, September 10). Histology of Female external genitalia- Female genital system [Video]. YouTube. https://www.youtube.com/watch?v=LXH1-oYihFQ Histology of the female reproductive system. (2024, January 18). Kenhub. https://www.kenhub.com/en/library/anatomy/histology-of-the- female-reproductive-system? fbclid=IwY2xjawGpLh5leHRuA2FlbQIxMAABHT28Ni68ksIqOsuKSBOpY7j5Rd40qjBkJNk8s1Mt9YqG26R9f-twQwq- 9A_aem_OoNQEpOm0WkCJB6jr2OgbQ Marieb, E. N., & Hoehn, K. (2019). Human anatomy & physiology (11th ed.). Pearson. Mescher, A. L. (2015). Junqueira’s basic histology: Text and Atlas. Nguyen, J.D., & Duong, H. (2021). Anatomy, Abdomen and Pelvis, Female External Genitalia. In StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK547703/ Ninja Nerd. (2021, February 13). Embryology | Development of reproductive system [Video]. YouTube. https://www.youtube.com/watch? v=eKuO_526YCc Williams, C. J., & Erickson, G. F. (2012, January 30). Morphology and physiology of the ovary. Endotext - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK278951/?fbclid=IwY2xjawGpLr1leHRuA2FlbQIxMAABHWvwCt- _ym0tBZtiaqzQsoLvpLgOReJgVN38iqGipaT0-0H0D54zKiV1pw_aem_oQvrVbyL2_JO9w9uZmqwZw  5 6 4 7 3 8 2 9 1 10 28 11 27 12 26 TYSM! 13 25 14 24 15 23 16 22 17 21 18 20 19