Histology: Female Reproductive System

early secretory phase

Luteal (Secretory Phase): Occurs within a few days after ovulation Glands enlarge and become tortuous Secretory products increase Fibroblasts of the stroma accumulate glycogen and fat

This particular thick, muscle layer of the uterus contains large blood vessels and it is where hypothalamic oxytocin promotes intermitting contractions during labor and infant delivery: A. Adventitia B. Endometrium C. Fundus D. Myometrium E. Perimetrium

d

Genital and Reproductive Structures internal vs external

INTERNAL Ovaries Uterine Tubes Uterus Vagina EXTERNAL Mons Pubis (subcutaneous adipose tissue) Labia Majora and Minora Clitoris (sensory nerve endings) Vestibule and Opening of the vagina (stratified squamous epithelium) Hymen (mucous membrane) External Urethral Orifice They are contained mainly within the pelvic cavity and in the perineum (from the coccyx [tail bone] to the pubis and below the pelvic diaphragm)

Female External Genitalia labia majora labia minora

LABIA MAJORA: Squamous epithelium Smooth muscle Adipose tissue Hair cells Sebaceous glands Sweat glands LABIA MINORA: Squamous epithelium Connective tissue Blood vessels Elastic fibers Sebaceous glands

The Female Clitoris: Histology Erectile structure Homologous to the penis Composed of two erectile bodies: Corpora cavernosa: Spongy tissue Tunica albuginea: Fibrous sheath Numerous sensory nerve endings Meissner's corpuscles Pacinian corpuscles Richly supplied by blood vessels

Meissner tactile corpuscles: are specialized to detect light touch Lamellated (pacinian) corpuscles: detect coarse touch or pressure Corpus spongiosum in erection is to prevent the urethra from pinching closed, thereby maintaining the urethra

Histology of the Ampulla: (H&E)

Mucosa (with Peg cells and ciliated cells). The underlying connective tissue is the lamina propria

Mammary Glands: Essential Features

Secretory Alveoli (Lactating Gland): A network of contractile myoepithelial cells Progesterone-induced secretory changes Alveoli become filled with their own secretion: COLOSTRUM Colostrum: Protein-rich first milk Prolactin, Oxytocin, hypothalamic dopamine

Fertilization normally occurs in the upper region of the: A. Fundus B. Cervix C. Ampulla D. Theca interna E. Corpora cavernosa

c

Identify structure (asterisk) in the attachment. This is the remnant of the degenerated corpus luteum: A. Antrum B. Atretic follicle C. Corpus albicans D. Ovarian cortex E. Ovarian medulla

c

The secretory phase of the menstrual cycle is regulated by: A. Estrogen B. Relaxin C. Progesterone D. Luteinizing hormone E. Follicle stimulating hormone

c

Successfully fertilization typically occurs: A. At the newly transformed corpus hemorrhagicum B. At the ovarian ligament C. At the theca externa and connective tissue layer D. At the uterine tube's ampullaroisthmic junction E. At the zona pellucida (ZP-3) coating

d

Identify ovarian structure (asterisk) in the attachment. The fluid-filled spaces of this structure contain various hormone (e.g., estradiol, inhibin and progesterone) and eventually coalesce to form a single large cavity: A. Antrum B. Corpus albicans C. Corpus hemorrhagicus D. Infundibulum E. Ovum

A

Histology of the Uterus (H & E)

Endometrium (inner most): Mucosa of the uterus Epithelial cells Cells undergo hormonally modulated cyclic changes during the menstrual cycle Stages: Follicular, Luteal and Menstrual Myometrium (intermediate): Thick, muscular layer Layers of smooth muscle fibers Contains relatively large blood vessels Oxytocin: promotes myometrial contractions Perimetrium (outer serous): Very thin layer of mesothelium (loose connective tissue) Follicular (Proliferative Phase:) Endometrial surface is re-epithelialized Glands, connective tissue and vascular supply are re-established

The Menstrual Cycle: An Overview

HYPOTHALAMUS: Secretes Kiss1 and GnRH PITUITARY GLAND: Secretes FSH and LH FSH and LH stimulate follicle growth The follicles start to make ESTRADIOL Several follicles begin to grow with each cycle Day 12: Estradiol levels rise steeply Estradiol surge stimulates a LH surge (positive feedback) The LH surge triggers ovulation Follicle ruptures, releasing the secondary oocyte Follicle left in the ovary forms the corpus luteum (CL): Secretes progesterone and estradiol Rising progesterone and estradiol levels stimulate HYPOTHALAMUS: Secretes Kiss1 and GnRH PITUITARY GLAND: Secretes FSH and LH FSH and LH stimulate follicle growth The follicles start to make ESTRADIOL Several follicles begin to grow with each cycle Day 12: Estradiol levels rise steeply Estradiol surge stimulates a LH surge (positive feedback) The LH surge triggers ovulation Follicle ruptures, releasing the secondary oocyte Follicle left in the ovary forms the corpus luteum (CL): Secretes progesterone and estradiol Rising progesterone and estradiol levels stimulate thickening of the endometrium (uterine wall) If pregnancy occurs: CL continues secreting progesterone and estradiol to maintain the endometrium If pregnancy does not occur: CL disintegrates and hormone levels drop Results in the loss of endometrial tissue (menstrual flow)thickening of the endometrium (uterine wall) If pregnancy occurs: CL continues secreting progesterone and estradiol to maintain the endometrium If pregnancy does not occur: CL disintegrates and hormone levels drop Results in the loss of endometrial tissue (menstrual flow) This continues for ~ 450 cycles, then women enter menopause

Mammary Glands

Highly modified sweat glands Are made up of 15 to 25 lobes Each lobe represents a compound alveolar gland with a lactiferous duct The stromal fibrous tissue that connects the lobe contains abundant adipose tissue when the breast is in the non-lactating condition Proliferative and secretory changes occur at pregnancy in response to high levels of estrogen, progesterone, prolactin and chorionic somatomammotropin hormones Mature breast tissue that has not yet undergone the secretory response is known as the resting (inactive) breast Lactiferous ducts are lined up by cuboidal to columnar epithelium (the outer most layer represent contractile myoepithelial cells) There is also interlobular connective tissue in which the lobules lie scattered

Histology of the Isthmus: (H&E)

Narrow region that connects to the uterus at the interstitial (intramural) region SEROSA: Outer layer Visceral peritoneum with mesothelium. Squamous epithelium + connective tissue MUSCULARIS: Inner circular and outer muscular layers Smooth muscle MUCOSA: Lamina propria-connective tissue from to muscularis Simple columnar epithelium

Histology of the Infundibulum: (H&E)

Normal adult fallopian tube has a thin outer smooth muscular coat composed of ill-defined inner circular and outer longitudinal layers, and an inner complex branching pattern of finger-like projections of connective tissue lined by epithelial cells seen here at low magnification. The fallopian tubes conduct spermatozoa upward and ova downward to the endometrial cavity Ampulla. Tunica Mucosa; Tunica Muscularis; Lumen; Tunica Serosa .

Endometrium: Proliferative and Secretory Phases

Note the early coiling and synchronously developed glands Glands (G) are relatively straight, narrow, and empty. The tubular glands have wider lumens containing secretory product and coil tightly up through the stroma, giving a zigzag or folded appearance histologically

Fallopian Tube Walls: Mucosa Layer PEG CELLS (PC): Unciliated Secrete a nutritive fluid that facilitates capacitation of spermatozoa Nourishes embryo as it passes down Fallopian tubes Inhibits microorganisms that could invade from the peritoneal cavity CILIATED CELLS (CC): Generates flow toward uterus Estrogen sensitive Cilia beat toward uterus Spermatozoa must swim upstream

PEG CELLS (PC): Unciliated Secrete a nutritive fluid that facilitates capacitation of spermatozoa Nourishes embryo as it passes down Fallopian tubes Inhibits microorganisms that could invade from the peritoneal cavity CILIATED CELLS (CC): Generates flow toward uterus Estrogen sensitive Cilia beat toward uterus Spermatozoa must swim upstream

Fallopian Tubes

Paired tubes that extend bilaterally from the uterus toward the ovaries Also termed oviducts, uterine tubes Divided into four segments: Infundibulum Ampulla Isthmus Uterine (Intrastitial) part Region through the infundibulum (bottom photomicrograph). Note the long mucosal folds The oviduct consists of several segments: •Infundibulum, which contains fimbriae and is located adjacent to the ovary, the ampulla, the isthmus, and the pars interstitialis. •Fimbriated (fringe) end that scans the ovary and captures the secondary oocyte •The first two of these regions have a characteristic appearance that is dominated by an elaborate mucosa that is thrown into numerous branched folds, surrounded by a relatively thin layer of smooth muscle. • As the tube moves away from the ovary and toward the uterus, these folds become smaller and the smooth muscle dominates.

The Ovary: Anatomy and Histology

Production of gametes and steroid hormones (Estrogens and Progesterones) Oogenesis Composed of a CORTEX and a MEDULLA CORTEX: Rich in ovarian follicles MEDULLA: Highly vascular structure TUNICA ALBUGINEA: THICK CONNECTIVE TISSUE CAPSULE Covered by the germinal epithelium Simple squamous to cuboidal mesothelium

Which of the following hormones regulates the proliferative phase of the menstrual cycle? A. Estrogen(s) B. Progesterone(s) C. Oxytocin D. Prolactin E. Hypothalamic dopamine

Rationale: a. Correct. Estrogens regulate the proliferative phase of the me menstrual cycle b. Incorrect. Progesterone maintains pregnancy c. Incorrect. Oxytocin promotes contractions of the uterus d. Incorrect. Prolactin is involved in lactating breasts e. Incorrect. Hypothalamic dopamine in inversely associated with pituitary prolactin

Identify A and B sub-regions of the human ovary depicted: (see attachment) A. A = cortex; B = medulla B. A = tunica albuginea; B = germinal epithelium C. A = zona pellucida; B= theca interna D. A = medulla; B = cortex E. A = corona radiata; B = cumulus oophorous

Rationale: a. Incorrect. A points to the medulla, whereas B points to the cortex. b. Incorrect. A points to the medulla, whereas B points to the cortex. c. Incorrect. A points to the medulla, whereas B points to the cortex. d. Correct. A points to the medulla, whereas B points to the cortex. e. Incorrect. A points to the medulla, whereas B points to the cortex.

At parturition, which of the following tissues undergoes powerful contractions triggered by the hormone oxytocin? A. Endometrium B. Myometrium C. Adventitia D. Perimetrium E. Fundus

Rationale: a. Incorrect. Endometrium is important in the cyclic shedding of the stratum functionale b. Correct. Myometrium is targeted by the actions of oxytocin which help expel the fetus c. Incorrect. Adventitia is loose connective tissue d. Incorrect. Perimetrium is loose connective tissue e. Incorrect. Fundus is part of the uterus

Which of the following peptides regulates the pulsatile secretion of hypothalamic GnRH? A. FSH B. LH C. Kiss 1 D. AVP (arginine vasopressin) E. Oxytocin

Rationale: a. Incorrect. FSH is activated by hypothalamic GnRH b. Incorrect. LH is activated by hypothalamic GnRH c. Correct. Kiss 1 peptide regulates the cyclic secretion of hypothalamic GnRH d. Incorrect. Hypothalamic AVP targets distal components of the kidneys e. Incorrect. Oxytocin triggers parturition

Which of the following molecules regulate the pulsatile secretion of hypothalamic gonadotropin- releasing hormone (GnRH)? A. Ghrelin B. Leptin C. Kisspeptin D. AVP E. Oxytocin

Rationale: a. Incorrect. Ghrelin is secreted by the stomach prior to food intake. b. Incorrect. Leptin is produced by brown adipose tissue; it targets hypothalamic neurons during the course of food intake. c. Correct. Kisspeptin is a hypothalamic hormone encoded by the KISS1 gene; it regulates the cyclic secretion of GnRH from the brain. d. Incorrect. Arginine vasopressin (AVP) is a hypothalamic hormone that stimulates water reabsorption by the renal medullary collecting ducts. e. Incorrect. Oxytocin is a hypothalamic peptide that stimulates milk ejection by the mammary glands; it also stimulates uterine smooth muscle contraction during copulation and childbirth.

Which of the following ovarian receptors is essential for mammalian fertilization? A. Izumo1 B. AR C. Ryanodine D. Juno E. PPAR

Rationale: a. Incorrect. Izumo 1 is an essential sperm cell-surface protein. b. Incorrect. Androgen receptor (AR) is an intracellular protein found in many cell-types, including the prostate gland. c. Incorrect. Ryanodine is a calcium-permeable receptor. d. Correct. Juno is the egg izumo receptor and is essential for mammalian fertilization. e. Incorrect. Peroxisome proliferator-activated receptor (PPAR) is a nuclear protein that regulates gene expression; PPARs agonists are used to treat diabetes and elevated blood lipids.

Which of the following structures transforms itself into a temporary endocrine organ after ovulation? A. Theca interna B. Corpus albicans C. Corpus luteum D. Corona radiata E. Zona pellucida

Rationale: a. Incorrect. Theca interna is a layer of cells that contain androgen-secreting cuboidal cells b. Incorrect. Corpus albicans replaces a degenerated corpus luteum c. Correct. Corpus luteum is a temporary endocrine gland formed by the remnants of a follicle d. Incorrect. Corona radiata is a layer of follicle cells that surround Graafian follicles e. Incorrect. Zona pellucida forms between the oocyte and follicle cells

The Vagina: Fibromuscular Tube Mucosa (inner): STRATIFIED SQUAMOUS EPITHELIUM Glycogen-rich Vascular cavernous spaces (typical erectile tissue) Muscularis (intermediate): Smooth muscle: longitudinal & circumferential Adventitia (outer): Contains many elastic fibers Loose connective tissue with a prominent venous plexus

The lumen of the vagina is lined by a NONKERATINIZED, STRATIFIED, SQUAMOUS EPITHELIUM (mucosal type) Resting on a prominent basal lamina and an underlying lamina propria STRATIFIED SQUAMOUS EPITHELIUM: Flat eosinophilic cells; many leukocytes LAMINA PROPRIA: loose fibroelastic connective tissue, richly vascular

Follicular Atresia

Very few ovarian follicles that begin their differentiation in the embryonic ovary are destined to complete their maturation Most ovarian follicles are lost by ATRESIA Degenerative process that can occur at any stage of follicular development. Degeneration of the oocyte Hypertrophy of the thecal cells and autolysis of the granulosa cells OVARIAN FOLLICULAR ATRESIA: Mediated by apoptosis of granulosa cells

Vaginal Epithelium: Menopause

Vulvovaginal atrophy: During perimenopause, less estrogen may cause the tissues of the vulva and the lining of the vagina to become thinner, drier, and less elastic or flexible