Lecture 16: Histology of the Reproductive System

• This lecture discusses the histology of the male and female reproductive systems
• It includes the microanatomy of the ovaries, uterus, cervix, vagina, mammary glands, testes, and penis
• It also explains the cyclical changes of the endometrium and spermatogenesis

Learning points

• Successful students should be able to identify tissues and cells of the male and female system in histological sections
• Should be able to describe the function of the tissues and cells
• Be able to describe and identify the stages of oogenesis and spermatogenesis

Female Reproductive System

Ovaries

• Ovaries have two main functions: gametogenesis (oogenesis) and steroidogenesis
• Steroidogenesis involves the production of estrogen and progestogens
• The ovary has a medulla and cortex
• The medulla is composed of loose connective tissue, blood and lymph vessels and nerves
• The cortex contains ovarian follicles
• The ovary is covered by germinal epithelium, not mesothelium
• Deep to the epithelium is a dense connective tissue layer called the tunica albuginea
• 70% of ovarian cancers originate from the epithelium

Oogenesis

Primordial follicles

• Primordial follicles first appear in the 3rd month of fetal development
• A single layer of squamous follicle cells surrounds the oocyte
• These follicles are surrounded by a basal lamina

Early Primary Follicle

• Has an extracellular coat called the zona pellucida
• Follicle cells are cuboidal
• Glycoproteins in the zona pellucida bind to spermatozoa

Late Primary Follicle

• Features a zona pellucida made of extracellular coat
• Has several layers of follicle cells, called the granulosa layer
• A basal lamina surrounds the granulosa layer
• Thecal layer is present
• Theca interna contains secretory cells, an inner vascular layer, and a large number of LH receptors
• Theca externa is composed of mainly smooth muscle cells and bundles of collagen fibers

Secondary Follicle

• Develops when granulosa cells reach 6-12 layers, forming the stratum granulosum
• Fluid-filled antrum forms
• Oocyte and follicular growth are stimulated by FSH and other growth factors

Mature (Graafian) Follicle

• Granulosa cells project into the antrum as the cumulus oophorus
• The cells surrounding the oocyte will become the corona radiata during ovulation

Ovulation

• Occurs when secondary oocyte is released from the Graafian follicle
• The follicular stigma (macula pellucida) becomes elevated and then ruptures

Corpus Luteum

• Happens after ovulation, when the follicular wall (granulosa and thecal cells) becomes the corpus luteum
• Luteal cells increase in size, filling with lipid droplets
• Granulosa lutein cells secrete estrogen, progesterone, and inhibin
• Theca lutein cells secrete androgens and progesterone
• If the oocyte is not fertilized, there is no hCG production
• Progesterone and estrogen levels decrease
• The corpus luteum degenerates into the corpus albicans

Uterine Tubes

• Consist of serosa or peritoneum composed of mesothelium and a thin layer of connective tissue
• Muscularis has a thick inner circular layer and a thin outer longitudinal layer
• Mucosa features folds that project into the lumen and contains connective tissue and blood vessels

Uterine Tube Mucosa

• Consists of ciliated cells that are the most numerous and direct wave of cilia towards the uterus
• Has nonciliated peg cells, which are secretory cells that produce nutrition for the ovum or zygote

Uterus

• Uterus contains endometrium, myometrium and perimetrium
• Endometrium is the mucosa of the uterus
• Myometrium is a thick muscular layer
• Perimetrium is the outer serous layer/visceral peritoneal covering

Endometrium

• Has two layers: stratum functionale and stratum basale
• Stratum functionale is the thick part sloughed off at menstruation
• It is composed of simple columnar epithelium and uterine glands
• Stratum basale regenerates the stratum functionale

Vasculature of Endometrium

• Radial branch gives off spiral artery in stratum basale
• Thin-walled dilated segments called lacunae make up the capillary bed

Changes During Menstrual Cycle

• Proliferative phase: Occurs with follicular maturation
• Secretory phase: Coincides with functional activity of corpus luteum
• Menstrual phase: Reduction of hormone production occurs due to degeneration of the corpus luteum

Cervix

• Has cervical mucosa with large cervical glands
• Secretions vary throughout menstrual cycle being less viscous at mid-cycle
• At other times, the cervical secretions prevent sperm from entering the uterus

Transformation Zone

• This is between the endocervix (simple columnar) and the ectocervix (stratified squamous)

Vagina

• Mucosa has transverse folds of CT, (nonkeratinized) stratified squamous epithelium
• Muscularis has outer longitudinal and inner circular layers
• Adventia has an inner elastic layer and an outer layer with neurovasculature and lymph

Mammary Glands

• Consist of modified tubuloalveolar sweat glands (apocrine)
• Have ductules (acini), which are secretory alveoli producing milk when active
• Lactation involves both merocrine and apocrine secretion
• Merocrine secretion is protein production by the rER
• Apocrine secretion is a lipid component with lipid droplet free in the cytoplasm

Male Reproductive System

Testis

• Functions in spermatogenesis (sperm) and steroidogenesis (testosterone)
• Tunica vaginalis which is continuation of peritoneum
• Tunica albuginea is a thick, dense connective tissue layer
• Has tunica vasculosa, which is inner to albuginea, it's made of loose connective tissue with blood vessels
• Consists of Sperm production occurs in Seminiferous tubules are the site of sperm production, separated into lobules (~250) by septa (capsule extensions)

Seminiferous Tubules

• Have two cell populations: Sertoli and Spermatogenic cells
• Sertoli cells are supporting or sustentacular cells
• They do not replicate after puberty
• Columnar cells with apical and lateral processes
• Spermatogenic cells replicate and differentiate into mature sperm cells

Spermatogenesis

• Phase 1: Spermatogonial phase; spermatogonia divide via mitosis to replace themselves
• Phase 2: Spermatocyte phase; primary spermatocytes undergo meiotic divisions to reduce chromosome number
• Phase 3: Spermatid phase; spermatids differentiate into mature sperm

Spermiogenesis

• Golgi phase: acrosomal vesicle forms; axoneme initiated
• Cap phase: acrosomal vesicle becomes acrosomal cap; nucleus condenses
• Acrosome phase: manchette forms & disappears; neck, middle piece & tail form
• Maturation phase: cytoplasm is extruded

Stages of Seminiferous Epithelium

• There are six stages in human
• It takes 4.6 cycles for a spermatogonium stemming from a stem cell to complete the process which is approximately 74 days

Sertoli Cells

• Columnar epithelial cells that divide the seminiferous tubules into basal and luminal compartments
• Tight occluding junctions form blood-testis barrier
• This prevents immune attacks on unique spermatogenic cells
• The cells support, protect, provide nutrition, and exocrine and endocrine secretion
• Secrete ABP, Inhibin and Müllerian-inhibiting substance (MIS)
• Phagocytose excess cytoplasm from spermiogenesis

Leydig Cells

• Hormone (testosterone mostly) producing
• Large, polygonal, eosinophilic cells with lipid droplets
• Has lots of ER (which accounts for eosinophilic nature)

Rete Testis

• Transition from seminiferous tubule
• Simple cuboid epithelium

Epididymis

• Site of sperm maturation
• Contains efferent ductules with pseudostratified columnar epithelium
• Principal cells have stereocilia
• Basal cells are round resting cells

Ductus Deferens

• Lined with pseudostratified columnar epithelium and has sterocilia
• Has basal cells
• Lumen does not appear smooth (unlike epididymis)
• Longitudinal fold
• Muscular has muscular layers

Seminal Vesicle

• Wall has mucosa, thin layer of smooth muscle, and fibrous coat
• Mucosa is pseudostratified columnar epithelium and it has numerous folds
• Secretions contain fructose energy and prostaglandins which stimulate activity in the female system

Prostate

• Composed of four zones: central, peripheral, transitional, periurethral
• Central zone: Surrounds ejaculatory ducts, 25% of the glandular tissue
• Peripheral zone: 70% of glandular tissue, common site of cancer
• Transitional zone: Surrounds urethra, 5% of glandular tissue, site of benign prostatic hyperplasia (BPH)
• Periurethral zone: mucosal and submucosal glands
• Contains tubuloalveolar glands, smooth muscle, and a connective tissue
• Contains Prostatic concretions; secretes alkaline fluid; contains prostate specific antigen (PSA): serine protease
• Features prostatic acid phosphatase (PAP) and Fibrinolysin

Penis

• Contains erectile tissue with corpora cavernosa and corpus spongiosum
• Irregularly shaped vascular spaces with smooth muscle
• Fibroelastic layer is known as the Tunica albuginea