Male Reproductive System Anatomy and Physiology
Male Reproductive System
Overview
The male reproductive system consists of:
Testes
Genital ducts
Accessory glands
Penis
Testes
Produce sperm.
Contain endocrine cells secreting hormones like testosterone.
Testosterone drives male reproductive physiology.
Important for spermatogenesis.
Sexual differentiation during embryonic and fetal development.
Control of gonadotropin secretion in the pituitary.
Dihydrotestosterone (a metabolite of testosterone) acts on many tissues during puberty (e.g., male accessory glands and hair follicles).
Each testis is surrounded by a dense connective tissue capsule called the tunica albuginea.
Thickens on the posterior side to form the mediastinum testis.
Septa penetrate the organ from this fibrous region, dividing it into about 250 pyramidal compartments or testicular lobules.
Each lobule contains:
Sparse connective tissue with endocrine interstitial cells (Leydig cells) secreting testosterone.
One to four highly convoluted seminiferous tubules where sperm production occurs.
Testes develop retroperitoneally in the dorsal wall of the embryonic abdominal cavity and move during fetal development to become suspended in the scrotal sac (scrotum).
Suspended at the ends of the spermatic cords.
During migration, each testis carries a serous sac, the tunica vaginalis, derived from the peritoneum.
Outer parietal layer lining the scrotum.
Inner visceral layer covering the tunica albuginea on the anterior and lateral sides of the testis.
Temperature Regulation
Sperm formation requires a permissive temperature of about , lower than the core body temperature of .
Mechanisms for temperature regulation:
Pampiniform venous plexus: surrounds each testicular artery, containing cooler blood from the testis.
Draws heat from the arterial blood by a countercurrent heat-exchange system.
Evaporation of sweat from the scrotum.
Dartos muscle of the scrotum and cremaster muscles of the spermatic cords:
Move the testes away from or closer to the body, respectively, for further temperature control.
Medical Applications
Hydrocele: Excessive accumulation of serous fluid in one or both sides of the scrotal sac.
Most common cause of scrotal swelling and can be corrected surgically.
Cryptorchidism: Failure of one or both testes to descend from the abdomen.
Occurs in about 4% of male neonates.
Bilateral cryptorchidism causes infertility if not surgically corrected by 2 to 3 years of age.
Germ cell tumors appears at a higher rate if cryptorchidism isn't treated.
Interstitial Tissue
Located between the seminiferous tubules.
Consists of sparse connective tissue containing fibroblasts, lymphatics, and blood vessels (including fenestrated capillaries).
Interstitial cells (Leydig cells) develop during puberty.
Large round or polygonal cells with central nuclei and eosinophilic cytoplasm rich in small lipid droplets.
Produce the steroid hormone testosterone, which promotes development of the secondary male sex characteristics.
Testosterone is synthesized by enzymes present in the smooth ER and mitochondria.
Testosterone secretion is triggered by the pituitary gonadotropin, luteinizing hormone (LH), also called interstitial cell stimulating hormone (ICSH).
In the late embryonic testes, gonadotropin from the placenta stimulates interstitial cells to synthesize testosterone.
Needed for development of the ducts and glands of the male reproductive system.
Fetal interstitial cells are very active during the third and fourth months of pregnancy, then regress and become quiescent cells until puberty.
Medical Applications
Interstitial cell tumors and Sertoli cell tumors are rare.
Most (95%) testicular cancer involves germ cell tumors, which only appear after puberty and are much more likely to develop in men with untreated cryptorchidism.
Seminiferous Tubules
Sperm are produced here at a rate of about per day in the young adult.
Each testis has from 250 to 1000 tubules in its lobules.
Each tubule measures 150-250 μm in diameter and 30-70 cm in length.
The combined length of the tubules of one testis totals about 250 m.
Each tubule is a loop linked by a very short, narrower segment, the straight tubule, to the rete testis.
Rete testis: labyrinth of epithelium-lined channels embedded in the mediastinum testis.
About 10-20 efferent ductules connect the rete testis to the head of the epididymis.
Each seminiferous tubule is lined with a complex, specialized stratified epithelium called germinal or spermatogenic epithelium.
The basement membrane of this epithelium is covered by fibrous connective tissue, with an innermost layer containing flattened, smooth muscle-like myoid cells, which allow weak contractions of the tubule.
The germinal epithelium consists of two types of cells:
Large nondividing Sertoli cells, which physically and metabolically support developing sperm cell precursors.
Dividing cells of the spermatogenic lineage.
Spermatogenic Lineage
Cells develop from progenitor cells to fully formed sperm cells over approximately 10 weeks.
Spermatogenesis involves mainly mitosis and meiosis.
Followed by spermiogenesis, the final differentiation process occurring in the haploid male germ cells.
Spermatogenesis
Begins at puberty with proliferation of stem and progenitor cells called spermatogonia.
Small round cells about 12 μm in diameter.
Occupy a basal niche in the epithelial wall of the tubules, next to the basement membrane and closely associated with Sertoli cell surfaces.
Different stages of spermatogonia development can be recognized by subtle changes in shape and staining properties of their nuclei.
Type A spermatogonia:
Dark, ovoid nuclei.
Act as stem cells, dividing infrequently and giving rise both to new stem cells and to cells with more pale-staining, ovoid nuclei that divide more rapidly as transit amplifying (progenitor) cells.
Undergo several unique clonal divisions that leave most of the cells interconnected as a syncytium.
Type B spermatogonia:
More spherical and pale nuclei.
Each undergoes a final mitotic division to produce two cells that grow in size and become primary spermatocytes.
Primary spermatocytes:
Spherical cells with euchromatic nuclei.
Replicate their DNA, so each chromosome consists of duplicate chromatids, and enter meiosis, during which homologous chromosomes come together in synapsis, DNA recombination occurs, and two rapid cell divisions produce haploid cells.
Have 46 (44 + XY) chromosomes, the diploid number, and a DNA content of 4N.
Enter the first meiotic prophase that lasts about 3 weeks.
Largest cells of the spermatogenic lineage and are characterized by the presence of partially condensed chromosomes in various stages of synapsis and recombination.
Secondary spermatocytes:
Homologous chromosomes separate in the first meiotic division, which produces smaller cells called secondary spermatocytes with only 23 chromosomes (22 + X or 22 + Y), but each still consists of two chromatids so the amount of DNA is 2N.
Rare in testis sections because they are very short-lived cells that remain in interphase only briefly and quickly undergo the second meiotic division.
Spermatids:
Division of each secondary spermatocyte separates the chromatids of each chromosome and produces two haploid cells.
Each contains 23 chromosomes.
No S phase (DNA replication) occurs between the first and second meiotic divisions, the amount of DNA per cell is reduced by half when the chromatids separate and the cells formed are haploid (1N).
With fertilization, a haploid ovum and sperm produced by meiosis unite and the normal diploid chromosome number is restored.
The Clonal Nature of Male Germ Cells
Stem cells produced by mitotic divisions of spermatogonia remain as separate cells.
All subsequent divisions of the daughter cells that become transit amplifying progenitor cells have incomplete cytokinesis after telophase, and the cells remain attached to one another by intercellular bridges of cytoplasm.
These allow free cytoplasmic communication among the cells during their remaining mitotic and meiotic divisions.
Clones of approximately a hundred cells may remain linked through meiosis.
The cytoplasmic bridges allow the haploid cells to be supplied with products of the complete diploid genome, including proteins and RNA encoded by genes on the X or Y chromosome missing in their haploid nuclei.
The germ cells finally become separated from one another during differentiation.
The cellular events and changes between the final mitoses of spermatogonia and the formation of spermatids take about 2 months.
Cells at different stages of development are typically grouped together along the tubule, with the intercellular bridges helping to coordinate their divisions and differentiation.
Spermiogenesis
The final phase of sperm production.
The temperature-sensitive process by which spermatids differentiate into spermatozoa, which are highly specialized to deliver male DNA to the ovum.
No cell division occurs during this process, and as with spermatogenesis the cells involved remain associated with Sertoli cells.
Haploid spermatids are small (7-8 μm in diameter) cells near the lumen of the seminiferous tubules.
Includes formation of the acrosome, condensation and elongation of the nucleus, development of the flagellum, and the loss of much of the cytoplasm.
The end result is the mature spermatozoon, which is released from the Sertoli cell surface into the tubule’s lumen.
Commonly divided into four phases:
Golgi phase:
The cytoplasm contains a prominent Golgi apparatus near the nucleus, mitochondria, paired centrioles, and free ribosomes.
Small proacrosomal vesicles from the Golgi apparatus coalesce as a single membrane-limited acrosomal cap close to one end of the nucleus.
The centrioles migrate to a position farthest from the acrosomal cap, and one acts as a basal body, organizing the axoneme of the flagellum which is structurally and functionally similar to that of a cilium.
Cap phase:
The acrosomal cap spreads over about half of the condensing nucleus.
The acrosome is a specialized type of lysosome containing hydrolytic enzymes, mainly hyaluronidase and a trypsin-like protease called acrosin.
These enzymes are released when a spermatozoon encounters an oocyte and the acrosomal membrane fuses with the sperm’s plasma membrane.
They dissociate cells of the corona radiata and digest the zona pellucida, both structures that surround the egg.
This process, the acrosomal reaction, is one of the first steps in fertilization.
Acrosome phase:
The head of the developing sperm, containing the acrosome and the condensing nucleus, remains embedded in the Sertoli cell while the growing axoneme extends into the lumen of the tubule.
Nuclei become more elongated and very highly condensed, with the histones of nucleosomes replaced by small basic peptides called protamines.
Flagellum growth continues as the tail, and mitochondria aggregate around its proximal region to form a thickened middle piece where the ATP for flagellar movements is generated.
Maturation phase:
Unneeded cytoplasm is shed as a residual body from each spermatozoon, and remaining intercellular bridges are lost.
Mature but not yet functional or mobile sperm are released into the lumen of the tubule.
Medical Applications
Decreased semen quality, which is frequently idiopathic (arising from unknown causes), is a major cause of male infertility.
Common features of poor semen quality include oligospermia (ejaculate volume > 2 mL), sperm cell density less than 10-20 million/mL, abnormal sperm morphology, and flagellar defects that impair sperm motility.
Sertoli Cells
Tall “columnar” epithelial cells that nourish the spermatogenic cells and divide the seminiferous tubules into two (basal and adluminal) compartments.
All cells of the spermatogenic lineage are closely associated with the extended surfaces of Sertoli cells and depend on them for metabolic and physical support.
Adhere to the basal lamina, and their apical ends extend to the lumen.
Each Sertoli cell supports 30-50 developing germ cells.
Contain abundant SER, some rough ER, well-developed Golgi complexes, numerous mitochondria, and lysosomes.
Their nuclei are typically ovoid or triangular, euchromatic, and have a prominent nucleolus, features that allow Sertoli cells to be distinguished from the neighboring germ cells.
Important in Sertoli cell function are elaborate tight occluding junctions between their basolateral membranes that form a blood-testis barrier within the seminiferous epithelium.
The tightest blood-tissue barrier in mammals, this physical barrier is one part of a system that prevents autoimmune attacks against the unique spermatogenic cells, which first appear after the immune system is mature and central self-tolerance is well established.
Spermatogonia lie in a basal compartment of the tubule, below the tight junctions and not sealed off from the vascularized interstitial tissue containing lymphocytes and other immune cells.
Newly formed primary spermatocytes temporarily disassemble the adhesion molecules of the local occluding junctions and move into the tubule’s adluminal compartment while still adhering to Sertoli cells.
Adluminal migration occurs without compromising the blood-testis barrier.
Sertoli cells are also connected and coupled ionically by gap junctions, which may help regulate the transient changes in the occluding junctions and synchronize activities in the spermatogenic cells.
As the flagellar tails of the spermatids develop, they appear as tufts extending from the apical ends of the Sertoli cells.
Related to their role in establishing the blood-testis barrier, Sertoli cells have three general functions:
Support, protection, and nutrition of the developing spermatogenic cells:
Because spermatocytes, spermatids, and developing sperm are isolated from plasma proteins and nutrients by the blood-testis barrier, they depend on Sertoli cells for production or transport into the lumen of metabolites and nutritive factors such as the iron-transport protein transferrin.
Thus, while protecting spermatogenic cells from circulating immune components, Sertoli cells supply many plasma factors needed for cell growth and differentiation.
Exocrine and endocrine secretion:
Sertoli cells continuously release into the seminiferous tubules water that carries new sperm out of the testis.
Production of nutrients and androgen-binding protein (ABP), which concentrates testosterone to a level required for spermiogenesis, is promoted by follicle-stimulating hormone (FSH).
As endocrine cells, they secrete the 39-kDa glycoprotein inhibin, which feeds back on the anterior pituitary gland to suppress FSH synthesis and release.
In the fetus, Sertoli cells also secrete a 140-kDa glycoprotein called müllerian-inhibiting substance (MIS) that causes regression of the embryonic müllerian (paramesonephric) ducts; in the absence of MIS, these ducts persist and become parts of the female reproductive tract.
Phagocytosis:
During spermiogenesis, excess cytoplasm shed as residual bodies is phagocytosed and digested by Sertoli cell lysosomes.
No proteins from sperm normally pass back across the blood-testis barrier.
Medical Applications
Acute or chronic inflammation of the testis, orchitis, frequently involves the ducts connecting this organ to the epididymis.
Common forms of orchitis are produced by infective agents and occur secondarily to a urinary tract infection or a sexually transmitted pathogen such as Chlamydia or Neisseria gonorrhoeae entering the testis from the epididymis or via the lymphatics.
Acute epididymitis is a result of sexually transmitted infections such as gonorrhea or Chlamydia infection and causes intrascrotal pain and tenderness.
Persistent inflammation of the epididymis, such as that associated with gonorrhea infections, includes massive invasion by leukocytes into the infected duct, stimulating fibrosis that obstructs the epididymis and is a common cause of male infertility.
Intratesticular Ducts
The straight tubules (or tubuli recti), the rete testis, and the efferent ductules, all of which carry spermatozoa and liquid from the seminiferous tubules to the duct of the epididymis.
The loops of seminiferous tubules join the rete testis by the short straight tubules, which are lined initially only by Sertoli cells.
These empty into the rete testis, an interconnected network of channels lined with cuboidal epithelium and supported by connective tissue of the mediastinum.
The rete testis drains into about 20 efferent ductules lined by an unusual epithelium in which groups of nonciliated cuboidal cells alternate with groups of taller ciliated cells and give the tissue a characteristic scalloped appearance.
The nonciliated cells absorb some of the fluid secreted by the Sertoli cells of seminiferous tubules.
This absorption and the ciliary activity create a fluid flow that carries sperm passively out of the testis toward the epididymis.
A thin layer of circularly oriented smooth muscle cells in the walls of efferent ductules aids the movement of sperm into the duct of the epididymis.
Excretory Genital Ducts
Those of the epididymis, the ductus (or vas) deferens, and the urethra.
They transport sperm from the scrotum to the penis during ejaculation.
Epididymis
Long, coiled duct, surrounded by connective tissue.
Lies in the scrotum along the superior and posterior sides of each testis.
About 4-5 m in length.
Includes a head region where the efferent ductules enter, a body, and a tail opening into the ductus deferens.
Passage of sperm through the duct of the epididymis normally takes 2-4 weeks, during which spermatozoa undergo maturation and acquire the ability to fertilize.
Important changes:
Development of the competence for independent forward motility
Maturation of the acrosome
Biochemical and organizational changes within the cell membrane.
Fluid within the epididymis contains glycolipid “decapacitation factors” that bind the plasma membranes of sperm and block acrosomal reactions and fertilizing ability until these factors are removed as part of the capacitation process in the female reproductive tract.
The epididymal duct is lined with pseudostratified columnar epithelium consisting of columnar principal cells, with characteristic long stereocilia, and small round stem cells.
The principal cells secrete glycolipids and glycoproteins but also absorb most of the remaining water and remove residual bodies or other debris not removed earlier by Sertoli cells.
The duct epithelium is surrounded by a few layers of smooth muscle cells, arranged as inner and outer longitudinal layers as well as a circular layer in the tail of the epididymis.
At ejaculation peristaltic contractions of this muscle move the sperm rapidly along the duct and empty the epididymal tail and distal body regions.
Ductus or Vas Deferens
Long straight tube with a thick, muscular wall and a relatively small lumen.
Continues toward the prostatic urethra where it empties.
Its mucosa is slightly folded longitudinally, the lamina propria contains many elastic fibers, and the epithelial lining is pseudostratified with some cells having sparse stereocilia.
The very thick muscularis consists of longitudinal inner and outer layers and a middle circular layer.
The muscles produce strong peristaltic contractions during ejaculation, which rapidly move sperm along this duct from the epididymis.
Forms part of the spermatic cord, which also includes the testicular artery, the pampiniform plexus, and nerves.
Following the general path along which the embryonic testes descend, each ductus passes over the urinary bladder where it enlarges as an ampulla (L. a small bottle) where the epithelium is thicker and more extensively folded.
Within the prostate gland, the ends of the two ampullae merge with the ducts of the two seminal vesicles, joining these ducts to form the ejaculatory ducts which open into the prostatic urethra.
Medical Applications
Vasectomy: most common surgical method of male contraception.
In this procedure, a very small incision is made through the scrotal skin near the two ducts, and each vas is exposed, cut, and the two ends (or only the end leading to the abdomen) are cauterized and tied.
After vasectomy, sperm are still produced, but they degenerate and are removed by macrophages in the epididymis (and in the scrotal sac if the short portion of the vas is left open-ended.)
Accessory Glands
Produce secretions that are mixed with sperm during ejaculation to produce semen and that are essential for reproduction.
The seminal vesicles (or glands), the prostate gland, and the bulbourethral glands.
Seminal Vesicles
Two seminal vesicles consist of highly tortuous tubes, each about 15-cm long, enclosed by a connective tissue capsule.
The unusual mucosa of the tube displays a great number of thin, complex folds that fill much of the lumen.
The folds are lined with simple or pseudostratified columnar epithelial cells rich in secretory granules.
The lamina propria contains elastic fibers and is surrounded by smooth muscle with inner circular and outer longitudinal layers that empty the gland during ejaculation.
The seminal vesicles are exocrine glands in which production of their viscid, yellowish secretion depends on testosterone.
Fluid from seminal vesicles typically makes up about 70% of the ejaculate and its components include the following:
Fructose, a major energy source for sperm, as well as inositol, citrate, and other metabolites
Prostaglandins, which stimulate activity in the female reproductive tract
Fibrinogen, which allows semen to coagulate after ejaculation.
Prostate Gland
Dense organ that surrounds the urethra below the bladder.
Approximately 2 cm × 3 cm × 4 cm in size and weighs about 20 g.
A collection of 30-50 tubuloacinar glands embedded in a dense fibromuscular stroma in which smooth muscle contracts at ejaculation.
Ducts from individual glands may converge but all empty directly into the prostatic urethra, which runs through the center of the prostate.
The glands are arranged in three major zones around the urethra:
The transition zone occupies only about 5% of the prostate volume, surrounds the superior portion of the urethra, and contains the periurethral mucosal glands.
The central zone comprises 25% of the gland’s tissue and contains the periurethral submucosal glands with longer ducts.
The peripheral zone, with about 70% of the organ’s tissue, contains the prostate’s main glands with still longer ducts.
The tubuloacinar glands are all lined by a simple or pseudostratified columnar epithelium and produce fluid that contains various glycoproteins, enzymes, and small molecules such as prostaglandins and is stored until ejaculation.
A clinically important product of the prostate is prostate-specific antigen (PSA), a 34-kDa serine protease that helps liquefy coagulated semen for the slow release of sperm after ejaculation.
Small amounts of PSA also leak normally into the prostatic vasculature; elevated levels of circulating PSA indicate abnormal glandular mucosa typically due to prostatic carcinoma or inflammation.
Small spherical concretions, 0.2-2 mm in diameter and often partially calcified, are normally present in the lumens of many prostatic tubuloacinar glands.
These concretions, called corpora amylacea, containing primarily deposited glycoproteins and keratan sulfate, may become more numerous with age but seem to have no physiologic or clinical significance.
The prostate is surrounded by a fibroelastic capsule, from which septa extend and divide the gland into indistinct lobes.
Like the seminal vesicles, the prostate’s structure and function depend on the level of testosterone.
Medical Applications
The prostate gland is prone to common problems:
Chronic prostatitis, usually involving bacteria or other infectious agents.
Nodular hyperplasia or benign prostatic hypertrophy, occurring mainly in the periurethral mucosal glands where it often leads to compression of the urethra and problems with urination.
Prostate cancer (adenocarcinoma), the most common cancer in nonsmoking men, occurring mainly in glands of the peripheral zone.
Bulbourethral Glands
The paired round bulbourethral glands (or Cowper glands), 3-5 mm in diameter, are located in the urogenital diaphragm and empty into the proximal part of the penile urethra.
Each gland has several lobules with tubuloacinar secretory units surrounded by smooth muscle cells and lined by a mucus-secreting simple columnar epithelium that is also testosterone-dependent.
During erection, the bulbourethral glands, as well as numerous, very small, and histologically similar urethral glands along the penile urethra, release a clear mucus-like secretion that coats and lubricates the urethra in preparation for the imminent passage of sperm.
Penis
Consists of three cylindrical masses of erectile tissue, plus the penile urethra, surrounded by skin.
Two of the erectile masses—the corpora cavernosa—are dorsal; the ventral corpus spongiosum surrounds the urethra.
At its end, the corpus spongiosum expands, forming the glans.
Most of the penile urethra is lined with pseudostratified columnar epithelium.
In the glans, it becomes stratified squamous epithelium continuous with that of the thin epidermis covering the glans surface.
Small mucus-secreting urethral glands are found along the length of the penile urethra.
In uncircumcised men, the glans is covered by the prepuce or foreskin, a retractable fold of thin skin with sebaceous glands on the internal surface.
The corpora cavernosa are each surrounded by a dense fibroelastic layer, the tunica albuginea.
All three erectile tissues consist of many venous cavernous spaces lined with endothelium and separated by trabeculae with smooth muscle and connective tissue continuous with the surrounding tunic.
Central arteries in the corpora cavernosa branch to form nutritive arterioles and small coiling helicine arteries, which lead to the cavernous vascular spaces of erectile tissue.
Arteriovenous shunts are present between the central arteries and the dorsal veins.
Penile erection involves blood filling the cavernous spaces in the three masses of erectile tissue.
Triggered by external stimuli to the CNS, erection is controlled by autonomic nerves in these vascular walls.
Parasympathetic stimulation relaxes the trabecular smooth muscle and dilates the helicine arteries, allowing increased blood flow and filling the cavernous spaces.
This enlarges the corpora cavernosa and causes them to compress the dorsal veins against the dense tunica albuginea, which blocks the venous outflow and produces tumescence and rigidity in the erectile tissue.
Beginning at ejaculation, sympathetic stimulation constricts the helicine arteries and trabecular muscle, decreasing blood flow into the spaces, lowering the pressure there, and allowing the veins to drain most blood from the erectile tissue.
Medical Applications
At the beginning of an erection, acetylcholine from parasympathetic nerves causes the vascular endothelial cells of the helicine arteries and cavernous tissue to release nitric oxide (NO).
NO diffuses into the surrounding smooth muscle cells and activates guanylate cyclase to produce cyclic GMP, which causes these cells to relax and promotes blood flow for the erection.
Erectile dysfunction, or impotence, can result from diabetes, anxiety, vascular disease, or nerve damage during prostatectomy.
The drug sildenafil may alleviate the problem by inhibiting the phosphodiesterase that degrades cyclic GMP in the smooth muscle cells of helicine arteries and erectile tissue.
The subsequent higher level of cGMP promotes relaxation of these cells and enhances the neural effect to produce or maintain an erection.