Male Reproductive System & Sperm Production

Male Reproductive System

• Consists of the gonads (testes) and accessory sex organs composed of glands and ducts.
• Septa from the capsule divide each testis into approximately 250 incomplete lobules.
• Septa converge toward the midline of the posterior border, forming the mediastinum testis, a thickening of the tunica albuginea.
• Each lobule contains 1-4 seminiferous tubules in a connective tissue stroma.

Seminiferous Tubules & Sperm Production

• Testes contain up to 900 coiled seminiferous tubules, the site of sperm formation.
• Septa divide the testis into lobules which contain the seminiferous tubules.
• Sperm formation is supported by Sertoli and Leydig cells.

Leydig Cells and Testosterone

• Leydig cells, or interstitial cells, are located between the seminiferous tubules.
• These cells contain cholesterol-lipid droplets and secrete testosterone in response to luteinizing hormone.
• LH stimulates Leydig cells to produce testosterone at puberty.
• Testosterone promotes creation of spermatozoa, secretion from sex glands, and male secondary sex characteristics.

Sertoli Cells and the Blood-Testis Barrier

• Sertoli cells rest on a basal membrane and directly contact one another and germ cells.
• Sertoli cells are connected via tight junctions, dividing the tubules into two compartments: basal and adluminal.
• Tight junctions between Sertoli cells form the blood-testis barrier, which restricts diffusion of substances from the interstitium and blood vessels.
• Inter-Sertoli cell junctions remodel to allow germ cell movement while maintaining barrier function.

Compartmentalization of Spermatogenesis

• Mitotic spermatogonia are located in the basal compartment.
• Differentiating progeny enter the adluminal compartment, sealed off from the basal compartment.
• The Sertoli cell controls the environment in the adluminal compartment where meiosis and spermatid differentiation occur.
• The basal compartment contains spermatogonia with doubled DNA prior to meiosis.
• The adluminal compartment contains spermatocytes, spermatids, and spermatozoa.
• The blood-testis barrier prevents spermatozoa from entering the blood circulation, which is important because it stops the immune system from producing antibodies against monoploid spermatozoa antigens, preventing autoimmune orchitis and sterility.

Sperm Transport

• Sperm are transported in the following order: seminiferous tubules, epididymis, and lastly the vas deferens.
• Sperm fully transforms in the epididymis before entering the vas deferens.
• The vas deferens enlarges into the ampulla before entering the prostate gland.
• The ampulla and seminal vesicles contents enter the ejaculatory ducts.
• The ejaculatory ducts lead through the prostate gland and empty into the internal urethra.
• Prostatic ducts empty from the prostate gland into the ejaculatory duct and into the prostatic urethra.
• Urethra connects the testis to the exterior of the body.
• The urethra contains alkaline mucus pre-ejaculate from urethral and bulbourethral glands that neutralizes acidic urinary pH.

Penile Physiology

• Cavernous smooth musculature and arteriolar smooth muscles are key in the erectile process.
• In a flaccid state, these muscles are tonically contracted with limited arterial flow and a blood partial pressure of oxygen (PO2) of about 35mmHg.
• The flaccid penis remains in moderate contraction.

Puberty Onset

• During childhood, the hypothalamus does not secrete significant amounts of GnRH due to inhibition by sex steroid hormones.
• Puberty begins with increased GnRH secretion.
• Nutritional deprivation delays puberty, and impacts reproductive neuroendocrine function.
• Kisspeptin expression increases during puberty in the infundibular nucleus of the medium basal hypothalamus (MBH) in both sexes.
• Pubertal increases in kisspeptin correlate with changes in GnRH pulses.
• Specific genes regulate kisspeptin synthesis, inhibiting it in childhood and inducing it after puberty.

Spermatogenesis

• Primordial germ cells migrate to the testes, becoming spermatogonia.
• Spermatogonia undergo mitosis, proliferation, and differentiation to form sperm during puberty.
• Spermatogenesis occurs in the seminiferous tubules, stimulated by anterior pituitary gonadotropic hormones, beginning around age 13 and continuing throughout life.
• Spermatogonia migrate among Sertoli cells toward the central lumen of the seminiferous tubule in the first stage.

Sperm Formation and Structure

• Primordial germ cells of the fetus transform into spermatids in the adult male.
• Spermatids differentiate into spermatozoa, elongating to form a head and tail.
• The sperm head contains the nucleus surrounded by a thin cytoplasmic and cell membrane layer.
• The acrosome, formed mainly from the Golgi apparatus, covers the anterior two-thirds of the head.
• Acrosome contains hyaluronidase and proteolytic enzymes to penetrate and fertilize the ovum.

Meiosis in Sperm Development

• Spermatogonia cross into the Sertoli cell layer, modifying and enlarging into primary spermatocytes.
• Each primary spermatocyte undergoes meiosis, dividing to form two secondary spermatocytes.
• Secondary spermatocytes divide to form spermatids which eventually transform into spermatozoa (sperm).

Sperm Chromosomes

• Spermatocytes initially contain 46 chromosomes (23 pairs), but each spermatid receives 23 chromosomes.
• Spermatids contain half of the father's genetic traits and half of the genes provided by the mother.

Duration of Spermatogenesis

• The complete process from spermatogonia to spermatozoa takes 74 days.

Sperm Tail or Flagellum Structure

• Composed of a central skeleton of 11 microtubules called the axoneme.
• Contains a thin cell membrane.
• Contains mitochondria surrounding axoneme in the proximal portion of the tail.

Sperm Motility

• Results from flagellar movement due to the longitudinal sliding motion between the anterior and posterior tubules of the axoneme.

Sperm Maturation in the Epididymis

• Sperm formed in the seminiferous tubules are transported to the 6-meter-long epididymis, where they mature.
• Initially, sperm in the seminiferous tubules and epididymis are nonmotile and infertile.
• After 18-24 hours, sperm develop the capability of motility, despite inhibitory proteins in epididymal fluid.

Sperm Storage

• Adult testes can produce approximately 120 million sperm daily.
• Most sperm are stored in the vas deferens, remaining fertile for about a month.
• They are kept inactive by inhibitory substances from duct secretions.
• High sexual activity can deplete sperm storage more quickly.

Sperm Activation

• After ejaculation, sperm become motile and capable of fertilizing the ovum, which is called maturation.
• Sertoli cells and the epididymis secrete a nutrient-rich fluid containing testosterone, estrogens, hormones, enzymes, and nutrients essential for maturation that is ejaculated with the sperm.

Sex Chromosome Determination

• Each spermatogonium contains either one X chromosome or one Y chromosome, but not both.
• Meiotic division results in a Y chromosome going to one spermatid and an X chromosome to another.
• The sex of the offspring depends on the type of sperm (X or Y) that fertilizes the ovum.

Hormonal Influence on Sperm Growth

• Testosterone produced by Leydig cells in the interstitium is vital for growth and division of testicular germinal cells.

Hormonal Control of Testicular Function

• LH from the anterior pituitary stimulates testosterone secretion by Leydig cells.
• FSH from the anterior pituitary controls Sertoli cell functions and induces spermiogenesis.

Sertoli Cell Products

• Sertoli cells produce approximately 60 proteins related to reproduction, including inhibin, androgen-binding protein (ABP), and anti-müllerian hormone.

Androgen-Binding Protein

• ABP is a glycoprotein with high affinity for testosterone and dihydrotestosterone.
• FSH and testosterone stimulate ABP release.

Effects of ABP on Androgens

• When ABP binds testosterone or dihydrotestosterone, these hormones become less lipophilic, increasing their concentration in the seminiferous tubule lumen.

Seminiferous Tubule Regulation

• When sperm production is inadequate, FSH secretion increases.
• Excessive spermatogenesis causes FSH secretion to decrease.

Role of Inhibin

• Sertoli cells produce inhibin, a hormone that inhibits FSH secretion and possibly GnRH secretion.
• Inhibin is a glycoprotein (10-30 kD) isolated from cultured Sertoli cells.
• It has a potent inhibitory effect on the anterior pituitary gland and provides negative feedback for spermatogenesis control, and provides a mechanism for regulating testosterone secretion.

Hormonal Factors

• Inhibin, in concert with testosterone, is a glycoprotein that inhibits FSH secretion.
• Low concentrations of estrogen induces spermiogenesis, but high concentrations causes infertility due to the effect in Sertoli cells..
• Growth hormone and thyroid hormones regulate testicular metabolic functions.
• Growth hormone promotes early spermatogonia division; its absence causes severe spermatogenesis deficiency and infertility.

Mature Sperm Physiology

• Mature, motile, and fertile sperm released by ejaculation move through fluid at 1 to 4 mm/min.
• Sperm motility is enhanced in a slightly alkaline medium but depressed in an acidic medium.
• Activity of sperm increases with increasing temperature, but high temperatures can shorten sperm life.
• Sperm viability lasts for weeks in testes but only 1-2 days in the female genital tract.

Seminal Vesicle Function

• Seminal vesicles contain secretory epithelium and secrete a mucoid material containing fructose, citric acid, nutrients, prostaglandins, and fibrinogen.
• During ejaculation, each seminal vesicle empties its contents into the ejaculatory duct after the vas deferens empties.
• This provides nutrients until sperm fertilizes the ovum.
• Prostaglandins affect sperm motility and cervical mucus receptivity.
• Triggers uterus and fallopian tube contractions to draw sperm toward ovaries.

Prostatic Gland Function

• The prostate gland secretes a fluid containing calcium, citrate, phosphate ions, a clotting enzyme, and profibrinolysin that is facilitated by capsular contraction.
• Prostatic fluid is alkaline, neutralizing the acidity of the vas deferens, which is rich in citric acid and metabolic byproducts of sperm aiding in fertilization.
• Vaginal secretions are acidic (pH 3.5-4.0) to prevent infection.
• Slightly alkaline prostatic fluid neutralizes acidic seminal fluids and enhances motility/fertility of sperm.
• Optimal sperm motility occurs at pH 6.0-6.5.

Semen Composition

• Composed of fluid and sperm from the vas deferens (10%), seminal vesicles (60%), and prostate gland (30%).
• Also contains small amounts of fluid from mucous/bulbourethral glands.
• Bulky Seminal vesicle fluid washes sperm through the ejaculatory ducts.

Hormonal Regulation

• Testosterone inhibits anterior pituitary secretion of LH by decreasing GnRH secretion, thus decreasing both LH and FSH secretion.
• Testosterone levels are automatically regulated.

Spermatogenesis Regulation

• FSH binds to Sertoli cells in seminiferous tubules and stimulates growth and secretion of spermatogenic substances.
• Testosterone and dihydrotestosterone diffuse into seminiferous tubules from Leydig cells, influencing spermatogenesis.
• Both FSH and testosterone are necessary to begin spermatogenesis.