Male Reproductive System

Introduction

The male reproductive system is specialized for lifelong sperm production beginning at puberty. Sertoli cells nourish developing germ cells and form the blood-testis barrier, while Leydig cells produce testosterone, the hormone essential for spermatogenesis and reproductive function.

• The primary function of the male reproductive system is to produce viable sperm capable of fertilizing the ovum.
• A distinctive feature is continuous spermatogenesis after puberty, with millions of sperm produced daily under normal conditions.

Functional Anatomy

• The male reproductive system includes the testes, epididymis, vas deferens, ejaculatory ducts, prostate, urethra, and penis.
• Its two major functions are spermatogenesis and testosterone production.
• Sperm are formed in the testes and then pass into the epididymis for maturation.
• The epididymis and proximal vas deferens act as storage sites for sperm.
• During ejaculation, sperm travel through the ejaculatory ducts into the urethra and exit through the penis.

The Testes

• The testes are the primary male reproductive glands and are located within the scrotum.
• Their main functions are sperm production and secretion of testosterone.
• During fetal life, the testes develop in the posterior abdominal cavity near the kidneys.
• They normally descend through the inguinal canal into the scrotum during late pregnancy.
• Failure of descent is called cryptorchidism and may impair fertility if untreated.

Why the Scrotum Is Cooler

• Normal sperm production requires a temperature about 2–4°C below core body temperature.
• The scrotum provides this cooler environment essential for spermatogenesis.

Factors Maintaining Lower Temperature

• External location: The scrotum hangs outside the abdominal cavity, reducing heat exposure from internal organs.
• Pampiniform plexus: This venous network surrounds the testicular artery and acts as a countercurrent heat exchanger.
• Cooler venous blood absorbs heat from incoming arterial blood before it reaches the testis.

Role of Muscles

• The cremaster muscle is skeletal muscle present in the spermatic cord.
• It contracts during cold exposure, raising the testes closer to the body for warmth.
• It relaxes in warm conditions, allowing the testes to descend and cool.
• The dartos muscle is smooth muscle in the scrotal wall.
• It contracts in cold weather, causing wrinkling of scrotal skin and reducing heat loss.
• In warmth, it relaxes, making the scrotal skin smoother.

Clinical Importance

• These temperature-control mechanisms help preserve normal fertility and protect against temporary heat-related reduction in sperm production.

Size and Blood Supply

• Each adult testis weighs about 10–15 grams.
• Average length is about 5 centimeters, and width is about 2.5 centimeters.
• Blood supply is through the testicular arteries, which arise directly from the abdominal aorta.

Functional Histology of Testis

• Each testis is enclosed by a dense fibrous capsule called the tunica albuginea.
• Septa extending from this capsule divide the testis into multiple lobules.
• Each lobule contains tightly coiled seminiferous tubules, the site of sperm formation.
• Seminiferous tubules are long, narrow channels measuring about 50 centimeters in length and 250 micrometers in diameter when uncoiled.
• Tubules continue as straight tubules that drain into the rete testis and then into the epididymis.
• Myoid cells surround the tubules and help propel tubular fluid and sperm.
• The interstitial tissue contains Leydig cells, capillaries, connective tissue, and fibroblasts.
• Leydig cells synthesize testosterone.

Seminiferous Tubule

• Each seminiferous tubule is bounded by a basement membrane separating it from interstitial tissue.
• Outside the membrane are Leydig cells, myoid cells, and connective tissue.
• Beneath the membrane lie spermatogonia and Sertoli cells.
• Two major cell groups are present: germ cells and supporting Sertoli cells.

Sertoli Cells

Sertoli cells are supporting cells of the seminiferous tubules and form much of the tubular epithelium.

Structure of Sertoli cells

• They are tall, irregular cells extending from the basement membrane to the lumen.
• Developing sperm cells remain closely associated with the apical surface of Sertoli cells during maturation.
• Adjacent Sertoli cells are joined by tight junctions near their basal region.
• These junctions divide the tubule into basal and adluminal compartments.

Basal Compartment

• The basal compartment lies near the basement membrane.
• It mainly contains spermatogonia and early primary spermatocytes.
• This region is relatively accessible to substances from nearby capillaries.

Adluminal Compartment

• The adluminal compartment lies toward the lumen.
• It contains later-stage spermatocytes, spermatids, and maturing sperm cells.
• Tight junctions help protect these developing cells from harmful blood-borne substances.

Blood-Testis Barrier

• The blood-testis barrier is formed mainly by tight junctions between adjacent Sertoli cells near the basement membrane.
• These junctions greatly restrict movement of many substances from blood and interstitial fluid into the adluminal compartment.
• Lipid-soluble hormones such as steroids and selected proteins may cross more easily.
• The barrier protects developing germ cells from toxins, pathogens, and immune recognition.
• It helps maintain a specialized microenvironment required for normal spermatogenesis.
• Large molecules are largely prevented from entering the inner tubular compartment.
• Developing spermatocytes must move from the basal region to the adluminal region during maturation.
• This occurs through coordinated remodeling of Sertoli cell junctions.
• New junctions form behind migrating cells while older junctions open ahead of them.
• Therefore, germ cells pass forward without permanent disruption of the barrier.

H6: Functions of BTB:

• The blood-testis barrier protects developing germ cells from harmful blood-borne substances and infectious agents.
• It prevents sperm-related antigens from entering circulation, thereby reducing the risk of autoimmune reactions.
• This protection is important because germ cells develop after immune tolerance is established.
• The barrier regulates the composition of seminiferous tubular fluid.
• Tubular fluid contains relatively low levels of proteins and glucose compared with plasma.
• It is enriched with androgens, potassium ions, inositol, and selected amino acids needed for spermatogenesis.
• The barrier also helps maintain appropriate osmolality, supporting fluid movement into the tubular lumen.

Functions of Sertoli Cells

• Sertoli cells are the principal supporting cells of the seminiferous tubules and are essential for normal sperm production.
• They provide structural support to developing germ cells throughout spermatogenesis.
• These cells supply nutrients, growth factors, and metabolic substrates required for maturation of germ cells.
• Their cytoplasm is rich in proteins and secretory organelles that assist cellular development.

Support of Germ Cells

• Sertoli cells anchor developing spermatogenic cells and organize them within the seminiferous epithelium.
• Several spermatids may remain attached to one Sertoli cell during maturation.
• They produce transferrin, an iron-transport protein important for germ cell growth and differentiation.

Phagocytic Function

• Sertoli cells remove damaged germ cells and degenerating cellular material.
• They phagocytose residual bodies, which are excess cytoplasmic fragments shed during transformation of spermatids into spermatozoa.
• This cleaning action maintains a healthy tubular environment.

Tubular Fluid Secretion

• Sertoli cells secrete fluid into the lumen of seminiferous tubules.
• This fluid helps transport sperm toward the rete testis and epididymis.
• It also contributes to the composition of seminal plasma indirectly.

Role in Spermiation

• Spermiation is the release of mature spermatozoa from Sertoli cells into the tubular lumen.
• Sertoli cells aid this process by producing plasminogen activator, which generates plasmin and assists detachment of sperm cells.

Hormonal Responsiveness

• Sertoli cells contain receptors for follicle-stimulating hormone and testosterone.
• Follicle-stimulating hormone acts mainly through cyclic adenosine monophosphate signaling.
• During puberty, sensitivity to these hormones increases, promoting spermatogenesis.

Endocrine Functions

• Sertoli cells secrete several regulatory substances.
• Inhibin suppresses pituitary release of follicle-stimulating hormone.
• Activin enhances follicle-stimulating hormone secretion.
• Follistatin binds activin and reduces its effect.
• Fetal Sertoli cells secrete anti-Müllerian hormone, causing regression of Müllerian ducts in male embryos.
• Sertoli cells also contain aromatase, which converts androgens into estrogens.

Androgen-Binding Protein

• Sertoli cells synthesize androgen-binding protein, which binds testosterone and dihydrotestosterone in tubular fluid.
• This maintains a high local androgen concentration required for sperm production and maturation.
• It also assists movement of androgens toward the epididymis.

Blood-Testis Barrier

• Tight junctions between Sertoli cells form the blood-testis barrier.
• This barrier protects developing germ cells from toxins, pathogens, and immune attack.
• It also helps maintain the specialized chemical environment needed for spermatogenesis.

Germ Cells

• Germ cells are the reproductive epithelial cells of seminiferous tubules.
• Spermatogonia divide and mature into spermatocytes, spermatids, and finally spermatozoa through spermatogenesis.

Leydig Cells

• Leydig cells are the principal steroid-producing cells of the testes.
• Their main product is testosterone, the key androgen required for male reproductive function.

Location

• Leydig cells lie in the interstitial tissue between seminiferous tubules.
• They are located close to capillaries, allowing rapid hormone release into blood.

Structure

These cells contain abundant smooth endoplasmic reticulum and mitochondria, which are essential for steroid synthesis.

Functions

• Testosterone is the major hormone secreted by Leydig cells.
• Smaller amounts of androstenedione and dehydroepiandrosterone may also be produced.

Leydig Cells Activity in Different Phases of Life

• During 8–15 weeks of fetal life, Leydig cells are highly active.
• Fetal testosterone is necessary for development of male internal and external genital structures.
• At this stage, stimulation is mainly by human chorionic gonadotropin rather than luteinizing hormone.
• Activity declines later in fetal life.
• A temporary rise in Leydig cell activity occurs during the first few months after birth, often called mini-puberty.
• Testosterone levels then fall and remain low during childhood.
• At puberty, Leydig cell activity increases markedly under pituitary stimulation.
• After puberty, secretion gradually declines with aging but usually persists throughout adult life.

Regulation of Leydig Cell Activity

• Leydig cells possess receptors for luteinizing hormone.
• Luteinizing hormone stimulates testosterone synthesis through a cyclic adenosine monophosphate pathway.
• Leydig cells do not have functional receptors for follicle-stimulating hormone.
• However, follicle-stimulating hormone acts indirectly through Sertoli cell growth factors that support Leydig cell function.
• Excess estrogen may suppress Leydig cell activity, while normal androgen signaling supports it.

Interaction of Leydig cells with Sertoli cells

• Testosterone diffuses from Leydig cells into nearby seminiferous tubules.
• Sertoli cells bind testosterone using androgen-binding protein, maintaining high local concentrations.
• This testosterone is essential for spermatogenesis.
• It also supports Sertoli cell function and local estrogen formation through aromatization.
• Estrogen produced in Sertoli cells may influence Leydig cell regulation locally.

Functions of Testis

• The testes perform three major roles:
• Spermatogenesis, which is production of sperm cells.
• Steroidogenesis, mainly synthesis of testosterone, later converted to dihydrotestosterone or estradiol in target tissues.
• Secretion of regulatory factors such as inhibin, activin, and follistatin, which influence reproductive physiology.

Epididymis

Seminiferous tubules drain into the rete testis, which connects to the epididymis through efferent ductules.

Structure

• The epididymis lies along the posterior surface of the testis.
• It contains a highly coiled duct about 5 meters long.
• It has three parts: head, body, and tail.

Function

• The epididymis is the main site for sperm storage and post-testicular maturation.
• About 99% of testicular fluid is reabsorbed in the rete testis and epididymis, concentrating sperm cells.
• Sperm entering from the testis are initially non-motile or poorly motile.
• During epididymal transit, sperm gain progressive motility.
• They also acquire the ability to bind the zona pellucida and fertilize the ovum.
• Therefore, sperm from the testis are immature, whereas epididymal sperm are fertile.

Vas Deferens

• The vas deferens receives sperm from the epididymis and transports them toward the ejaculatory duct.
• Its proximal segment can temporarily store sperm.
• It joins the duct of the seminal vesicle to form the ejaculatory duct.
• Sperm may show intrinsic motility, but forward movement mainly depends on peristaltic contractions of the thick muscular wall.
• These contractions become stronger during ejaculation, rapidly propelling sperm into the urethra.

Seminal Vesicle

• The paired seminal vesicles lie posterior to the urinary bladder and near the prostate gland.
• They secrete a viscous, alkaline fluid that forms about 60–70% of semen volume.
• Remaining semen volume mainly comes from the prostate, testes, epididymis, and other accessory glands.
• Their secretion contains fructose, which supplies energy for sperm motility.
• It also contains ascorbate, proteins, and yellow pigments such as flavins.
• Seminal vesicles are a major source of prostaglandins in semen.

Accessory Sex Glands

• The main accessory male sex glands are the prostate gland and bulbourethral glands.

The Prostate Gland

• The ejaculatory ducts open into the prostatic urethra after passing through the prostate.
• The prostate contains numerous branched tubuloalveolar glands.
• Its secretion contributes to semen and contains enzymes such as fibrinolysin and proteolytic factors that help liquefy semen after ejaculation.
• Prostatic fluid also contains acid phosphatase, citrate, and zinc.
• These secretions help maintain sperm motility and reduce sperm clumping.

Bulbourethral Glands

• These glands secrete mucus and alkaline fluid.
• Their secretion lubricates the urethra and helps neutralize residual acidity.

Spermatogenesis

Definition and Course

• Spermatogenesis is the process by which male germ cells develop into mature spermatozoa.
• Primordial germ cells migrate to the developing gonads during embryonic life.
• These cells later differentiate into spermatogonia.
• Spermatogonia lie on the basement membrane of seminiferous tubules.
• During childhood, germ cells remain relatively inactive.
• At puberty, rising gonadotropins and testosterone stimulate initiation of sperm production.
• Spermatogonia divide by mitosis to replenish stem cells and form cells that enter maturation.
• These cells become spermatocytes, spermatids, and finally spermatozoa.
• Spermatogenesis usually continues throughout adult life, though efficiency declines with aging.

Steps of Spermatogenesis

• Spermatogenesis occurs in three major phases: mitosis, meiosis, and spermiogenesis.
• It converts primitive germ cells into mature spermatozoa within seminiferous tubules.

Mitosis

• Spermatogonia located on the basement membrane divide repeatedly by mitosis.
• This stage is called spermatocytogenesis.
• Mitotic division maintains the stem cell population and produces cells for further maturation.
• Two functional groups are formed: type A and type B spermatogonia.
• Type A spermatogonia act as reserve stem cells and continue self-renewal.
• Type B spermatogonia differentiate and move toward the adluminal compartment.
• They enlarge to form primary spermatocytes.

Meiosis

• Primary spermatocytes undergo meiosis I, which reduces chromosome number.
• This produces two secondary spermatocytes that are haploid in chromosome number.
• Secondary spermatocytes rapidly undergo meiosis II.
• Meiosis II forms four spermatids from each primary spermatocyte.
• Each spermatid contains 23 chromosomes: 22 autosomes and one sex chromosome.
• Approximately half carry an X chromosome and half carry a Y chromosome.
• Meiosis also creates genetic variation through recombination and independent assortment.

Spermiogenesis

• Spermiogenesis is the transformation of spermatids into mature spermatozoa.
• It is a differentiation process without further cell division.
• Early spermatids are small, round, and non-motile cells.
• Excess cytoplasm is removed as residual bodies, making the cell lighter and streamlined.
• The nucleus condenses and elongates to form the sperm head.
• Dense nuclear packing helps protect genetic material.
• An acrosomal cap develops over the anterior head.
• The acrosome contains enzymes needed to penetrate the coverings of the ovum.
• A midpiece forms and becomes packed with mitochondria to generate energy.
• A tail (flagellum) develops to produce movement.
• These changes enable efficient progressive motility through the female reproductive tract.
• The streamlined shape improves forward movement.
• Acrosomal enzymes assist fertilization.
• Mature sperm are better adapted to survive variable environments, including acidic vaginal conditions.

Spermiation

• After maturation, sperm remain attached to the apical surface of Sertoli cells.
• Spermiation is the release of mature spermatozoa into the lumen of seminiferous tubules.
• Released sperm then pass toward the epididymis for further maturation.

Capacitation

• Capacitation is a functional maturation process that sperm undergo in the female reproductive tract after ejaculation.
• It increases motility and prepares sperm for the acrosome reaction.
• Capacitation is usually necessary for normal in vivo fertilization.

Structure of Spermatozoa

• A mature spermatozoon is a highly specialized motile cell designed to deliver paternal DNA for fertilization.
• It consists of three main parts: head, midpiece, and tail.
• Human sperm measure about 50–65 micrometers in length and are microscopic in size.

Head

• The head contains a densely packed haploid nucleus with condensed chromatin.
• This compact structure protects genetic material during transport.
• Covering the anterior part of the head is the acrosome, derived from the Golgi apparatus.
• The acrosome contains enzymes such as acrosin, hyaluronidase, neuraminidase, and esterases.
• During fertilization, these enzymes help sperm penetrate the layers surrounding the ovum.
• After sperm entry into the ovum, the nucleus decondenses to form the male pronucleus.

Middle Piece

• The midpiece connects the head to the tail.
• It contains numerous mitochondria arranged in a spiral sheath.
• These mitochondria generate adenosine triphosphate required for sperm movement.
• At its center lies the axial filament formed by microtubules.
• This filament continues into the tail as the axoneme.

Tail Piece

• The tail is responsible for propulsion and is divided into a principal piece and end piece.
• It contains a central axoneme with the classic 9 + 2 microtubule arrangement, seen in cilia and flagella.
• Nine peripheral microtubule doublets surround one central pair.
• Rhythmic bending movements of the tail propel sperm forward.
• Motion is produced by interactions between microtubules and dynein motor proteins using adenosine triphosphate.
• The axoneme is surrounded by a fibrous sheath that adds strength and flexibility.
• The plasma membrane of the tail contains proteins important for motility and fertilization.

Role of CatSper protein:

• The principal piece contains CatSper, a sperm-specific calcium channel.
• Calcium entry through CatSper enhances tail beating and hyperactivated motility, which is important for fertilization.
• The head carries genetic material, the midpiece supplies energy, and the tail provides movement.
• Efficient structure and motility are essential for natural conception.

Duration of Spermatogenesis

• In humans, development of a sperm cell from a spermatogonium usually takes about 64–74 days.
• This sequence of cellular changes is often called the spermatogenic cycle.
• Approximate durations of stages are relatively constant:
• Spermatogonia to primary spermatocytes: 16–20 days.
• Primary spermatocytes through meiosis I: 23–25 days.
• Secondary spermatocytes through meiosis II: about 1 day.
• Spermatids to mature spermatozoa during spermiogenesis: about 24–25 days.
• Hormones such as gonadotropins and testosterone mainly influence the number of sperm produced rather than total cycle duration.
• New waves of spermatogenesis begin every few weeks before earlier waves finish.
• Therefore, seminiferous tubules contain germ cells at multiple stages simultaneously.
• This arrangement ensures a continuous supply of sperm throughout reproductive life.

Rate of Production of Sperms

• One spermatogonial lineage can theoretically generate many spermatids through repeated mitotic and meiotic divisions.
• Adult testes together produce roughly 100–200 million sperm daily under healthy conditions.
• Production per gram of testicular tissue is approximately 6–7 million sperm per day.
• Daily output varies with age, endocrine status, temperature, illness, and lifestyle factors.
• Sperm production gradually declines with aging.
• After about 50 years, production may decrease because of reduced germ cell efficiency and hormonal changes.
• Despite decline, many men retain measurable spermatogenesis into advanced age, sometimes beyond 80–90 years.

Differences between Spermatogenesis and Oogenesis

• In females, most mitotic proliferation of germ cells occurs before birth.
• In males, spermatogonia remain dormant until puberty and then continue dividing during adult life.
• One primary oocyte ultimately yields one mature ovum and polar bodies.
• One primary spermatocyte yields four functional spermatozoa.
• In females, meiosis II is completed only after fertilization.
• In males, meiosis II is completed within the testes during spermatogenesis.
• Female gamete production is cyclic and finite, whereas male gamete production is relatively continuous.

Factors Controlling Spermatogenesis

• Control of spermatogenesis depends mainly on hormonal and environmental influences.
• Proper temperature, nutrition, and intact testicular structure are also necessary.

Hormonal Factors

Androgens

• Testosterone is essential for normal sperm production.
• Luteinizing hormone stimulates Leydig cells to secrete testosterone.
• This creates a high local testosterone concentration within the testes.
• Testosterone diffuses into seminiferous tubules and acts mainly through Sertoli cells, which contain androgen receptors.
• Sertoli cells produce androgen-binding protein, helping maintain high intratubular testosterone levels.
• Testosterone is especially important for later stages of maturation, particularly spermiogenesis.

Follicle-Stimulating Hormone

• Follicle-stimulating hormone acts on Sertoli cells.
• It supports nourishment of germ cells, synthesis of androgen-binding protein, and secretion of growth factors.
• It is particularly important for initiation of spermatogenesis at puberty.
• Together with testosterone, it sustains ongoing sperm production in adults.

Luteinizing Hormone

• Luteinizing hormone indirectly supports spermatogenesis by stimulating Leydig cell testosterone secretion.
• Without adequate luteinizing hormone, intratesticular testosterone falls and sperm production declines.

Estrogen

• Small amounts of estrogen are present in the male reproductive tract.
• Estrogen receptors are found in the rete testis and efferent ducts.
• Estrogen helps fluid reabsorption, concentrating sperm before epididymal maturation.
• Impaired fluid reabsorption may dilute sperm and reduce fertility.

Environmental Factors

• Temperature is a major environmental regulator of spermatogenesis.
• Optimal sperm production occurs when testes remain cooler than body temperature, usually around 34–35°C.
• Excess heat can reduce sperm count and motility.
• Repeated hot baths, tight or insulating scrotal wear, and fever may impair sperm production.
• Very low temperatures can also inhibit normal spermatogenesis.

Semen Analysis

• Semen analysis is a basic investigation used to assess male fertility potential.
• It helps determine whether infertility may be related to sperm production, transport, or accessory gland function.
• It is also used after vasectomy to confirm absence of sperm.
• The sample is usually collected after 2–7 days of sexual abstinence for standard evaluation.
• Fresh semen is examined macroscopically and microscopically.

Composition of Normal Semen

• Volume: usually about 1.5–6 milliliters.
• Color: gray-white or opalescent.
• pH: mildly alkaline, generally 7.2 or higher.
• Liquefaction: semen should liquefy within 15–60 minutes after ejaculation.
• Sperm concentration: commonly 15 million/mL or more.
• Total sperm number: often 39 million or more per ejaculate.
• Motility: a substantial proportion should show progressive movement.
  • Semen contains sperm cells suspended in secretions from accessory glands.
  • Seminal vesicles contribute most of the volume, commonly about 60–70%.
  • Their fluid contains fructose, which provides energy for sperm.
  • They also add prostaglandins and other nutrients.
  • The prostate gland contributes roughly 20–30% of semen volume.
  • Prostatic fluid contains citrate, zinc, enzymes, and prostate-specific antigen, which helps liquefaction and sperm motility.
  • Small contributions come from testes, epididymis, and bulbourethral glands.
  • Bicarbonate and phosphate act as buffers, helping neutralize acidity in the female reproductive tract.
  • Low count, poor motility, abnormal morphology, low volume, or abnormal pH may indicate pathology.
  • Fever, hormonal disorders, obstruction, infection, smoking, alcohol misuse, heat exposure, and medications can affect results.
  • Because semen quality varies, abnormal findings are usually confirmed with repeat testing.

Abnormalities

Volume

• Low semen volume may suggest obstruction, ejaculatory dysfunction, hypogonadism, dehydration, or inflammation of the genital tract.
• Semen volume may gradually decrease with advancing age.

Motility

• Normal fertility requires an adequate proportion of sperm with progressive motility.
• Poor motility reduces the ability of sperm to reach and fertilize the ovum.
• Markedly reduced motility is termed asthenozoospermia and is associated with infertility.
• Causes include infection, varicocele, heat exposure, toxins, and structural tail defects.

Count

• Low sperm concentration is called oligozoospermia.
• Very low counts or absence of sperm can markedly reduce fertility potential.
• Causes include hormonal disorders, testicular failure, genetic disease, or duct obstruction.

Liquefaction

• Semen normally liquefies within about 15–60 minutes after ejaculation.
• Delayed liquefaction may indicate prostatic dysfunction, infection, or abnormal seminal enzymes.
• Persistent thick semen can impair sperm movement.

Morphology

• Abnormal sperm shape is called teratozoospermia.
• Defects may involve the head, midpiece, or tail.
• Examples include double heads, tapered heads, bent necks, coiled tails, or short tails.
• Severe morphological abnormalities may reduce fertilization capacity.

pH

• Normal semen is mildly alkaline.
• Low pH may suggest absent or blocked seminal vesicles or ejaculatory duct obstruction.
• Excess acidity may reduce sperm survival.

Fructose Content

• Fructose is produced mainly by seminal vesicles and provides energy for sperm.
• Low or absent fructose may indicate seminal vesicle dysfunction, ejaculatory duct obstruction, or congenital absence of these structures.

Effects of Vasectomy

• Vasectomy is bilateral interruption or ligation of the vas deferens for permanent male contraception.
• It is generally a safe, effective, and convenient procedure.
• Sperm production and testosterone secretion usually continue normally after vasectomy.
• Some men develop anti-sperm antibodies because sperm remain isolated from the ejaculatory pathway.
• Reversal by vasovasostomy can be technically difficult.
• Fertility after reversal may be reduced by obstruction or anti-sperm antibodies.

Testicular Hormones

Testosterone

• Testosterone is the principal androgen secreted by the testes.
• It is essential for male reproductive development, fertility, and maintenance of secondary sexual characteristics.
• Deficiency may cause reduced libido, impaired spermatogenesis, infertility, and delayed puberty.

Source

• Testosterone is produced mainly by Leydig cells in the testes.
• Smaller amounts are produced by the adrenal cortex.
• In females, low levels arise from ovaries and adrenal glands.
• During pregnancy, steroid production also occurs in the placenta.
• Testosterone is a C19 steroid hormone derived from cholesterol.
• Like other steroid hormones, it is lipid soluble and diffuses through cell membranes.

Structure, Synthesis and Secretion

• In Leydig cells, testosterone is synthesized from cholesterol through several enzymatic steps.
• Important intermediates include pregnenolone, progesterone, dehydroepiandrosterone, and androstenedione.
• Final conversion produces testosterone.
• Steroidogenic pathways differ slightly among endocrine organs because of different enzyme expression.
• Testosterone secretion is stimulated mainly by luteinizing hormone from the anterior pituitary.
• It is released in a pulsatile pattern and shows diurnal variation, often highest in the morning.
• Normal adult male production is approximately 4–10 milligrams daily.
• Typical total testosterone concentration in adult males is about 300–1000 nanograms per deciliter.
• Female levels are much lower, usually 15–70 nanograms per deciliter depending on age and laboratory method.
• By 5-alpha reductase, testosterone is converted to dihydrotestosterone (DHT).
• Supports development of male genital organs during fetal life.
• Maintains spermatogenesis with follicle-stimulating hormone.
• Promotes muscle mass, bone density, body hair growth, erythropoiesis, and sexual function.
• Some testosterone converts to dihydrotestosterone or estradiol in target tissues.

Metabolism

• About 98% of testosterone circulates bound to plasma proteins, while a small fraction remains free and biologically active.
• Most binding occurs to sex hormone-binding globulin and albumin.
• Free testosterone enters target tissues and undergoes local conversion.
• By aromatase, it can also be converted to estradiol.
• DHT is a more potent androgen because it binds androgen receptors more strongly than testosterone.
• DHT is important for external genital development, body hair growth, and prostate enlargement.
• Testosterone therefore acts partly as a prohormone for tissue-specific metabolites.
• In the liver, testosterone is metabolized into inactive compounds, including 17-ketosteroids such as androsterone and etiocholanolone.
• These metabolites are excreted mainly in urine after conjugation.
• Urinary ketosteroids originate from both adrenal and testicular androgens.

Testicular Estrogen

• The main circulating estrogens are estradiol and estrone, with estradiol being the more potent form.
• In men, plasma estradiol is usually about 20–50 picograms/milliliter.
• Only a small proportion of male estrogen is produced directly by the testes.
• Most estrogen forms by aromatization of testosterone in adipose tissue and other peripheral tissues.
• Male estrogen production may increase with advancing age.

Mechanism of Action

• Testosterone is a steroid hormone that enters target cells and binds intracellular androgen receptors.
• The hormone-receptor complex regulates gene transcription and protein synthesis.
• Two major functional pathways operate in tissues: testosterone pathway and dihydrotestosterone (DHT) pathway.

DHT pathway

• In prostate, external genitalia, skin, and some hair follicles, testosterone is converted to DHT by 5-alpha reductase.
• DHT binds androgen receptors strongly and promotes external virilization.
• It contributes to facial hair growth, prostate enlargement, penile growth, and male-pattern hair loss.

Testosterone Pathway

• Testosterone can act directly through androgen receptors.
• It supports spermatogenesis, muscle growth, libido, erythropoiesis, and feedback regulation of gonadotropin secretion.

Physiological Actions

• Testosterone is an anabolic androgen that promotes growth of male reproductive organs and secondary sexual characteristics.
• Relative androgen potency is: DHT > testosterone > androstenedione > dehydroepiandrosterone.

Development of Secondary Sex Characteristics

• Testosterone is the main hormone responsible for male pubertal changes.
• It develops and maintains secondary sexual characteristics after puberty.
• Many effects are mediated directly or through dihydrotestosterone in target tissues.

External Genitalia

• The penis increases in length and girth during puberty.
• The scrotum enlarges, becomes more rugose, and shows increased pigmentation.
• Testicular volume also increases, which is an early sign of puberty.

Internal Genitalia

• The seminal vesicles enlarge and begin active fructose-rich secretion.
• The prostate gland increases in size and secretory activity.
• Bulbourethral gland secretion also becomes more active.
• These changes support semen formation and fertility.

Body Hair Distribution

• Testosterone stimulates growth of androgen-sensitive hair.
• Axillary and pubic hair increase during puberty.
• Facial hair develops as moustache and beard.
• Chest, abdominal, and perianal hair may appear depending on genetics.
• Pubic hair spreads in a typical male diamond or upward-triangle pattern.
• Scalp hairline may recede in genetically susceptible individuals.

Skin Changes

• Skin becomes thicker and more oily due to increased sebaceous gland activity.
• This may predispose to acne vulgaris during adolescence.
• Genital skin may become more pigmented and sensitive.

Voice Changes

• The larynx enlarges and vocal cords lengthen and thicken.
• Voice becomes deeper and lower pitched.
• Temporary voice instability may occur during puberty.

Mental and Behavioral Effects

• Increased androgen activity may influence confidence, competitiveness, libido, and sexual interest.
• Emotional changes during puberty are also affected by social and psychological factors.

Body Configuration

• A pubertal growth spurt increases height and body size.
• Shoulders broaden relative to the pelvis.
• Lean body mass increases, giving a more typically male physique.

Musculoskeletal Effects

• Testosterone increases muscle protein synthesis and muscle hypertrophy.
• Bone growth accelerates during puberty.
• It contributes to increased bone density and skeletal strength.
• Final closure of epiphyseal growth plates occurs mainly after estrogen conversion from testosterone, limiting further height gain.

Clinical Note

• Delayed or absent androgen action may impair these pubertal changes and suggest endocrine disorders.

Effects on Spermatogenesis

• Testosterone is essential for normal sperm production and fertility.
• It helps initiate spermatogenesis at puberty.
• Adequate intratesticular testosterone is required to maintain sperm production during adult life.
• It has a major role in later maturation stages, especially spermiogenesis.
• Deficiency may reduce sperm count and impair fertility.

Effects during Embryonic Life

• In the male fetus, testosterone is crucial for sexual differentiation during early gestation.
• It promotes development of the Wolffian ducts into epididymis, vas deferens, and seminal vesicles.
• Testosterone and dihydrotestosterone help formation of external genitalia, including penis and scrotum.
• These hormones also contribute to normal testicular descent.

Anabolic Effects

• Testosterone increases protein synthesis and reduces protein breakdown.
• This supports growth of skeletal muscle and lean body mass.
• It promotes bone growth and increases bone mineral density.
• Mild retention of sodium, water, and minerals may occur.
• Synthetic androgens have been used medically in selected wasting conditions, though misuse carries risks.

Effects on Brain

• Many brain regions contain androgen receptors, especially the hypothalamus, limbic system, and preoptic area.
• Testosterone influences libido, mood, motivation, and some aspects of behavior.
• In certain brain tissues, testosterone can be converted to estrogen by aromatase.
• Sex steroid exposure contributes to developmental differences in some neural circuits.

Other Effects

• Testosterone exerts negative feedback on the hypothalamus and pituitary.
• It suppresses gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone secretion when levels are adequate.
• It stimulates erythropoiesis, increasing red blood cell production.
• Excess testosterone may cause acne, infertility, polycythemia, and prostate-related concerns.

Other Testicular Hormones

• Other testicular hormones include androgens, inhibin, activin, and follistatin.
• Small amounts of estrogen are formed in Sertoli cells by aromatization of androgens.

Androgens

• Testicular androgens include testosterone, androstenedione, and dihydrotestosterone.
• Testosterone is the principal androgen secreted by the testes.

Inhibin

Source

• Inhibin is secreted by Sertoli cells of the testes in males.
• In females, it is produced mainly by granulosa cells of the ovaries.

Types and Structure

• Two main forms are present: Inhibin A and Inhibin B.
• Inhibins are glycoprotein hormones composed of two subunits: one alpha and one beta subunit.
• The beta subunit exists as beta A or beta B forms.
• Inhibin A contains alpha-beta A, while Inhibin B contains alpha-beta B.
• Inhibin B is the major form involved in regulation of follicle-stimulating hormone in males.
• Beta subunits can also combine to form activins, which have different physiological actions.

Functions

• The principal function of inhibin is negative feedback inhibition of follicle-stimulating hormone release from the anterior pituitary.
• In males, serum Inhibin B reflects Sertoli cell activity and ongoing spermatogenesis.
• Reduced inhibin levels may suggest impaired testicular function or decreased sperm production.

Activin

• Activin is a peptide hormone produced by Sertoli cells and many other tissues.
• It is formed from combinations of beta subunits related to inhibin.
• Activin stimulates follicle-stimulating hormone secretion from the anterior pituitary.
• It also participates in embryonic development, gonadal growth, and hematopoiesis.

Follistatin

• Follistatin is a binding protein present in several isoforms.
• It binds and neutralizes activin, reducing its biological effects.
• By inhibiting activin, follistatin lowers follicle-stimulating hormone secretion.
• It also has local paracrine roles in spermatogenesis.

Regulation of Testicular Functions

• The testes perform endocrine and reproductive functions, especially secretion of testosterone and support of spermatogenesis.
• Regulation occurs through the hypothalamic-pituitary-gonadal axis.

Hypothalamic Control

• The hypothalamus releases gonadotropin-releasing hormone in a pulsatile manner.
• This hormone stimulates the anterior pituitary to release luteinizing hormone and follicle-stimulating hormone.

Pituitary Control

• Luteinizing hormone acts on Leydig cells to stimulate testosterone production.
• Follicle-stimulating hormone acts on Sertoli cells.
• Sertoli cells produce androgen-binding protein, inhibin, and factors that support spermatogenesis.

Steroid Feedback

• Testosterone exerts negative feedback on the hypothalamus and pituitary, reducing gonadotropin release.
• Inhibin selectively suppresses follicle-stimulating hormone secretion.
• This feedback system helps maintain stable reproductive function.

Table 67.1: Average plasma concentration (μg/lit) of androgens in adult male.

Androgen (Adult Male Plasma)	Approximate Mean Concentration (µg/L)
Testosterone	6.5
Androstenedione	1.5
Dihydrotestosterone (DHT)	0.5

Values are average estimates and may vary with age, laboratory method, and time of sampling.

Testicular Abnormalities

Cryptorchidism

• Cryptorchidism is failure of one or both testes to descend into the scrotum before birth.
• The testis normally descends from the posterior abdominal wall through the inguinal canal into the scrotum.
• Common locations of an undescended testis include the inguinal canal or abdomen.
• Testicular descent is influenced by anti-Müllerian hormone, testosterone, gubernaculum development, and neural factors.
• Descent usually completes during late fetal life or early infancy.

Treatment

• Some testes descend spontaneously in early infancy.
• Persistent cases usually require orchiopexy, ideally in early childhood.
• Hormonal therapy has limited success and is less commonly used.

Complications

• Higher intra-abdominal temperature may impair spermatogenesis and future fertility.
• Risk of testicular malignancy, torsion, and inguinal hernia is increased.

Male Hypogonadism

• Male hypogonadism is reduced testicular function causing low testosterone, impaired spermatogenesis, or both.
• Two major types are hypergonadotropic and hypogonadotropic hypogonadism.

Hypergonadotropic Hypogonadism

• This results from primary testicular failure.
• Testosterone is low, while luteinizing hormone and follicle-stimulating hormone are elevated.

Hypogonadotropic Hypogonadism

• This occurs due to hypothalamic or pituitary disorders such as tumors, genetic defects, or systemic illness.
• Gonadotropin levels are low or inappropriately normal.
• After puberty, patients may develop reduced libido, infertility, fatigue, and gradual regression of secondary sexual characteristics.
• Childhood onset may cause delayed puberty, tall eunuchoid body proportions, small genitalia, sparse body hair, and low muscle mass.

Androgen Secreting Tumors

• Leydig cell tumors may secrete excess androgens.
• In prepubertal boys, this can cause precocious puberty with early virilization and rapid growth.