Reproductive and Hormonal Functions of the Male PDF

Reproductive and Hormonal Functions of the Male Prof. Dr. Senol DANE  Male reproductive functions can be divided into three major subdivisions: – (1) spermatogenesis (the formation of sperm) – (2) performance of the male sexual act – (3) the hormonal regulation of male...

Reproductive and Hormonal Functions of the Male Prof. Dr. Senol DANE  Male reproductive functions can be divided into three major subdivisions: – (1) spermatogenesis (the formation of sperm) – (2) performance of the male sexual act – (3) the hormonal regulation of male reproductive functions Physiological Anatomy of the Male Sexual Organs The testis is composed of up to 900 coiled seminiferous tubules (more than one-half meter) in which the sperm are formed. The sperm empty into the epididymis, which is another coiled tube about 6 meters long. The epididymis leads into the vas deferens, which enlarges into the ampulla of the vas deferens immediately before the vas enters the body of the prostate gland.  https://www.youtube.com/ watch?v=qz7uLX-AOlk Physiological Anatomy of the Male Sexual Organs Two seminal vesicles, one located on each side of the prostate, empty into the prostatic end of the ampulla, and the contents from both the ampulla and the seminal vesicles pass into an ejaculatory duct leading through the body of the prostate gland and emptying into the internal urethra. Prostatic ducts empty from the prostate gland into the ejaculatory duct and then into the prostatic urethra. Physiological Anatomy of the Male Sexual Organs Finally, the urethra is the last connecting link from the testis to the exterior. The urethra is supplied with mucus derived from a lot of minute urethral glands located along its entire extent and even more so from bilateral bulbourethral glands (Cowper glands) located near the origin of the urethra.  SPERMATOGENESIS In the embryo, the primordial germ cells migrate into the testes and become immature germ cells (spermatogonia). They lie in two or three layers of the inner surfaces of the seminiferous tubules. At puberty, the spermatogonia begin to undergo mitotic division and proliferate and differentiate through sperm formation.  STEPS OF SPERMATOGENESIS Spermatogenesis occurs in the seminiferous tubules during active sexual life with stimulation by gonadotropic hormones (FSH and LH). Spermatogenesis begins at an average age of 13 years and continues throughout most of the remainder of life but decreases in old age.  In the first stage of spermatogenesis, the spermatogonia migrate among Sertoli cells toward the central lumen of the tubule. The Sertoli cells are large and have overflowing cytoplasmic envelopes. They surround the spermatogonia all the way to the central lumen of the tubule.  Blood–testis barrier It is a physical barrier between the blood vessels and the seminiferous tubules. It is formed between Sertoli cells and isolates the further developed stages of germ cells from the blood. A more correct term is the "Sertoli cell barrier".  Meiosis Spermatogonia that cross the barrier into the Sertoli cell layer become progressively modified and enlarged to form large primary spermatocytes. Primary spermatocytes undergo meiotic division to form two secondary spermatocytes. After another few days, these secondary spermatocytes divide to form spermatids that are eventually modified to become spermatozoa (sperm). In embryo, the primordial germ cells migrate to the testis, where they become spermatogonia. At puberty, the spermatogonia proliferate by mitosis. Some begin meiosis to become primary spermatocytes and continue through meiotic division I to become secondary spermatocytes. After completion of meiotic division II, the secondary spermatocytes produce  During the change from the spermatocyte stage to the spermatid stage, the 46 chromosomes (23 pairs of chromosomes) of the spermatocyte are divided. 23 chromosomes go to one spermatid and the other 23 go to the second spermatid.  The chromosomal genes are divided. Only one half of the genetic characteristics of the fetus are provided by the father, with the other half being derived from the oocyte provided by the mother. The entire period of spermatogenesis, from spermatogonia to spermatozoa, takes about 74 days.  Sex Chromosomes In each spermatogonium, one of the 23 pairs of chromosomes carries the genetic information that determines the sex of each eventual offspring. This pair is composed of one X chromosome and one Y chromosome. During meiotic division, the male Y chromosome goes to one spermatid that then becomes a male sperm, and the female X chromosome goes to another spermatid that becomes a female sperm.  Formation of Sperm When the spermatids are first formed, they are epithelioid cells, but soon they begin to differentiate and elongate into sperm. Each sperm is composed of a head and a tail. The head comprises the condensed nucleus of the cell, with only a thin cytoplasmic and cell membrane layer around its surface. Structure of the human spermatozoon  Formation of Sperm On the outside of the anterior two thirds of the head is a thick cap called the acrosome that is formed mainly from the Golgi apparatus. The acrosome contains several lysosomal enzymes (hyaluronidase and proteolytic enzymes). These enzymes play important roles in allowing the sperm to enter the ovum and fertilize it.  The tail of the sperm (the flagellum) has 3 major components: – (1) a central skeleton constructed of 11 microtubules, collectively called the axoneme (like cilia) – (2) a thin cell membrane covering the axoneme – (3) a collection of mitochondria surrounding the axoneme in the proximal portion of the tail (the body of the tail).  Back-and-forth movement of the tail provides sperm motility. This movement results from a rhythmical longitudinal sliding motion between the anterior and posterior tubules in the axoneme. The energy is supplied in the form of ATP, which is synthesized by the mitochondria in the tail body. Normal sperm move in a fluid medium at a velocity of 1 to 4 mm/min (to move through the female genital tract).  Hormonal Factors in Spermatogenesis The essential roles of hormones in spermatogenesis: 1. Testosterone, secreted by the Leydig cells located in the interstitium of the testis, is essential for growth and division of the testicular germinal cells. 2. LH, secreted by the anterior pituitary gland, stimulates the Leydig cells to secrete testosterone. 3. FSH, secreted by the anterior pituitary gland, stimulates the Sertoli cells; for the conversion of the spermatids to sperm (the process of spermiogenesis).  Hormonal Factors in Spermatogenesis 4. Estrogens, formed from testosterone by the Sertoli cells when they are stimulated by follicle-stimulating hormone, are probably also essential for spermiogenesis. 5. Growth hormone is necessary for controlling metabolic functions of the testes. Growth hormone promotes early division of the spermatogonia; in its absence, as in pituitary dwarfs, spermatogenesis is severely deficient, causing infertility.  Maturation of Sperm in the Epididymis After formation in the seminiferous tubules, the sperm require several days to pass through the tubule of the epididymis. Sperm in the seminiferous tubules or the early portions of the epididymis is nonmotile and cannot fertilize an ovum. After the sperm have been in the epididymis for 18 to 24 hours, they win the capability of motility.  Storage of Sperm in the Testes The two testes form up to 120 million sperm a day. Most of them are stored in the epididymis, less is stored in the vas deferens. Their fertility capability continues for at least a month. But, with a high level of sexual activity and ejaculations, they may be stored no longer than a few days.  Storage of Sperm in the Testes After ejaculation, the sperm become motile and capable of fertilizing the ovum, a process called maturation. The Sertoli cells and the epithelium of the epididymis secrete a special nutrient fluid that is ejaculated along with the sperm. This fluid contains hormones (testosterone and estrogens), enzymes, and special nutrients needed for sperm maturation.  Physiology of the Mature Sperm The normal motile, fertile sperm can move through the fluid medium at velocities of 1- 4 mm/min. The activity of sperm is enhanced in a neutral and alkaline medium, as exists in the ejaculated semen, but it is depressed in a mildly acidic medium. A strong acidic medium can cause the rapid death of sperm.  Physiology of the Mature Sperm The activity of sperm increases with increasing temperature, but so does the rate of metabolism, causing the life of the sperm to be shortened. Sperm can live for many weeks in the genital ducts of the testes, its life expectancy in the female genital tract is 1-2 days.  FUNCTION OF THE SEMINAL VESICLES Each seminal vesicle is a tortuous, loculated tube lined with a secretory epithelium that secretes a mucoid material containing fructose, citric acid, and other nutrient substances, as well as large quantities of prostaglandins and fibrinogen.  FUNCTION OF THE SEMINAL VESICLES During the process of emission and ejaculation, each seminal vesicle empties its contents into the ejaculatory duct shortly after the vas deferens empties the sperm. The fructose and other substances are of nutrient value for the sperm until one of the sperm fertilizes the ovum.  Prostaglandins help fertilization in two ways: (1) by reacting with the female cervical mucus to make it more receptive to sperm movement (2) by possibly causing backward, reverse peristaltic contractions in the uterus and fallopian tubes to move the sperm toward the ovaries (a few sperm reach the upper ends of the fallopian tubes within 5 minutes).  FUNCTION OF THE PROSTATE GLAND The prostate gland secretes a thin, milky fluid that contains calcium, citrate, phosphate ions, a clotting enzyme, and a profibrinolysin. During emission, the capsule of the prostate gland contracts simultaneously with the contractions of the vas deferens so that the fluid of the prostate gland adds to the semen. Alkaline characteristic of this fluid is important for successful fertilization because the fluid of the vas deferens is acidic owing to the presence of citric acid and metabolic end products of the sperm and inhibits sperm fertility.  FUNCTION OF THE PROSTATE GLAND Also, the vaginal secretions of the female are acidic (with a pH of 3.5 to 4.0). Sperm do not become motile until the pH of the fluids rises to about 6.0 - 6.5. The alkaline prostatic fluid helps neutralize the acidity of the other seminal fluids during ejaculation and enhances the motility and fertility of the sperm.  SEMEN Semen is ejaculated during the male sexual act and composed of the fluid and sperm from the vas deferens (10%), fluid from the seminal vesicles (almost 60%), fluid from the prostate gland (about 30%), and small amounts from the mucous and the bulbourethral glands. Seminal vesicle fluid is the last to be ejaculated and serves to wash the sperm through the ejaculatory duct and urethra.  SEMEN The average pH of the semen is about 7.5. The prostatic fluid gives the semen a milky appearance, and fluid from the seminal vesicles and mucous glands gives the semen a mucoid consistency. A clotting enzyme from the prostatic fluid causes the fibrinogen of the seminal vesicle fluid to form a fibrin coagulum that holds the semen in the deeper regions of the vagina.  SEMEN The coagulum then dissolves during the next 15-30 min. because of lysis by fibrinolysin formed from the prostatic profibrinolysin. In the early minutes after ejaculation, the sperm remain relatively immobile because of the viscosity of the coagulum. As the coagulum dissolves, the sperm simultaneously become highly motile.  SEMEN Sperm can live for many weeks in the male genital ducts, but their maximal life span is only 24-48 hours in female genital tracts. At lowered temperatures semen can be stored for several weeks, and when frozen at temperatures below −100°C, sperm have been preserved for years.  “Capacitation” of Spermatozoa Although spermatozoa are said to be “mature” when they leave the epididymis, their activity is held in check by multiple inhibitory factors secreted by the genital duct epithelia. When sperms are first expelled, they cannot fertilize the ovum. Multiple changes activate the sperm for the processes of fertilization. These changes are called capacitation of the spermatozoa, which requires from 1-10 hours.  Changes during Capacitation 1. The uterine and fallopian tube fluids wash away the various inhibitory factors that suppress sperm activity in the male genital ducts. 2. In the fluid of the male genital ducts, sperms are continually exposed to many floating vesicles from the seminiferous tubules containing large amounts of cholesterol.  Changes during Capacitation The cholesterol is continually added to the cellular membrane covering the sperm acrosome, toughening this membrane and preventing release of its enzymes. After ejaculation, the sperm deposited in the vagina swim away from the cholesterol vesicles upward into the uterine cavity, and they gradually lose much of their other excess cholesterol during the next few hours. The membrane at the head of the sperm (the acrosome) becomes much weaker  Changes during Capacitation 3. The membrane of the sperm becomes more permeable to calcium ions, so calcium enters the sperm in abundance and changes the activity of the flagellum, giving it a powerful motion in contrast to its previously weak motion.  Changes during Capacitation Also, the Ca ions cause changes in the cellular membrane of the acrosome, making it possible for the acrosome to release its enzymes rapidly and easily as the sperm penetrates the granulosa cell mass surrounding the ovum, and even more so as it attempts to penetrate the zona pellucida of the ovum. Without these changes, the sperm cannot make its way to the interior of the ovum to cause fertilization.  Acrosome Enzymes, the “Acrosome Reaction,” and Penetration of the Ovum Stored in the acrosome are large quantities of hyaluronidase and proteolytic enzymes. Hyaluronidase depolymerizes the hyaluronic acid polymers in the intercellular cement that holds the ovarian granulosa cells together. The proteolytic enzymes digest proteins in the structural elements of tissue cells that still adhere to the ovum.  Acrosome Enzymes, the “Acrosome Reaction,” and Penetration of the Ovum When the ovum is expelled from the ovarian follicle into the fallopian tube, it still carries with it multiple layers of granulosa cells. Before a sperm can fertilize the ovum, it must dissolute these granulosa cell layers, and then it must penetrate through the thick covering of the ovum itself, the zona pellucida. To achieve this penetration, the stored enzymes in the acrosome is released. Hyaluronidase is important in opening pathways between the granulosa cells so that the sperm can reach the ovum.  Acrosome Enzymes, the “Acrosome Reaction,” and Penetration of the Ovum When the sperm reaches the zona pellucida of the ovum, the membrane of the sperm binds specifically with receptor proteins in the zona pellucida. The entire acrosome rapidly dissolves and all the acrosomal enzymes are released. Within minutes, these enzymes open a penetrating pathway for passage of the sperm head through the zona pellucida to the inside of the ovum. Fertilization of the ovum. A, The mature ovum surrounded by the corona radiata. B, Dispersal of the corona radiata. C, Entry of the sperm. D, Formation of the male and female pronuclei. E, Reorganization of a full complement of chromosomes and beginning division of the ovum  Acrosome Enzymes, the “Acrosome Reaction,” and Penetration of the Ovum Within another 30 minutes, the cell membranes of the sperm head and of the oocyte fuse with each other to form a single cell. The genetic material of the sperm and the oocyte combine to form a completely new cell genome, containing equal numbers of chromosomes and genes from mother and father. This is the process of fertilization.  Only one sperm can enter the oocyte Within a few minutes after the first sperm penetrates the zona pellucida of the ovum, calcium ions diffuse inward through the oocyte membrane and cause exocytosis of multiple granules from the oocyte. These granules contain substances that prevent binding of additional sperm. Thus, almost never does more than one sperm enter the oocyte during fertilization.  https://www.youtube.com/watch?v=_ 5OvgQW6FG4 https://www.youtube.com/watch? v=_5OvgQW6FG4  Abnormal Spermatogenesis and Male Fertility The seminiferous tubular epithelium can be destroyed by several diseases. Bilateral orchitis of the testes resulting from mumps causes sterility in some males. Also, some male infants are born with degenerate tubular epithelia as a result of strictures in the genital ducts or other abnormalities. Another cause of sterility is excessive temperature of the testes.  Effect of Temperature on Spermatogenesis Increasing the temperature of the testes can prevent spermatogenesis by causing degeneration of most cells of the seminiferous tubules. The reason the testes are in the dangling scrotum is to maintain the temperature of these glands below the internal temperature of the body, about 2°C below the internal temperature.  On cold days, scrotal reflexes cause the musculature of the scrotum to contract, pulling the testes close to the body to maintain this 2-degree differential. Thus, the scrotum acts as a cooling mechanism for the testes, without which spermatogenesis might be deficient during hot weather.  Cryptorchidism Cryptorchidism is failure of a testis to descend from the abdomen into the scrotum. During development of the fetus, the testes are derived from the genital ridges in the abdomen. At about 3 weeks to 1 month before birth of the baby, the testes descend through the inguinal canals into the scrotum. If this descent does not occur, and as a result one or both testes remain in the abdomen, in the inguinal canal.  Cryptorchidism A testis that remains in the abdominal cavity is incapable of forming sperm. The tubular epithelium becomes degenerate, leaving only the interstitial structures of the testis. Higher temperature in the abdomen than in the scrotum is sufficient to cause this degeneration and to cause sterility. Operations to relocate the testes from the abdominal cavity into the scrotum before the adult sexual life must be performed.  Cryptorchidism Testosterone secreted by the fetal testes causes the testes to descend into the scrotum. Many instances of cryptorchidism are caused by abnormally formed testes that are unable to secrete enough testosterone. The surgical operation for cryptorchidism in these patients is not successful.  Effect of Sperm Count on Fertility The usual quantity of semen ejaculated during each coitus averages about 3.5 mL, and each mL of semen contains an average of about 120 million sperm. An average total of 400 million sperm are present in each ejaculate. If the number of sperm in each mL falls below about 20 million, the person is infertile.  Effect of Sperm Morphology and Motility on Fertility Occasionally a man has a normal number of sperm but is still infertile. In this situation, sometimes as many as one half of the sperm are abnormal physically, having two heads, abnormally shaped heads, or abnormal tails. The sperm appear to be structurally normal; they are either entirely or relatively nonmotile. If most of the sperm are morphologically abnormal or are nonmotile, the person is likely to be infertile, even though the remainder of the sperm is normal. Abnormal infertile sperm, compared with a normal sperm on the right.  MALE SEXUAL ACT-NEURONAL STIMULUS FOR PERFORMANCE OF THE MALE SEXUAL ACT The most important source of sensory signals for initiating the male sexual act is the glans penis. The glans has a sensitive sensory end- organ system that transmits into the CNS that special modality of sensation called sexual sensation. The slippery massaging action of intercourse on the glans stimulates the sensory end organs, and the sexual signals pass through the pudendal nerve, then through the sacral plexus into the sacral portion of the spinal cord, and finally up the cord to undefined areas of the brain.  Impulses from areas adjacent to the penis aids in stimulating the sexual act. For instance, stimulation of the anal epithelium, the scrotum, and perineal structures in general can send signals into the cord that add to the sexual sensation.  Sexual sensations can originate in areas of the urethra, bladder, prostate, seminal vesicles, testes, and vas deferens. One of the causes of “sexual drive” is filling of the sexual organs with secretions. Mild infection and inflammation of these sexual organs may stimulate sexual desire, and some “aphrodisiac” drugs, such as cantharidin, irritate the bladder and urethral mucosa, inducing inflammation and vascular congestion. Psychic Element of Male Sexual Stimulation Appropriate psychic stimuli enhance the ability of a person to perform the sexual act. Thinking sexual thoughts or even dreaming can initiate the male act, culminating in ejaculation. Indeed, nocturnal emissions during dreams, often called “wet dreams,” occur in many males.  Integration of the Male Sexual Act in the Spinal Cord Although psychic factors play an important part in the male sexual act, brain is not necessary for its performance. Appropriate genital stimulation can cause ejaculation after spinal cords have been cut above the lumbar region. The male sexual act results from reflex mechanisms integrated in the sacral and lumbar spinal cord, and these mechanisms can be initiated by either psychic stimulation from the brain or sexual stimulation from the sex organs. STAGES OF THE MALE SEXUAL ACT Penile Erection-Role of the Parasympathetic Nerves Penile erection is the first effect of male sexual stimulation, and the degree of erection is proportional to the degree of psychic or physical stimulation. Erection is caused by parasympathetic impulses that pass from the sacral portion of the spinal cord through the pelvic nerves to the penis. They release NO, VIP and acetylcholine. STAGES OF THE MALE SEXUAL ACT Penile Erection-Role of the Parasympathetic Nerves NO activates the enzyme guanylyl cyclase, causing increased formation of cyclic guanosine monophosphate (cGMP). The cGMP relaxes the arteries of the penis and the trabecular meshwork of smooth muscle fibers in the erectile tissue of the corpora cavernosa and corpus spongiosum. Blood flow into the penis increases, causing release of NO from the vascular endothelial cells and vasodilation. Erectile tissue of the penis  The erectile tissue (large cavernous sinusoids) becomes dilated tremendously when arterial blood flows rapidly into them under pressure while the venous outflow is partially occluded. High pressure within the sinusoids causes ballooning of the erectile tissue to such an extent that the penis becomes hard and elongated, which is the phenomenon of erection.  Lubrication is a Parasympathetic Function During sexual stimulation, the parasympathetic impulses cause the urethral and bulbourethral glands to secrete mucus. This mucus flows through the urethra during intercourse to aid in the lubrication during coitus. However, most of the lubrication of coitus is provided by the female sexual organs rather than by the male organs. Without lubrication, the male sexual act is seldom successful because unlubricated intercourse causes grating, painful sensations that inhibit rather than excite sexual sensations.  Emission and Ejaculation are Functions of the Sympathetic Nerves Emission and ejaculation are the culmination of the male sexual act. When the sexual stimulus becomes extremely intense, the reflex centers of the spinal cord begin to emit sympathetic impulses that leave the cord at T12 to L2 and pass to the genital organs through the hypogastric and pelvic sympathetic nerve plexuses to initiate emission.  Emission Emission begins with contraction of the vas deferens and the ampulla to cause expulsion of sperm into the internal urethra. Then, contractions of the muscular coat of the prostate gland followed by contraction of the seminal vesicles expel prostatic and seminal fluid into the urethra, forcing the sperm forward. All these fluids mix in the internal urethra with mucus already secreted by the bulbourethral glands to form the semen. The process to this point is emission.  Ejaculation The filling of the internal urethra with semen elicits sensory signals transmitted through the pudendal nerves to the spinal cord, giving the feeling of sudden fullness in the internal genital organs. Sensory signals excite rhythmical contraction of the internal genital organs and cause contraction of the ischiocavernosus and bulbocavernosus muscles that compress the bases of the penile erectile tissue.  Ejaculation These effects together cause rhythmical, wavelike increases in pressure in both the erectile tissue of the penis and the genital ducts and urethra, which “ejaculate” the semen from the urethra to the exterior. This final process is called ejaculation.  At the same time, rhythmical contractions of the pelvic muscles and some of the muscles of the body trunk cause thrusting movements of the pelvis and penis. This helps propel the semen into the deepest recesses of the vagina and perhaps even slightly into the cervix of the uterus.  Orgasm This entire period of emission and ejaculation is called the male orgasm. At its termination, the male sexual excitement disappears almost entirely within 1-2 minutes and erection ceases, a process called resolution.  TESTOSTERONE AND OTHER MALE SEX HORMONES  SECRETION, METABOLISM, AND CHEMISTRY OF THE MALE SEX HORMONE The testes secrete several male sex hormones (androgens), including testosterone, dihydrotestosterone, and androstenedione. Testosterone is much more abundant than the others. Much of the testosterone is converted into the more active hormone dihydrotestosterone in the target tissues.  Testosterone is formed by the interstitial cells of Leydig. Leydig cells are nonexistent during childhood and the testes do not secrete testosterone. They are numerous in the newborn infant for the first few months of life and in the adult male after puberty.  In tumors of the interstitial cells of Leydig, great quantities of testosterone are secreted. If the germinal epithelium of the testes is destroyed by x-ray treatment or excessive heat, the Leydig cells continue to produce testosterone. Interstitial cells of Leydig is located in the interstices between the seminiferous tubules  Secretion of Androgens The term “androgen” means any steroid hormone with masculinizing effects, including testosterone and male sex hormones produced elsewhere in the body besides the testes. The adrenal glands secrete androgens, although the total masculinizing activity of all these androgens is so slight (