Lecture 38- Male Reproductive Physiology_2023.pdf

MALE REPRODUCTIVE PHYSIOLOGY • Master of Arts in Biomedical Sciences • Bluefield College, VCOM Campus LEARNING OBJECTIVES 1. Describe the physiological functions of the major components of the male reproductive tract. 2. Describe spermatogenesis and the role of different cell types in this...

MALE REPRODUCTIVE PHYSIOLOGY • Master of Arts in Biomedical Sciences • Bluefield College, VCOM Campus LEARNING OBJECTIVES 1. Describe the physiological functions of the major components of the male reproductive tract. 2. Describe spermatogenesis and the role of different cell types in this process. 3. Describe the endocrine regulation of testicular function: the role of the GnRH pulse generator, FSH, LH, testosterone, and inhibin. 4. Identify the cell of origin for testosterone, its biosynthesis, mechanism of transport within the blood, how it is metabolized and how it is eliminated. ANATOMY The anatomy of the male internal genitalia and accessory sex organs 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 then emptying into the internal urethra. • Prostatic ducts also empty from the prostate gland into the ejaculatory duct and from there into the prostatic urethra. • Urethra is the last connecting link from the testis to the exterior. The urethra is supplied with mucus derived from a large number 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. ANATOMY OF THE MALE SEXUAL ORGANS • The testis is composed of up to 900 coiled seminiferous tubules, each averaging more than one-half meter long, in which the sperm are formed. The sperm then 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. A, The male reproductive system. B, The internal structure of the testis and the relation of the testis to the epididymis. A, Modified from Bloom V, Fawcett DW: Textbook of Histology, 10th ed. Philadelphia: WB Saunders, 1975. B, Modified from Guyton AC: Anatomy and Physiology. Philadelphia: Saunders College Publishing, 1985 MALE • The male reproductive system consists of two essential elements: the gonads and the complex array of glands and conduits that constitute the sex accessories. • The gonads in males are the testes, and they are responsible for the production of gametes, the haploid cells (spermatozoa) necessary for sexual reproduction. The gonads also synthesize and secrete the hormones that are necessary for functional conditioning of the sex organs, control of gonadotropin secretion, and modulation of sexual behavior. • The testis is largely composed of seminiferous tubules and the interstitial cells of Leydig, located in the spaces between the tubules. • The seminiferous tubules are lined by seminiferous epithelium, which rests on the inner surface of a basement membrane • The basement membrane is supported by a thin lamina propria externa. MALE • The sex accessories in the male include 1. the paired epididymides, 2. the vas deferens, 3. the seminal vesicles, 4. the ejaculatory ducts • Also included among the sex accessories are the prostate, the bulbourethral (Cowper's) glands, the urethra, and the penis. • The primary role of the male sex accessory glands and ducts is to store and transport spermatozoa to the exterior at the proper time, thus enabling them to come in contact with and fertilize female gametes. PUBERTY OCCURS IN FIVE DEFINED STAGES • During the final month of fetal life, the testes descend into an integumentary pouch called the scrotum. • The inguinal canals through which the testes descend are sealed off shortly after birth. • Because the internal temperature of the testicle must be closely regulated for optimum function, localization of the testes within the scrotum appears to be a necessary adaptation for testicular function. • Aberrant retention of the testes in the abdominal cavity (cryptorchidism) causes marked damage to the seminiferous tubules and diminished testicular function. • The range of onset of normal male puberty extends from 9 to 14 years. Males complete pubertal development within 2 to 4½ years. • In a normal male, the first sign of puberty (stage 2) is enlargement of the testes to greater than 2.5 cm. • Testicular enlargement is mainly a result of growth of the seminiferous tubules, but Leydig cell enlargement contributes as well. • Androgens from the testes are the driving force behind secondary sexual development, although adrenal androgens play a role in normal puberty. THE TANNER METHOD OF DESCRIBING THE STAGES OF PUBERTAL DEVELOPMENT STAGE GENITAL DEVELOPMENT PUBIC HAIR 1 Preadolescent. The penis, scrotum, and testes are the same size-relative to body size-as in a young child Preadolescent. No pubic hair is present, only vellus hair, as on the abdomen 2 Scrotum and testes are enlarged Pubic hair is sparse, mainly at the base of the penis 3 Penis is enlarged, predominantly in length. Scrotum and testes are further enlarged Pubic hair is darker, coarser, and curlier and spreads above the pubis 4 Penis is further enlarged in length and also in diameter. Scrotum and testes are further enlarged Pubic hair is of the adult type, but covers an area smaller than in most adults Adult pattern Adult pattern STAGES IN MALE PUBERTY 5 ANDROGENS DETERMINE MALE SECONDARY SEXUAL CHARACTERISTICS • The male sex steroids, which are known as androgens, affect nearly every tissue in the body, including the brain. The development of both the external and the internal genitalia depends on male sex hormones. • Androgens stimulate adult maturation of the external genitalia and accessory sexual organs, including the penis, the scrotum, the prostate, and the seminal vesicles. • Androgens also determine the male secondary sexual characteristics, which include deepening of the voice, as well as evolving male patterns of hair growth. • The effects on the voice are a result of androgen-dependent effects on the size of the larynx, as well as the length and thickness of the vocal cords. MUSCLE DEVELOPMENT AND GROWTH ARE ANDROGEN-DEPENDENT PROCESSES • Androgens have anabolic effects, including stimulation of linear body growth, nitrogen retention, and muscular development in the adolescent and mature male. • The biologic effects of testosterone and its metabolites have been classified according to their tissue sites of action. • Effects that relate to growth of the male reproductive tract or development of secondary sexual characteristics are referred to as androgenic, • whereas the growth-promoting effects on somatic tissue are called anabolic. • These androgenic and anabolic effects are two independent biologic actions of the same class of steroids. Experimental evidence, however, indicates that these responses are organ specific and that the molecular mechanisms that initiate androgenic responses are the same as those that stimulate anabolic activity. HYPOTHALAMIC-PITUITARYGONADAL AXIS AND CONTROL OF MALE SEXUAL FUNCTIONS • 1. 2. The male hypothalamic-pituitary-gonadal axis controls two primary functions: production of male gametes (spermatogenesis) in the seminiferous tubules and Androgen biosynthesis in the Leydig cells in the testes. The hypothalamus produces gonadotropin-releasing hormone (GnRH), which stimulates the gonadotrophs in the anterior pituitary to secrete the two gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). HYPOTHALAMIC-PITUITARYGONADAL AXIS AND CONTROL OF MALE SEXUAL FUNCTIONS • Another view SPERMATOGENESIS • Early during embryogenesis, the primordial germ cells migrate to the gonad, where they become spermatogonia. Beginning at puberty, the spermatogonia undergo many rounds of mitotic division. SPERMATOGENESIS • At puberty the spermatogonia begin to undergo mitotic division and continually proliferate and differentiate through definite stages of development to form sperm. STEPS OF SPERMATOGENESIS • Spermatogenesis occurs in the seminiferous tubules during active sexual life as the result of stimulation by anterior pituitary gonadotropic hormones. Spermatogenesis begins in the male at an average age of 13 years and continues throughout most of the remainder of life but decreases markedly in old age. • Cell divisions during spermatogenesis. During embryonic development, the primordial germ cells migrate to the testis, where they become spermatogonia. At puberty (usually 12 to 14 years after birth), the spermatogonia proliferate rapidly 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 spermatids, which differentiate to form spermatozoa. SPERM MATURATION IN THE EPIDIDYMIS Progressive increase in forward motility Increased ability to fertilize Maturation of acrosome Molecular reorganization of the plasma membrane: Lipids (stabilization of plasma membrane) Proteins (shedding as well as acquisition of new proteins) Ability to bind to zona pellucida Acquisition of receptors for proteins of the zona Pellucida HORMONAL FACTORS THAT STIMULATE SPERMATOGENESIS • The role of hormones in reproduction is discussed later in detail; for now, note that several hormones play essential roles in spermatogenesis. Some of these roles are as follows: • 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, which is the first stage in forming sperm. • 2. Luteinizing hormone, secreted by the anterior pituitary gland, stimulates the Leydig cells to secrete testosterone. • 3. Follicle-stimulating hormone, also secreted by the anterior pituitary gland, stimulates the Sertoli cells; without this stimulation, conversion of the spermatids to sperm (the process of spermiogenesis) will not occur. • 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 (as well as most of the other body hormones) is necessary for controlling background metabolic functions of the testes. Growth hormone specifically promotes early division of the spermatogonia; in its absence, as in pituitary dwarfs, spermatogenesis is severely deficient or absent, thus causing infertility. SERTOLI CELLS • The Sertoli cells are generally regarded as support or "nurse" cells for the spermatids • Sertoli cells are large polyhedral cells extending from the basement membrane toward the lumen of the seminiferous tubule. • Spermatids are located adjacent to the lumen of the seminiferous tubules during the early stages of spermiogenesis and are surrounded by processes of Sertoli-cell cytoplasm. • Tight junctions connect adjacent Sertoli cells. In addition, gap junctions between the Sertoli cells and developing spermatozoa may represent a mechanism for transferring material between these two types of cells. • Release of the spermatozoa from the Sertoli cell has been called spermiation. • Spermatids progressively move toward the lumen of the tubule and eventually lose all contact with the Sertoli cell after spermiation. THE LEYDIG CELLS OF THE TESTIS SYNTHESIZE AND SECRETE TESTOSTERONE • Cholesterol is the obligate precursor for androgens, as well as other steroids produced by the testis. • The Leydig cell can synthesize cholesterol de novo from acetyl coenzyme A or take it up as low-density lipoproteins from the extracellular fluid by receptor mediated endocytosis • The two sources appear to be equally important in humans. BIOSYNTHESIS OF TESTOSTERONE LEYDIG-AND SERTOLI-CELL PHYSIOLOGY • The Leydig cell (left) has receptors for LH. The binding of LH increases testosterone synthesis. The Sertoli cell (right) has receptors for FSH. • FSH promotes the synthesis of androgen-binding protein (ABP), aromatase, growth factors, and inhibin. • There is crosstalk between Leydig cells and Sertoli cells. The Leydig cells make testosterone, which acts on Sertoli cells. Conversely, the Sertoli cells convert some of this testosterone to estradiol (because of the presence of aromatase), which can act on the Leydig cells. F O L L I C L E - S T I M U L AT I N G H O R M O N E S T I M U L AT E S S E RTO L I C E L L S TO S Y N T H E S I Z E A N U M B E R O F P RO D U C T S N E E D E D B Y B OT H L E Y D I G C E L L S A N D D E V E L O P I N G S P E R M ATO G O N I A • The Sertoli cells are the primary testicular site of FSH action • FSH also regulates Leydig-cell physiology via effects on Sertoli cells. • Several proteins are synthesized in response to FSH. Some are important for steroid action: • 1) FSH leads to the synthesis of androgen-binding protein (ABP), which is secreted into the luminal space of the seminiferous tubule, near the developing sperm cells. ABP helps keep local testosterone levels high • 2) Second, FSH causes the synthesis of a P-450 aromatase. Inside the Sertoli cells, this enzyme converts testosterone, which diffuses from the Leydig cells to the Sertoli cells, into estradiol. • 3) FSH leads to the production of a number of growth factors and other products by Sertoli cells that support sperm cells and spermatogenesis. • These substances significantly increase the number of spermatogonia, spermatocytes, and spermatids in the testis. • Plasma levels of FSH, LH, and testosterone from puberty to adulthood Plasma testosterone versus age in human males • Other Organs-Such as Adipose Tissue, Skin, and the Adrenal Cortex-also Produce Testosterone and Other Androgens • In men who are between the ages of 25 and 70 years, the rate of testosterone production remains relatively constant TESTOSTERONE AND THE AGING MALE • For a long time, the abrupt hormonal alterations that signal the dramatic changes of female menopause were believed to have no correlate in males. • We now know that men do experience a gradual decline in their serum testosterone levels and that this decline is closely correlated with many of the changes that accompany aging: decreased bone formation, muscle mass, growth of facial hair, appetite, and libido. • The blood hematocrit also decreases. • Testosterone replacement can reverse many of these changes by restoring muscle and bone mass and correcting the anemia. • Although the levels of both total and free testosterone decline with age, levels of luteinizing hormone are frequently not elevated. This finding is believed to indicate that some degree of hypothalamic-pituitary dysfunction accompanies aging THANK YOU