Reproductive and Hormonal Functions of the male p1.docx

**Reproductive and Hormonal Functions of the male p1** Physiological anatomy of the male sexual organs The male reproductive system consists of 2 main elements: \- the *gonads,* the testes \- and the complex array of glands and ducts that constitute the sex accessory organs The testis is compo...

**Reproductive and Hormonal Functions of the male p1** Physiological anatomy of the male sexual organs The male reproductive system consists of 2 main elements: \- the *gonads,* the testes \- and the complex array of glands and ducts that constitute the sex accessory organs The testis is composed of up to 900 coiled *seminiferous tubules,* in which the sperm are formed. The spermatozoa are made in the **seminiferous tubules** of testes. From the capsule emanate several **septa** which subdivide the testis into about 250 incomplete lobules. The septa converge towards the midline of the posterior border, meeting along a thickening of the tunica albuginea called the **mediastinum testis**. Each lobule contains one to four **seminiferous tubules** embedded in a connective tissue **stroma**. Formation of sperm is supported by Sertoli cells, and Leydig cells. **Leydig cells** are \'interstitial\' cells (as they lie between the tubules). They contain many cholesterol-lipid droplets. The **Leydig cells** make and secrete **testosterone**, in response to **luteinizing hormone** **Testosterone** promotes production of spermatozoa, secretion from the accessory sex glands, and acquisition of male secondary characteristics. This process does not start until puberty when LH stimulates the **Leydig cells** to produce testosterone.  Sertoli cells sit on a basal membrane. Laterally they stand in direct contact with one another and with the germ cells. Each Sertoli cells is bound together with the neighboring cell through "tight junctions". These divide the tubules into two separate compartments. The mitotic spermatogonia remain in the **basal compartment**. Differentiating progeny enter the **adluminal compartment**, and are sealed off from the basal compartment. The tight junctions produced the named **blood-testis barrier** that restricts the diffusion of substances from the interstitum and blood vessels, and thus allows the Sertoli cell to determine the microenvironment above the junctions. In the adluminal compartment, the environment is controlled by the Sertoli cell. Meiosis and the differentiation of spermatids occurs in the adluminal compartment. The inter-Sertoli cell junctions transiently remodel to allow germ cells to move from the basal to the adluminal compartments, whilst protecting the functionality of the barrier. The **basal compartment** contains spermatogonia with doubled DNA, before the 1st meiosis. In the **adluminal compartment** are the spermatocytes, spermatids and spermatozoa. The \"tight-junction\" as a blood-testicle-barrier keeps spermatozoa from getting into the blood circulation or the lymphatic systems. **This is important because the immune system would produce antibodies against the antigens on the membrane of the monoploid spermatozoa, leading to an autoimmune-orchitis and thus to sterility.** The completely transformed sperm then goes into the *epididymis,* which leads into the *vas deferens.* The vas deferens enlarges into the *ampulla of the vas deferens* immediately before entering the body of the *prostate gland.* The 2 *seminal vesicles,* located on the sides 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. The *urethra* is the last connecting link from the testis to the exterior. The urethra is supplied with an alkaline mucus derived from the *urethral* *glands* located along its entire extent and from the bilateral *bulbourethral glands* (Cowper glands) located near the origin of the urethra. This mucus is called pre-ejacu-late and neutralize the acidic urinary pH. The cavernous smooth musculature and the smooth muscles of the arteriolar and arterial walls, plays a key role in the erectile process. In the flaccid state, these smooth muscles are tonically contracted, allowing only a small amount of arterial flow for nutritional purposes. The blood partial pressure of oxygen (PO2) is about 35mmHg range. The flaccid penis is in a moderate state of contraction.  Puberty *During childhood the hypothalamus does not secrete significant amounts of GnRH* due to the inhibitory effect on hypothalamic secretion of GnRH induced by any circulating sex steroid hormones. At puberty, the secretion of GnRH increases and adult sexual life begins. Nutritional deprivation delays puberty by repressing reproductive neuroendocrine function. Kisspeptin expression was shown to be high and to increase during puberty in the infundibular nucleus of the medium basal hypothalamus (MBH) in male and female. This pubertal increase in kisspeptin is accompanied by parallel changes in GnRH pulses, which suggests a connection between the increase in kisspeptin and the pubertal changes in GnRH pulses. Genes that inhibit kisspeptin synthesis in childhood and induce kisspeptin synthesis after puberty have been found. Spermatogenesis During formation of the embryo, the *primordial germ cells* migrate into the testes and become s*permatogonia,* which lie in 2-3 layers of the inner surfaces of the *seminiferous tubules*. Spermatogonia, during puberty, begin to undergo mitotic division and proliferate and differentiate until forming sperm. Steps of spermatogenesis Spermatogenesis takes place in the seminiferous tubules when stimulated by anterior pituitary gonadotropic hormones, beginning at an average age of 13 years and throughout most of the life but decreasing in old age. In the first stage of spermatogenesis, the spermatogonia migrate among *Sertoli cells* toward the central lumen of the seminiferous tubule. Formation of sperm From the primordial germ cells of the fetus to the spermatids in the sexual mature male, all the cells have epithelioid aspect. When spermatids differentiate into spermatozoa, they elongate and each spermatozoon is composed of a *head* and a *tail*. Sperm The head has the nucleus of the cell with only a thin cytoplasmic and cell membrane layer around its surface. On the outside of the anterior two thirds of the head is the *acrosome,* formed mainly from the Golgi apparatus. Acrosome contains enzymes similar to those found in lysosomes of the typical cell, like *hyaluronidase* and *proteolytic enzymes,* that allow the sperm to enter the ovum and fertilize it.  Meiosis Spermatogonia cross the barrier into the Sertoli cell layer and they modified and enlarged to form *primary* *spermatocytes*. Each of these, undergoes meiotic division to form 2 *secondary spermatocytes.* After another few days, these too divide to form *spermatids* that are eventually modified to become *spermatozoa*(sperm). The spermatocyte still have the 46 chromosomes (23 pairs of chromosomes), but each spermatid receives 23 chromosomes. The genes in each spermatid are only one half of the genetic characteristics of the father, whereas the other half of the fetal genes are derived from the oocyte provided by the mother. The entire period of spermatogenesis, from spermatogonia to spermatozoa, takes 74 days. Sperm The tail of the sperm or *flagellum,* has three major components: \(1) a central skeleton of 11 microtubules, the *axoneme* \(2) a thin cell membrane \(3) a collection of mitochondria surrounding the axoneme in the proximal portion of the tail or *body of the tail*. It is the flagellar movement what provides motility for the sperm, due to the rhythmical longitudinal sliding motion between the anterior and posterior tubules of the axoneme. Maturation of the sperm in the Epydidimi Sperm formed in the seminiferous tubules goes to the *epididymis,* a 6-meter-long tubule where they spend several days. Sperm in the seminiferous tubules and in the early portions of the epididymis are nonmotile, nonfertile. 18 to 24 hours later, sperm develop the *capability of motility,* in spite of several inhibitory proteins in the epididymal fluid preventing a complete motility. Storage of sperm in the testes 120 million sperm can be formed by the two testes of the human adult each day, most are stored in the vas deferens, where they can remain fertile for at least a month. In the vas deferens, they are kept in an inactive state by multiple inhibitory substances in the secretions of the ducts. But in periods of high sexual activity, storage may be no longer than a few days. After ejaculation, the sperm become motile, and they also become capable of fertilizing the ovum, it is *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 testosterone, estrogens and other hormones, enzymes, and nutrients that are essential for sperm maturation. Sex chromosomes In each spermatogonium, among the 23 chromosomes can be found one X chromosome, or one Y chromosome*.* In normal conditions, never both. During meiotic division, the Y chromosome goes to one spermatid, and the X chromosome goes to another spermatid*.* The sex of the eventual offspring is determined by which of these two types of sperm fertilizes the ovum. Some hormonal stimulus to spermatogenesis *Testosterone,* secreted by the *Leydig cells* located in the interstitium of the testis, is essential for growth and division of the testicular germinal cells. ***LH**,* secreted by the anterior pituitary gland, **induces secretion of** **testosterone** by the Leydig cells. The functions of Sertoli cells are controlled by ***FSH**,* secreted by the anterior pituitary gland, which **induces** **spermiogenesis**. The Sertoli cells synthetize ca. 60 proteins related with reproduction. The most impor-tant are inhibin, androgen-binding protein, and antimüllerian hormone. Androgen binding protein (ABP) is a glycoprotein with a great affinity to testosterone and dihydrotestosterone. ABP is released under the influence of FSH and testosterone. When androgen binding protein (ABP) bounds testosterone or dihydrotestosterone, both hormones became less lipophilic and they can be in higher concentration in the lumen of the seminiferous tubules, once released that they will attained free. This elevated levels of hormones are able to activate spermatogenesis in the tubules and the maturation of the spermatozoa in the epididymis. Inhibin on Seminiferus tubules activity When sperm is not produced, secretion of FSH increases. If there is too much spermatogenesis, secretion of FSH decreases The hypothesis for this feedback is that the Sertoli cells synthetize *inhibin,* a hormone that inhibits the secretion of FSH and possibly also the secretion of GnRH. Inhibin is a glycoprotein of 10-30 Kdal, that has been isolated from cultured Sertoli cells. Inhibin has a potent inhibitory feedback effect on the anterior pituitary gland that produces a negative feedback for control of spermatogenesis, and also has a negative feedback mechanism for control of testosterone secretion. Some hormonal stimulus to spermatogenesis Inhibin is a glycoprotein that inhibits the secretion of FSH. Inhibin is released in varying amounts in concert with testosterone. ***Estrogens**,* produced by the Sertoli cells stimulate FSH in low concentrations inducing spermiogenesis, but in high concentrations causes infertility due to the effect in Sertoli cells**.** *Growth hormone* and *thyroid hormones* control metabolic functions of the testes. **Growth** **hormone promotes early division** **of the spermatogonia** themselves; in its absence, spermatogenesis is severely deficient causing infertility. Physiology of the mature sperm The motile, fertile sperm released by ejaculation are capable of flagellated movement through the fluid medium at velocities of 1 to 4 mm/min. This activity is enhanced in a slightly alkaline medium, as exists in the ejaculated semen, but it is greatly depressed in a mildly acidic medium. A strong acidic medium can cause rapid death of sperm. The activity of sperm increases with increasing temperature, but also does the rate of metabolism, and the life of the sperm is shortened. Although sperm can live for many weeks in the testes, life expectancy in the female genital tract is only 1 to 2 days. Function of the seminal vesicles Each seminal vesicle has a secretory epithelium that secretes a mucoid material containing *fructose, citric* *acid,* other nutrient and *prostaglandins* and *fibrinogen.* During ejaculation, each seminal vesicle empties its contents into the ejaculatory duct shortly after the vas deferens empties the sperm, in order to provide nutrients until one of the sperm fertilizes the ovum. Prostaglandins seems to help fertilization: \(1) **by reacting with the female cervical mucus** to make it more receptive to sperm movement \(2) by **possibly causing reverse peristaltic contractions in the uterus and fallopian tubes** to move the sperm toward the ovaries. Some sperm arrive to the upper ends of the fallopian tubes within 5 minutes. \(3) **stimulates the sperm motility** Function of the prostatic gland The prostate gland secretes a fluid that contains calcium, citrate ion, phosphate ion, a clotting enzyme, and a profibrinolysin by contraction of the capsule of the prostate gland simultaneously with the contractions of the vas deferens. The prostatic fluid is more alkaline, neutralizing the acidity of the fluid of the vas deferens, rich in citric acid and metabolic end products of the sperm, helping fertilization of the ovum. The vaginal secretions are acidic to prevent infections (pH of 3.5 to 4.0). Sperm do not become optimally motile until the surrounding pH is about 6.0 to 6.5, then the slightly alkaline prostatic fluid helps to neutralize the acidity of the other seminal fluids and thus enhances the motility and fertility of the sperm. Semen Semen contains the fluid and sperm from the vas deferens ( 10 %), fluid from the seminal vesicles (60 %), fluid from the prostate gland (30 %), and small amounts of fluid from the mucous glands, as the bulbourethral glands. Thus, the bulk of the semen is seminal vesicle fluid, which is the last to be ejaculated and serves to wash the sperm through the ejaculatory duct and urethra. Testosterone and GnRH Testosterone inhibites anterior pituitary secretion of LH, mainly from the decrease of the secretion of GnRH, that produces a decrease in secretion of both LH and FSH by the anterior pituitary. Thus, the testosterone levels are automatically regulated. Regulation of Spermatogenesis FSH binds to FSH receptors in the Sertoli cells in the seminiferous tubules, and it makes them to grow and secrete various spermatogenic substances. Testosterone and dihydrotestosterone diffusing into the seminiferous tubules from the Leydig cells in the interstitial spaces have a strong tropic effect on spermatogenesis. Thus, **to initiate spermatogenesis, both FSH and testosterone are necessary**.