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Sexual Differentiation And Function


Sexual Differentiation And Function
Sexual differentiation
Gender is determined by the presence of X and Y chromosomes in the genome. Two X chromosomes provide the female genotype, whereas X and Y chromosomes together give a genetic male. Undifferentiated gonads are apparent after about 4–6 weeks of gestation, and both Müllerian ducts, which eventually form the uterus and Fallopian tubes, and Wolffian ducts, which form the vas deferens, epididymis and seminal vesicles, are present. The early gonads secrete steroids just as they do in the adult, and these hormones determine the sexual phenotype. In the absence of the Sry gene on the Y chromosome and thus testosterone, the Müllerian ducts continue to differentiate whilst the Wolffian ducts regress. The development of reproductive organs and brain connectivity therefore defaults to a female pattern which is dependent on the secretion of oestrogens.

The Sry gene is thought to be responsible for the establishment of testicular development and Leydig cells which secrete testosterone. Testosterone stimulates the development of the male genitalia (Fig. 51a) and the organization of neuronal systems in the brain that are involved in sexual function and behaviour. Notably, there is marked growth in the sexually dimorphic nucleus of the medial preoptic area of the hypothalamus and in the spinal nucleus that controls the bulbocavernosus muscle which is involved in ejaculation. Curiously, testosterone has to be converted to oestrogen by brain aromatases to have these effects. The fetal testis also secretes anti- Müllerian hormone (AMH) which causes regression of Müllerian ducts and thus prevents the uterus and Fallopian tube from developing.

Sexual Differentiation And Function

Puberty
Although active before birth, the gonadotrophic axis quickly becomes quiescent after parturition and remains so until the onset of puberty at 8–14 years. The trigger for this remains obscure, but may result from endogenous activation of brain pattern generating circuits that stimulate gonadotrophin-releasing hormone (GnRH) neurones. Body mass, signalled via circulating levels of leptin (Chapter 43) and insu­ lin­like growth factor­1 (IGF­1) (Chapter 46), are important permissive factors in females and undernutrition is associated with failure of the menstrual cycle. Puberty begins when GnRH stimulates cyclic release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary (Chapter 50), first at night and then throughout the day. LH stimulates release of testosterone from Leydig cells in males and follicular oestrogens in females, and FSH the onset of spermatogenesis in males and follicle growth in females; they therefore act synergistically. This is accompanied by the many physical changes associated with the final growth into an adult (Table 51). The appearance of secondary sexual characteristics in the male is thought to be largely stimulated by the testosterone metabolite, dihydrotestosterone. In females, the onset of the cyclic release of LH and thus oestrogens gives rise to the beginning of menstruation (menarche) and the development of the mature female body pattern (Table 51). The end of puberty marks the onset of full sexual maturity and the conclusion of somatic growth (Chapter 47). Figure 51a,b shows the mature male and female reproductive tracts.

Sexual function
Sexual attraction and behaviour in humans are the highly complex result of physiological factors, combined with societal and other psychological influences. The overall level of libido (sexual motivation) is set by the hypothalamus under the influence of higher centres and the hormonal environment. In males, sexual arousal arises from physical stimulation of the genitalia (a spinal reflex) or from psychological stimuli (by pathways descending from the hypothalamus via the brain stem) that activate sacral parasympathetic nerves (Chapter 7). The penis becomes erect as the result of the dilation of blood vessels enter­ ing the corpora cavernosum (the main erectile tissue) and corpus spongiosum (Fig. 51a). The enhanced flow of blood into the cavernous spaces increases tissue pressure and restricts venous drainage, causing a further build­up of pressure to make the penis fully erect. The para­ sympathetic nerves cause vasodilatation by the release of acetylcholine, vasoactive intestinal peptide and, primarily, nitric oxide (NO; Chapter 21). NO increases the manufacture of cyclic guanosine mono- phosphate (cGMP) in blood vessel smooth muscle cells to cause them to relax. Sildenafil (Viagra) inhibits the breakdown of cGMP and thus enhances erectile function. The female sexual response sometimes involves erection of the clitoris, but the main manifestations are relaxation of the smooth muscles of the vagina and an increase in mucous secretions that act as a lubricant. Again, these actions are brought about by the activation of parasympathetic nerves. The combined effects of the male and female sexual responses facilitate entry of the penis into the vagina (intromission). Frictional forces stimulate mechanoreceptors in the glans penis and the clitoris that eventually lead to reflex activation of the sympathetic nerves that causes orgasm. In the male, this involves peristaltic contractions of the epididymis to pump sperm into the urethra, where they are mixed with the secretions of the bulbourethral gland, the seminal vesicle and the prostate gland to form semen. The secretions provide, respectively, lubrication, energy (in the form of the sugar fructose) and an alkaline barrier against the acid conditions normally prevalent in the vagina. They also include high levels of prostaglandins, the arachidonic acid­derived local hormones that stimulate the motility of sperm and of the female tract. Further peristaltic contractions of the urethra, in combination with the action of the bulbocavernosus muscle, emit the semen bolus into the upper end of the vagina (ejaculation). The female orgasm, which may involve the release of pituitary oxytocin elicited by mechanical stimulation of the cervix (Chapter 52), results in rhythmic contractions of the vaginal and uterine muscles that promote the flow of semen into the uterus. Sperm move by means of their own motility and by the beating of cilia on the walls of the uterus, but only a few hundred sperm of the millions released in a single ejaculate will complete the 6­h journey from the vagina to the oviducts.