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.
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 insulinlike 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 entering 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.
