Spermatozoa differentiation occurs in the
seminiferous tubules
, located in the testis (where the temperature is approximately 2ºC below body temperature).
Leydig cells, which synthesize and release testosterone in response to LH liberated by the pituitary gland, lie between seminiferous tubules. The walls of the seminiferous tubules are composed by
developing gametes and Sertoli cells. Sertoli cells are bound to each other through
tight junctions
, and form a ring between the basal membrane of the tubule and its lumen. They act as a physico-chemical barrier which prevents the entrace of several plasmatic substances into the tubule lumen, as well as retaining the luminal fluid, thereby ensuring and appropriate environment for gamete development and tubule differentiation. The luminal fluid contains large amounts of an androgen-binding protein (secreted by the Sertoli cells) which binds testosterone and allows its accumulation in the tubule lumen.
In response to testosterone secreted by the Leydig cells and to FSH liberated by the pituitary gland, Sertoli cells produce a large variety of cemical messengers that stimulate spermatozoa proliferation and differetntiation. Speramtozoa mature from specialized cells - spermatogonia. Throughout adult life, these cells divide continually, and at each moment only a fraction of these cells undergoes differentiation. The cells arising from the last round of mitosis and differentiation are now ready to start meiosis, and are called
primary spermatocytes
. After growth, the first meiotic division occurs, yielding two
secondary spermatocytes, each carrying 23 chromosomes. Upon undergoing the second meiotic division, secondary spermatocytes become spermatids, which after maturing become spermatozoa
Besides the aforementioned roles, Sertoli cells (under the control of both FSH and testosterone) secrete
inhibin
, a hormona which acts on the anterior pituitary and inhibits FSH secretion. In large amounts, testosterone inhibits LH release by the pituitary, as well as secretion of
GnRH
by the hypothalamus.
Apart from its effect on the seminiferous tubules, testosterone is also responsible for the development of male secondary sexual characters, differentiation and maintenance of the accessory reproductive organs, and it stimulates protein anabolism, bone growth, epiphyseal closure and erythropietin secretion by the kidneys.
Oogenesis
At birth, the ovaries contain about 4 million
primary oocytes
, produced during fetal development from multiplying
oogonia
. The first meiotic division of these primary oocytes begins already during the fetal development, but a state of
meiotic arrest immediately ensues. Meiotic arrest continues until puberty. At that time, some of these primary oocytes continue their meiotic division, but most will eventually degenerate in a process dubbed atresis.
Oocytes are found in folicles. Initially, folicles contain only the oocyte, surrounded by a cell layer called granulosa. As the folicle develops, the oocyte enlarges, granulosa multiplies, and eventually the granulosa layer closest to the oocyte differentiates and forms the zona pellucida. Granulosa cells secrete estrogen, small amounts of progesterone (just before ovulation) and inhibin. They also secrete chemical factors that keep the oocyte in meiotic arrest.
Further folicle growth prompts the surrounding tissue to differentiate into theca, which stimulates estrogen secretion by the granulosa cells. Afterwards, a liquid-filled cavity (antrum) forms inside the follicle, surrounding the oocyte.
Additional follicle development depends on stimulation by the follicle-stimulating hormone (FSH). However before puberty FSh concentration is too low for that to happen.
Each menstrual cycle is started by an increase in FSH secretion by the hypophysis. This leads to the development of 10 to 25 antral and pre-antral. FSH acts on the granulosa and stimulates its proliferation and estrogen secretion. Estrogen is produced from androgens secreted by theca under LH stimulation, and further stimulates granulosa cells. FSH is necessary to prevent follicle atresis, and as FSH levels begin to decrease (within 7 days), a selection occurs : only the follicle with higher sensitivity to FSH (the "dominant" follicle) can survive with low FHS levels and keeps developing, while the other follicles begin atresis. Then, as follicle development continues, granulosa cells become sensitive to LH. At that time, the amounts of estrogen secreted by the dominant follicle become high enough to increase its plasma concentration. These moderately high estrogen levels cause a decrease in GnRH secretion by the hypothalamus and in FSH and LH release from the hypophysis ( negative feedback
). FSH levels decrease more that those of LH, since FSH secretion is also inhibited by the inhibin secreted by the granulosa cells.
When estrogen levels increase a lot, the opposite occurs: a stimulating effect of estrogen on LH release (
positive feedback). This mid-cycle LH surge induces ovulation: the primary oocyte completes the first meiotic division, the antrum enlarges, granulosa cells start secreting progesterona and decreasing estrogen release, and the rupture of the follicle membrane begins, leading to oocyte liberation. The ruptured follicle then becomes the corpus luteum, which releases progesteron and estrogen. In the presence of estrogen, high amounts of progesteron lead to a decreased GnRH secretion, and therefore to diminished FSH and LH levels. In the absence of gonadotropins, the corpus luteum degenerates leading to decreases of progesterone and estrogen. When the levels of these hormones become too low (usually about 14 days after ovulation), hypothalamus secretes GnRH, and the cycle begins anew.
In the first phase of the cycle, the uterus lining (the endometrium) proliferates under the influence of estrogen, which also stimulates the growth of the underlying smooth muscle. After ovulation, progesteron acts on the endometrium and this turns it into a secreting tissue: its glands fill with glycogen, its blood vessels multiply and enzymes accumulate in the connective tissue. These changes are vital for embryo nidation. Progesterone also inhibits uterine contractions, thereby preventing the embryo from being lost before nidation. Absent progesteron, the endometrium thins and menstruation occurs. Embryo implantation prevents menstruation because in secretes
coryonic gonadotropin
(hCG. This hormone prevents the degeneration of the corpus luteum, and therefore preogesterone and estrogen secretion continues even in the absence of LH.
During pregnancy, the uterus muscles (myometrium) are somewhat disconnected and the uterus cervix is closed by a mucus plug. IN the final weeks of pregnancy, very high levels of estrogen prompt myometium cells to synthesize connexia, a protein that forms gap junctions between the muscle cells and enables them to contract in a co-ordinate fashion. At the same time, the cervix becomes softer and more flexible, due to enzymatic degradation of its collagen fibers. Estrogen also induces the synthesis of
oxytocin receptors by the myometrium cells, so that the response to this hormone (which stimulates uterine smooth muscle contraction) during parturition will be effective.
