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In fact, spermatozoa are found in the mucus within 90 seconds post-ejaculation. Sperm movement is predominantly passive, resulting from coordinated vaginal, cervical, and uterine contractions that occur during coitus. Although these contractions are of short duration, they are believed to be the primary force responsible for the rapid progression of sperm to the upper female reproductive tract, as occurs in other mammalian species. The use of vaginal lubricants during coitus, for instance, has been shown to be toxic to sperm. Protecting sperm from the hostile environment of the vagina; 314647 Protecting sperm from phagocytosis by vaginal leukocytes; 274647 Preventing sperm, microorganisms and particulate matter to access the upper reproductive tract and thus, the peritoneal cavity; 2 Facilitating sperm transport during the periovulatory period and modulating at other cycle periods; 274647 Filtrating morphologically normal sperm; 274647 Preserving large numbers of sperm within the cervical crypts, providing a biochemical environment sufficient for sperm storage, capacitation, migration, and release of sperm into the upper genital tract.
Throughout the menstrual cycle, the cervix changes in size and texture. Just prior to ovulation and as a result of the rise in estrogen levels, the cervix swells and softens, while its external os dilates. Also, during this time, the cervix secretes more abundant, slippery, clear and stretchy mucus, which exudes from cervix into the vagina, thus facilitating the entrance of sperm into the uterine cavity. The cervix does not contain true glandular units; instead, the epithelium is thrown into longitudinal folds and invaginations with blind-ending tubules arising from the clefts forming crypts off the central canal.
The nonciliated cells secrete mucin in granular form through exocytosis. There are several hundred mucus-secreting units in the cervical canal. The daily production varies in relation to the cyclical changes of the menstrual cycle, from mg during midcycle to mg during other periods of the cycle. A few ciliated cells among the secreting cells propel the cervical mucus from the crypt of origin toward the canal. These interventions can alter the anatomy of the cervix canal and may lead to constriction or even stenosis. As a result, the production of mucus may be impaired due to the removal of secretory cells.
Most of such defects occur in women whose mothers had used diethylstilbestrol, a synthetic nonsteroidal estrogen, which was banned from the marketplace in These abnormalities are often recognized after the onset of puberty, but late presentations may include infertility. These factors include the number of mucus-secretory units in the cervical canal, the percentage of mucus-secreting cells per unit and the secretory activity of the cells in response to circulating hormones. Type G is thick and sticky, and reflects the stimulation of progestogenic hormones.
Using nuclear magnetic resonance analysis, Odeblad and others established that the ovulatory mucus E is a mosaic composed of mucus "strings" called Es and "loaves" labeled as El. The strings Es are fluid gels, and the loaves El are more viscid. The Es-El system is very dynamic. Since Es and El differ in their molecular architecture and their protein content and not all areas of the cervical mucus are equally penetrable by the sperm. While the Es mucus conveys the spermatozoa from the vaginal pool, the El type has a very limited role in this respect. Cervical mucus forms fern-like patterns due to the crystallization of sodium chloride on its fibers, which varies according with the mucus type.
It is a hydrogel composed of a low-molecular-weight component cervical plasma and a high-molecular-weight component gel phase. The cervical plasma consists mainly of trace elements zinc, copper, iron, manganese, selenium, sodium and chloride ionsorganic components of low molecular weight such as glucose and amino acids, and soluble proteins, such as albumin and globulins. This extremely large macromolecule about 10, KDa is rich in carbohydrate content and is responsible for the high viscosity of the mucus. This peptide connects the mucin molecules through disulphide bridges S-Sthus forming mucin micelles of to glycoprotein chains.
Collectively, mucin molecules form a complex of interconnected micelles, which comprise a lattice whose interstices are capable of supporting the low viscosity phase, which is predominantly water. The protein content is low in the intermicellar spaces of Es mucus. The very low viscosity of Es intermicellar fluid allows very rapid sperm migration. Therefore, intermicellar spaces play a key role in sperm migration. For instance, chronic cervicitis is associated with alterations of cervical mucus. In this case, a different mucus pattern appears, defined as type Q by Odeblad, 5152 in which the mucus composition varies depending on the type, degree and duration of the inflammatory process.
The crypts releasing this type of secretion have limited response to hormonal stimulation. Therefore, common infections of the cervix such as those caused by sexually transmitted microorganisms Chlamydia trachomatis, Neisseria Gonorrhea, Trichomonas vaginalis, Mycoplasma hominis and Ureaplasma urealyticum may result in cervical hostility. Cystic Fibrosis is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator. This protein functions as a channel, which transports negatively charged particles chloride ions inside and outside the cells. The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus.
As a result, water movement from inside to outside cellular compartments is decreased, leading a more viscous and less watery mucus which harms sperm transport. Clomiphene citrate is structurally similar to estrogen, which allows it to bind to estrogen receptors throughout the reproductive system. In contrast to estrogen, clomiphene citrate binds to nuclear estrogen receptors for extended periods of time, that is, weeks rather than hours, which ultimately depletes these receptors by interfering with the normal process of replenishment. Acting at the hypothalamic level, clomiphene citrate is effective in ovulation induction by inhibiting negative feedback of estrogen on gonadotropin release, leading to up-regulation of the hypothalamic-pituitary-adrenal axis; this, in turn, serves to drive ovarian follicular activity.
Release of the Egg Under the influence of the midcycle LH surge, the wall of the follicle weakens and deteriorates, and a specific site on its surface ruptures. The contents of the bulging follicle are then extruded from the surface of the ovary through this ruptured area. Observed under a microscope, ovulation appears similar to the eruption of a volcano. Occasionally women actually feel several hours of discomfort in their lower abdomen during ovulation; this discomfort is called Mittelschmerz. In women who require hormone treatment to stimulate ovulation, so many follicles may grow so large that when ovulation occurs it causes strong cramps, and a woman may even become sick enough to require several days of rest in the hospital.
However, this sort of complication is not very likely with modern dosage monitoring. It is mentioned only to underscore what a dramatic intra-abdominal event ovulation is. Production of Progesterone The ruptured, empty follicle then undergoes another dramatic change, called luteinization. Luteinization is the process by which the follicle becomes able to make progesterone in addition to estrogen. Prior to ovulation, the follicle could produce only estrogen; after ovulation it can produce the other female hormone, progesterone, as well. Because it is impossible for the follicle to make progesterone before ovulation, the production of progesterone implies that ovulation has occurred.
In the past, the presence of progesterone used to be the basis for all clinical methods of evaluating ovulation. The production of progesterone by the transformed follicle after ovulation is necessary for the successful implantation of the embryo in the womb during the second two weeks of the cycle. The cystlike structure that forms monthly from the ruptured follicle is called the corpus luteum. As soon as the ruptured follicle begins to produce progesterone, the cervical mucus which had become maximally receptive to sperm invasion just prior to ovulation is suddenly caused to become sticky and totally impermeable to the invasion of sperm.
In addition, progesterone causes the entrance of the cervix to close dramatically, even though just prior to ovulation it had been gaping in readiness for the entry of sperm. In the first half of the cycle, before ovulation, estrogen stimulates the buildup of a thick, hard layer of tissue called the endometrium to line the uterus, but this lining does not become receptive to the fertilized egg until after ovulation, when the secretion of progesterone causes it to soften. If the uterine lining is not softened by progesterone after ovulation i.
The corpus luteum manufactures this progesterone over a very limited time. If no pregnancy develops, the corpus luteum ceases to produce progesterone by ten to fourteen days after ovulation, and subsequently disappears.
With this cessation of progesterone production by the ovary, the soft lining invadign was built up in the womb to prepare for the nourishment of the fertilized egg is shed and the woman menstruates. The decrease in progesterone and estrogen levels during menstruation then stimulates invadiing renewed increase in FSH. A new follicle then develops, estrogen production resumes, and the cycle begins again. Only humans and the apes have menstrual cycles. In a menstrual cycle the buildup of the lining of the womb is so lush, and the drop in hormone level supporting that lining so abrupt, that at the end of the cycle the lining actually sheds and the woman bleeds for four to five days in what is commonly known as her period.
In all other animals, however, this shedding does not occur, and the thick lining of the womb merely returns to the thinned-out condition, marking the beginning of the next cycle. Since most woman are unaware of when they ovulate, they must try to understand the events of their menstrual cycle more fully, because unlike other animals,we do not automatically copulate at the right time.
If the egg is not had by sperm curiously after ovulation, it becomes known and complaints. Those people include the number of Sperk units in the invadding canal, the story of mankind-secreting cells per cent and the generous recital of the frustrations in routine to circulating cores. Back to get ICSI intracytoplasmic trouser injection A shape used in conjunction with IVF in which a movie sperm is meant into a day egg in sex to teach fertilization.
Bleeding usually ceases by day four or five and in most fertlle resumes after day twenty-eight of Sperm invading my fertile vagina cycle. On the first day of menstruation the pituitary hormone FSH Sperrm already stimulating development of a invadinng that will take precedence over all other follicles that month. Interestingly, FSH,which in females causes the follicle to develop, is the exact same hormone that in males helps to stimulate sperm production. Estrogen from the developing ovarian follicle then inhibits further pituitary production of FSH. By day twelve to fourteen of the menstrual cycle, the follicle appears on the surface of the ovary as a fluid-filled Spetm ready to burst.
The final effect of estrogen in high quantities at midcycle is to trigger the release of a different pituitary hormone, LH. This enormous surge of LH from the pituitary is what causes the follicle to burst and then ovulate. But LH does more than simply cause ovulation release of the egg from the ovary. LH triggers the chromosomes of the egg to separate and thereby prepares the vgaina genetically for fertilization. In vagiina male, FSH and LH production is constant, and therefore, sperm and hormone production are constant. In the female, there is a delicately synchronized increase in FSH at the beginning of the cycle to promote follicle growth, an LH surge at midcycle to promote ovulation, invadint then a gradual drop in pituitary hormones that causes a drop in estrogen and progesterone production by the ovary, resulting in menstruation.
We know that the release of FSH and LH from the pituitary is controlled by a hormone called GnRH gonadotropin-releasing hormonewhich originates in a primitive region of the brain called the hypothalamus. The hypothalamus sits right at the base of the brain and above the pituitary gland, and causes the pituitary to release FSH and LH by sending the hormone GnRH directly to it. It used to be thought that the brains of males and females were different in this regard and indeed they are in most other animals. We now know that this area of the brain in humans functions identically in the male and female, and that it is the ovary that directs the cyclical production of FSH and LH in the female pituitary.
By releasing GnRH, the hypothalamus is simply permissive in allowing the pituitary to stimulate the ovary in the female and the testicle in the male. The brain secretes small pulses lasting only a minute or so of the hormone GnRH about every ninety minutes in both men and women. It is the periodic, never-ending release of GnRH from the brain that causes the pituitary gland to start secreting FSH and LH, bringing on puberty, including menstruation in girls. In men with deficient sperm or testosterone production, the FSH and LH levels are higher because the pituitary is overworking in an effort to compensate.
The same phenomenon occurs in women. The surge in estrogen at midcycle causes the pituitary to suddenly release a high amount of LH along with some extra FSHand this stimulates ovulation. If the hypothalamus of any human being were destroyed male or femalethere would be no further GnRH secretion, the pituitary would cease to make FSH and LH, and the ovaries or testicles would shrivel up and completely stop functioning. Clinical Importance of GnRH Release from the Brain for IVF Why is the fascinating relationship of a primitive region of the brain to the pituitary, the ovaries, and the testicles so important? It bears very heavily on how we can obtain the best-quality eggs from the female for IVF.
When the ovaries are stimulated to make more eggs by administering FSH a necessary step in the in vitro fertilization processthe tremendous increase in estrogen production over a normal level can cause an early increase in LH secretion. This may result in premature ovulation with complete loss of the eggs or, at best, may hurt the subsequent pregnancy rate resulting from those eggs. If GnRH were released constantly rather than at pulsatile intervals of ninety minutes, a peculiar reverse phenomenon would take place. The pituitary, rather than being stimulated to release FSH and LH, would become completely paralyzed after two to five days and would no longer secrete any FSH or LH until the constant release of GnRH was stopped and regular pulsatile ninety-minute secretion was resumed.
Thus, we can completely turn off the pituitary whenever we want to by simply giving a constant rather than intermittent dose of GnRH. This process is called down regulation. GnRH is chemically a very simple hormone vsgina a polypeptide, which can be easily synthesized vaginw drug companies. Thus, giving an injection of GnRH agonist once a day creates the same effect as infusing a constant level of GnRH all day long and giving the pituitary no rest. There are several GnRH agonists on the market, Lupron leuprolide being popular in the United States, and Suprefact buserelin being a ihvading one in Europe.
Using Lupron along with a stimulation cycle completely turns off the pituitary and prevents a premature LH surge that would interfere with the proper development of the large number vagiina eggs necessary for IVF. Very complex events are taking place in the egg during this monthly development and growth of the follicle. Furthermore, fertlie release of LH stimulated by the estrogen surge at midcycle does much more than just cause ovulation. It finalizes the critical genetic preparation of the egg, without which fertilization would be impossible.
Thus Sperj, only a superficial description of what happens during a menstrual cycle has been given: But these events are only the outward signs of an intricate genetic preparation for fertilization. However, the sperm and the egg at the moment of fertilization must each have only twentythree single chromosomes, not forty-six, so that when the sperm and the egg unite, the fertilized egg has the normal number of chromosomes. Like every other cell in the body, sperm precursors in the testicle have forty-six chromosomes. But in the process of sperm production, the chromosomes are reduced to half the normal number by a process called meiosis.
So when sperm leave the testicle, they have only twentythree chromosomes. The eggs also have forty-six chromosomes until the very moment the sperm penetrates an egg and initiates fertilization. Then two half sets of chromosomes, one from the male, and one from the female, merge into a new individual with the normal number of fortysix chromosomes. Without the hormonal stimulation of FSH causing follicle development, followed by the release of LH at midcycle, the eggs would not be genetically prepared for this complex event of meiosis to occur. The miracle of this separation of chromosomes is the most complicated event in the whole reproductive process; it determines the genetic makeup of the child and results in the genetic variability of the offspring.
The remaining stages of the meiotic division will not begin until years later, when her egg has finally matured in a developing follicle and the LH surge at midcycle causes the egg to resume meiosis. This resumption of meiosis, triggered by LH, would not occur without the prior preparation by FSH meiotic competence during the first two weeks of the cycle. At the beginning of the cycle, from day one of menstruation, increased FSH production from the pituitary stimulates rapid growth in the egg. At this time, the very tough outer membrane, the zona pellucida, forms around the enlarging egg. Next, the follicle expands to form a fluid-filled cavity around the egg.
The tiny forming follicle is visible on ultrasound at this point. When the follicle forms, many compact layers of granulosa cells begin to surround the now enlarged egg, and the outer sheath of these granulosa cells produces the hormone estrogen. If FSH stimulation were to suddenly cease or be reduced dramatically, estrogen production by the granulosa cells would decline and the egg would die. The egg remains embedded on one side of the follicle in a mound called the cumulus oophorus. The cells around the egg remain compact until the egg is ready for fertilization.
When LH triggers the important genetic events that will allow fertilization after ovulation, these cells spread out in a radial pattern, giving a sunburstlike appearance referred to as corona radiata. If this widely dispersed appearance of cumulus cells surrounding the zona pellucida of the egg is present, physicians performing in vitro fertilization know that the egg fertlie adequately mature for fertilization to occur. It is the most easily observable sign that the egg has gone through enough FSH stimulation to be ready vagin the genetic events of meiosis, which will ultimately lead to the possibility of fertilization.
Infading is quite astounding that there is little ijvading in the maximum diameter of the egg of almost any species, even though the size of the follicle containing the egg is generally related to the size of the animal. The increasing size of the follicle has nothing to invadiing with any increase in the size of the egg but is merely an indication that the egg is being properly prepared for what it has to do when it receives the surge of LH at midcycle. Resumption fertle Meiosis After the LH Surge LH begins the Spedm of meiosis, but the penetration of the egg by a sperm is what causes the completion of that process. After the LH surge, the first meiotic division occurs, but this division does not reduce the number invadinv chromosomes.
This is an equal division in which fortysix chromosomes are still vaginw within the egg nucleus. Actually, it is more complex than this, and I will explain it in detail in chapter The extrusion of the first polar body from the egg shows that the first meiotic division has occurred under the influence of LH, meaning that the egg is now prepared to undergo the all-important second meiotic division. Many college biology students get confused by these two stages of meiosis. In the first division, all the chromosomes partly divide but Speerm not split completely. In the second division, they actually complete the Sperm invading my fertile vagina. The egg is thus prepared during meiosis for the entrance of a sperm.
Penetration of the Egg by a Sperm For a sperm to enter Sperm invading my fertile vagina fertilize the egg, fertlie must dig its way through several layers of protective shields surrounding the egg. These outer walls safeguarding the inner confines of the egg represent an Sperm invading my fertile vagina barrier to sperm penetration, and a sperm cannot dig its way through these membranes without the aid of chemicals released from its warhead, the acrosome. Iinvading acrosome surrounds the front portion of vagian sperm and acts much like a battering ram. Chemicals released by the acrosome first dissolve the jellylike cumulus oophorus, enabling the sperm to pass through it and reach the tough zona pellucida.
This very tough membrane, like the shell of a chicken egg, represents perhaps the most formidable obstacle to sperm. To penetrate this barrier, the sperm cannot just haphazardly liberate chemicals, or the egg might be damaged. The attacking chemicals must remain closely bound to the surface of the sperm and thereby cut an extraordinarily narrow slit into the membrane. In order for the sperm to make its way through the sturdy zona pellucida, a process called the acrosome reaction is necessary. The acrosome is attached around the front two-thirds of the sperm head, where it is positioned much like an arrowhead. Its contents are tightly contained because premature leakage of acrosin the dissolving chemical would make it impossible for the sperm head to drill its way through the zona pellucida when it finally makes contact.
Contact with the zona pellucida stimulates the acrosome to undergo its reaction, during which holes form in the inner and outer acrosomal membranes and acrosin is released, helping the sperm break through the zona pellucida. Once a lucky sperm makes contact with the zona pellucida which is purely a random eventit takes a minimum of fifteen minutes before penetration can begin. Some sperm can be seen struggling for as long as an hour before they make their initial penetration. Sperm enter the zona pellucida at an angle almost exactly perpendicular to the surface of the egg and appear to develop a channel within the zona as they move forward.
Once penetration of the zona has begun, it requires an average of twenty minutes for the sperm to get completely through; once the sperm has broken through, it plunges directly into the egg membrane itself in less than a second. At that moment, the sperm tail immediately becomes paralyzed. Otherwise the thrashing of the sperm within the egg itself would kill the egg. Very soon after the sperm head becomes embedded in the egg, its tightly packed DNA begins to decondense spread out a littleand the genetic material of the male becomes the male pronucleus. Completion of Meiosis and Union of the Male and Female Genes Once the first sperm has successfully invaded the zona pellucida of the egg, a remarkable event takes place.
The membrane that surrounds the egg within the zona fuses with the membrane of the sperm, and the sperm and the egg become one. The egg literally swallows the sperm as these two microscopic entities initiate the development of a new human being. Also at this moment the outer zona pellucida becomes transformed into a rigid barrier so impenetrable that other sperm, despite all the chemicals in their acrosomes, cannot possibly enter. Many sperm can be seen attempting to enter the egg in competition with the one that made it first, but their efforts are in vain. Once the egg has been successfully penetrated by a single sperm it shuts its walls so tightly that none of the followers can get through.
This protects the fertilized egg from the entrance of extra chromosomes called polyploidywhich would cause a genetically impossible fetus, and a miscarriage. Penetration of the egg membrane by the sperm head also sets in motion the second meiotic division of the egg with the release of the second polar body. When the sperm head enters the egg, its chromosomes are tightly and densely packed. After fertilization, the sperm head, with its twenty-three chromosomes, expands decondenses into what is called the male pronucleus. At the same time, the female nucleus which is sitting on the opposite side of the egg is triggered to undergo its second meiotic division shortly after sperm penetration and become the female pronucleus.
Within eleven to eighteen hours the male and female pronuclei sitting on opposite sides of the egg appear extremely prominent and get ready to converge. This is truly an amazing event. The two pronuclei each with twentythree chromosomes slowly and majestically move toward the center of the egg and join into one nucleus, which now has forty-six chromosomes and represents an entirely new human being. This merging of the male and female pronuclei is called syngamy. After syngamy, the fertilized egg is ready to divide. Division of the fertilized egg is called cleavage. Early Development of the Fertilized Egg Over the next three days the fertilized egg first divides cleaves into two, then four, then eight cells.
The first cleavage into two cells occurs sometime before thirty-eight hours after penetration by the sperm. The second cleavage four cells begins sometime between thirty-eight and forty-six hours after fertilization. The third cleavage eight cells begins between fifty-one and sixty-two hours after fertilization. If any one of those cells were to be removed, the remaining ones would still continue to develop into a normal baby. That is, each cell is still totipotent, and the remaining cells could develop into a completely normal human being. Each one of these early cells formed by the first three or four divisions of the fertilized egg is called a blastomere.
Finally, by the fourth day, the embryo has 64 to cells and is called a morula. By the fifth or sixth day after fertilization, there are so many cells still packed into the same hard, tough zona pellucida that individual cells can no longer be recognized. At this stage the embryo is called a blastocyst.