Fertilization - Embryology
Keywords: embryo transport, Fallopian tube, fertilization, sperm migration, zygote. RBMOnline - Vol 4. No 2. Anatomical relationships of the rat oviduct and the can result in pregnancy if it occurs on the day of ovulation or during any of the 5. The isthmus is thought to regulate sperm and embryo transport. . partner for Izumo1 and named it “Juno” after the Roman goddess of marriage and fertility. Monoygotic Twinning. 14 References; 15 Glossary Links The first week of human development begins with fertilization of the egg by sperm forming the first cell, the zygote. Cell division leads to a ball of . Event, Ovulation, fertilization, First cell division, Morula, Early blastocyst, Late blastocyst. Hatching.
The tubule thus formed establishes continuity between the egg and the spermatozoon and provides a way for the spermatozoal nucleus to reach the interior of the egg. Other spermatozoal structures that may be carried within the egg include the midpiece and part of the tail; the spermatozoal plasma membrane and the acrosomal membrane, however, do not reach the interior of the egg. In fact, whole spermatozoa injected into unfertilized eggs cannot elicit the activation reaction or merge with the egg nucleus.
As the spermatozoal nucleus is drawn within the egg, the spermatozoal plasma membrane breaks down; at the end of the process, the continuity of the egg plasma membrane is re-established. This description of the process of sperm-egg association, first documented for the acorn worm Saccoglossus phylum Enteropneustagenerally applies to most eggs studied thus far.
During their passage through the female genital tract of mammals, spermatozoa undergo physiological change, called capacitation, which is a prerequisite for their participation in fertilization; they are able to undergo the acrosome reaction, traverse the egg envelopes, and reach the interior of the egg. Dispersal of cells in the outer egg envelope corona radiata is caused by the action of an enzyme hyaluronidase that breaks down a substance hyaluronic acid binding corona radiata cells together.
The enzyme may be contained in the acrosome and released as a result of the acrosome reaction, during passage of the spermatozoon through the corona radiata. The reaction is well advanced by the time a spermatozoon contacts the thick coat surrounding the egg itself zona pellucida. Association of a mammalian spermatozoon with the egg surface occurs along the lateral surface of the spermatozoon, rather than at the tip as in other animals, so that the spermatozoon lies flat on the egg surface.
Several points of fusion occur between the plasma membranes of the two gametes i. In general, the biochemistry of the zona pellucida of one species differs from that of another, and thus it only matches up and binds with sperm of the appropriate species.
For example, among the echinoderms, solutions of the jelly coat clump, or agglutinate, only spermatozoa of their own species. In both echinoderms and amphibians, however, slight damage to an egg surface makes fertilization possible with spermatozoa of different species heterologous fertilization ; this procedure has been used to obtain certain hybrid larvae.
In addition, binding between sperm and egg of different species may occur when the zona pellucida of the egg is removed. The eggs of ascidians, or sea squirtsmembers of the chordate subphylum Tunicataare covered with a thick membrane called a chorion.
The space between the chorion and the egg is filled with cells called test cells. The gametes of ascidians, which have both male and female reproductive organs in one animal, mature at the same time, yet self-fertilization does not occur. If the chorion and the test cells are removed, however, not only is fertilization with spermatozoa of different species possible, but self-fertilization also can occur. Prevention of polyspermy Most animal eggs are monospermic; i.
In some eggs, protection against the penetration of the egg by more than one spermatozoon polyspermy is due to some property of the egg surface; in others, however, the egg envelopes are responsible. The ability of some eggs to develop a polyspermy-preventing reaction depends on a molecular rearrangement of the egg surface that occurs during egg maturation oogenesis.
Although immature sea urchin eggs have the ability to associate with spermatozoa, they also allow multiple penetration; i. Since the mature eggs of most animals are fertilized before completion of meiosis and are able to develop a polyspermy-preventing reaction, specific properties of the egg surface must have differentiated by the time meiosis stops, which is when the egg is ready to be fertilized.
In some mammalian eggs defense against polyspermy depends on properties of the zona pellucida; i. In other mammals, however, the zona reaction either does not take place or is weak, as indicated by the presence of numerous spermatozoa in the space between the zona and egg surface.
In such cases the polyspermy-preventing reaction resides in the egg surface. The link between the centromeres of sister chromatids is broken at anaphase II, and sister chromatids segregate to opposite poles. Cytokinesis then follows, giving rise to haploid daughter cells.
Regulation of Oocyte Meiosis Vertebrate oocytes developing eggs have been particularly useful models for research on the cell cycle, in part because of their large size and ease of manipulation in the laboratory. A notable example, discussed earlier in this chapter, is provided by the discovery and subsequent purification of MPF from frog oocytes.
Meiosis of these oocytes, like those of other species, is regulated at two unique points in the cell cycle, and studies of oocyte meiosis have illuminated novel mechanisms of cell cycle control.
The first regulatory point in oocyte meiosis is in the diplotene stage of the first meiotic division Figure Oocytes can remain arrested at this stage for long periods of time—up to 40 to 50 years in humans. During this diplotene arrest, the oocyte chromosomes decondense and are actively transcribed. This transcriptional activity is reflected in the tremendous growth of oocytes during this period.
Frog oocytes are even larger, with diameters of approximately 1 mm. During this period of cell growth, the oocytes accumulate stockpiles of materials, including RNAs and proteinsthat are needed to support early development of the embryo.
As noted earlier in this chapter, early embryonic cell cycles then occur in the absence of cell growth, rapidly dividing the fertilized egg into smaller cells see Figure Meiosis is arrested at the diplotene stage, during which oocytes grow to a large size. Oocytes then resume meiosis in response to hormonal stimulation and complete the first meiotic division, with asymmetric cytokinesis more Oocytes of different species vary as to when meiosis resumes and fertilization takes place.
In some animals, oocytes remain arrested at the diplotene stage until they are fertilized, only then proceeding to complete meiosis. However, the oocytes of most vertebrates including frogs, mice, and humans resume meiosis in response to hormonal stimulation and proceed through meiosis I prior to fertilization. Cell division following meiosis I is asymmetric, resulting in the production of a small polar body and an oocyte that retains its large size. The oocyte then proceeds to enter meiosis II without having re-formed a nucleus or decondensed its chromosomes.
Most vertebrate oocytes are then arrested again at metaphase II, where they remain until fertilization. Like the M phase of somatic cells, the meiosis of oocytes is controlled by MPF. The regulation of MPF during oocyte meiosis, however, displays unique features that are responsible for metaphase II arrest Figure Hormonal stimulation of diplotene -arrested oocytes initially triggers the resumption of meiosis by activating MPF, as at the G2 to M transition of somatic cells. As in mitosisMPF then induces chromosome condensation, nuclear envelope breakdown, and formation of the spindle.
The acrosome reaction is an exocytotic process occurring in the sperm head that is essential for penetration of the zona pellucida and fertilization of the oocyte. The acrosome is a unique organelle, located in the anterior portion of the sperm head analogous to both a lysosome and a regulated secretory vesicle. It exists in a proenzyme form called proacrosin, which is converted to the active form acrosin by changes in acrosomal pH. The binding causes an opening of calcium channels and an influx of calcium and second messengers that result in the acrosome reaction.
Other substances may also induce the acrosome reaction. For example, the addition of periovulatory follicular fluid or progesterone to capacitated spermatozoa stimulates an influx of calcium ions that is coincident with the acrosome reaction.
Week 1 - Embryology
However, other acrosome reaction-stimulating factors e. The zona pellucida plays an important role in species-specific sperm-egg recognition, sperm-egg binding, induction of the acrosome reaction, prevention of polyspermy, and protection of the embryo prior to implantation.
ZP3 is the primary ligand for sperm-zona binding and acrosome reaction induction. A major breakthrough was made in when researchers identified a protein on the surface of the capacitated sperm named Izumo1 after a Japanese marriage shrine.
Sperm that lacked this receptor were unable to fuse with normal eggs. They showed that Juno-deficient eggs were not able to fuse with normal capacitated sperm, which proved that the Juno-Izumo receptor interaction was essential for mammalian fertilization.
Additionally, there is evidence that Juno is undetectable on the oolemma about 40 minutes after fertilization, which suggests that this may be the mechanism for membrane block to polyspermy in mammals.
The majority of current data concerning sperm receptors for zona glycoproteins is restricted to nonhuman mammalian and nonmammalian species. In the human, one of the best described ZP3 receptor candidates is a lectin that binds mannose-containing ligands. Interestingly, both intact zona pellucida and progesterone stimulate tyrosine phosphorylation. The possibility exists that one or more signaling or second-messenger pathways interact to result in the acrosome reaction, and subsequent penetration of the oocyte vestments by the spermatozoon.
In fact, this arrangement could provide sperm with the ability to sense and respond to molecules present in the female reproductive tract that have been shown to initiate the acrosome reaction, such as follicular and oviductal fluids and the cumulus oophorus. After a spermatozoon passes through the zona pellucida, it must contact, bind to, and fuse with the oocyte plasma membrane. As a result of the prior acrosome reaction, new sperm membrane proteins become exposed that are likely to prove integral for sperm-oocyte fusion.Ovulation
Data indicate that sperm-oocyte fusion is initiated by signal transduction processes that involve adhesion molecules on both sperm and oocyte plasma membranes that belong to the family of integrins.
Fibronectin and vitronectin are glycoproteins that contain functional RGD sequences, and they are present on spermatozoa. These data suggest that a possible mechanism for sperm-oocyte adhesion and fusion involves an integrin-vitronectin receptor-ligand interaction. At some point during or after the fusion process, the oocyte is activated by the spermatozoon. Extrusion of the second polar body occurs and cortical granules are released into the perivitelline space. The cortical granules modify zona glycoproteins 2 and 3 on the inner aspect of the zona pellucida, resulting in a loss of their ability to stimulate the acrosome reaction and tight binding, so as to prevent polyspermy.
This latter event occurs before or simultaneously with the resumption of meiosis. Failure of the oocyte to synthesize or release the cortical granules in a timely fashion results in polyspermic fertilization.
Calcium is the main intracellular signal responsible for the initiation of oocyte activation. The mechanism by which sperm induce calcium transients is unknown, but there are data that support essentially two models for sperm-induced oocyte activation.
During this latent period, a soluble sperm-derived factor diffuses from the sperm into the oocyte's cytoplasm and results in oocyte activation. Progesterone secreted by the cumulus cells that surround the oocyte stimulates calcium signals that can control hyperactivation and the acrosomal reaction, however, the signaling mechanism has remained unclear.
Recent research has shown that progesterone activates a sperm-specific calcium channel named CatSper, which is primarily associated with hyperactivation of sperm. CatSper has been shown to be necessary for hyperactivation in mice and several men with infertility have been found to have deletions of the CatSper gene.