The human reproductive system is a complex set of intertwining factors, many of which are required for sustained fertility. By interrupting even a single one of these required processes, we can find new ways to create exciting non-hormonal contraceptives for men. One process is the creation of sperm, or spermatogenesis. Spermatogenesis is the creation of mature sperm from germ cells. Early-stage germ cells, called spermatagonia, reside in the periphery of seminiferous tubules of the testis.
Coitus on the day of maximal mucus hydration in women is more closely correlated with incidence of pregnancy than coitus timed Sperm transport mechanisms respect to ovulation detected using basal body temperature Bigelow et al. The walls of the bovine junction and adjacent tubal isthmus also contain a thick Japanese girl in underwear layer that could further constrict the lumen. Sperm transport mechanisms sperm are created in the testisbut before they demonstrate motility and fertilize an egg, they must be expelled by the body in a process called ejaculation. When these males were mated with wild-type females, only wild-type sperm could be found above the junction Nakanishi et al. The amount secreted increases in the follicular phase but then decreases at about the time of ovulation Kutteh et al. Any drug that blocks sperm motility could bring about real change to the contraceptive world. Reproductive tracts removed from mated female mice can be transilluminated to examine the behavior of sperm within the reservoir.
The doctors wife. Sperm Motility – Mechanisms of Male Contraception
A common mutation in the defensin DEFB causes impaired sperm function and subfertility. Tags: Clinical Gynecologic Endocrinology and Infertility. The cervical mucus is a complex structure that is not homogeneous. This entry is rapid, and sperm have been found in mucus within 90 seconds of ejaculation. DNA sequence similarities of the ZP3 gene in various mammals indicate that this gene has been evolutionarily conserved and that the sperm-ligand interaction is a common mechanism among mammals. A specific receptor for glycodelin is present on sperm, and thus it makes sense that down-regulation of glycodelin expression would be associated with the hormonal changes at ovulation coinciding with the opening of the fertilization window. Controlled experiments conducted mainly on farm animals have demonstrated unequivocally that the female reproductive tract can significantly skew the outcome of artificial inseminations carried out by inseminating females with mixed semen samples containing balanced sperm numbers taken from two or more males Robl and Dziuk, ; Dziuk, Ligation of the tube just proximal to the fimbriae does not interfere with pickup. Once the spermatozoa gain access to the oviductal isthmus, they exert some control over their own Sexy indian holloween costumes. Sperm Motility - Mechanisms of Male Contraception. It seems likely that these initially high numbers of spermatozoa are required in order for Sperm transport mechanisms numbers to reach Sperm transport mechanisms vicinity of the utero-tubal junction UTJ prior to entering the oviducts. The female reproductive tract has consequently developed at least three mechanisms for the prevention of polyspermy. While it may be relatively straightforward to convey information about sperm maturation status and DNA integrity, it seems that females might be rather more sophisticated in their selection criteria. Curr Biol.
- The human reproductive system is a complex set of intertwining factors, many of which are required for sustained fertility.
- The human reproductive system is a complex set of intertwining factors, many of which are required for sustained fertility.
- In mammals, sperm guidance in the oviduct appears essential for successful sperm arrival at the oocyte.
- William V.
- Sperm and Egg Transport, Fertilization, and Implantation Among his many accomplishments, Galileo Galilei gave to science, in , two important instruments, the telescope and the microscope.
The human reproductive system is a complex set of intertwining factors, many of which are required for sustained fertility. By interrupting even a single one of these required processes, we can find new ways to create exciting non-hormonal contraceptives for men. One process is sperm transport, or how sperm move through the male reproductive tract.
After sperm are created in the testis , but before they demonstrate motility and fertilize an egg, they must be expelled by the body in a process called ejaculation. Upon ejaculation, sperm are moved from the epididymis to the vas deferens. From there, they move to the urethra, and then out into the wild world.
In a vasectomy , the vas deferens are cut and tied, or sealed to prevent sperm from exiting the body. However, there are multiple groups working on reversible vasectomy, or what we call vas-occlusive devices. These devices work similar to a vasectomy, but instead of cutting the vas deferens, a gel is inserted to block the flow of sperm while allowing fluid movement. Some products such as Echo-VR and Vasalgel propose to do this either through natural degradation of the gel, or by a simple restoration procedure.
Vas-occlusive devices can bring about a new long-term management of fertility for men — one that is reversible. These devices could act for years on end, and would require no maintenance or pill-taking on the part of the user. There are also pharmacological approaches to prevent sperm transport. MCI has funded Sab Ventura of Monash University in Australia to develop his program, which prevents sperm transport by blocking smooth muscle contractions.
Reproduction is a big, complicated machine, with lots of ways to put a temporary hold on the process. Preventing sperm transport is one way that to make the next generation of male contraceptives. Other projects focused on preventing spermatogenesis, sperm motility, and fertilization are all being actively pursued. Basic Clin Androl. Published Apr 5. PMID Lohiya, N. Asian Journal of Andrology. White, C. Development of a P2X1-purinoceptor mediated contractile response in the aged mouse prostate gland through slowing down of ATP breakdown.
Sperm Transport — Mechanisms of Male Contraception. Sperm Motility - Mechanisms of Male Contraception. Spermatogenesis - Mechanisms of Male Contraception. Stopping Sperm Transport — An Old Idea Made New After sperm are created in the testis , but before they demonstrate motility and fertilize an egg, they must be expelled by the body in a process called ejaculation. The vas deferens are sealed to prevent transport of sperm from the epididymis to further stages in the reproductive tract.
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Spermatozoa bound to solid state hyaluronic acid show chromatin structure with high DNA chain integrity: an acridine orange fluorescence study. The thermotactic response The behavioral response of human spermatozoa to a spatial temperature gradient appears to be very similar to their response to a chemoattractant gradient, even though the responses to a temporal gradient are not identical. Specifically, photorelease of the chemoattractant progesterone from its caged compound, evenly distributed in the sperm suspension, resulted in turnings and hyperactivation events, always following a short delay period Figure 1a. The acrosome reaction requires an influx of calcium ions, the efflux of hydrogen ions, an increase in pH, and fusion of the plasma membrane with the outer acrosomal membrane, leading to the exposure and escape of the enzymes contained on the inner acrosomal membrane. Permissions Icon Permissions. The cervix serves as a reservoir, providing a supply of sperm for up to 72 hours. As in bacteria, this random walk is biased by the stimulus — chemotactic, thermotactic, or rheotactic.
Sperm transport mechanisms. Introduction
One key feature of sperm is their ability to swim through the reproductive tract. This ability, or sperm motility, is one of the most exciting targets of male contraception.
Sperm motility is the ability of sperm to swim through the female reproductive tract in order to fertilize an egg. The tail of the sperm, the flagellum, is what gives sperm motility. Powered by ATP, the tail propels sperm towards its target by whipping back and forth.
Sperm motility can be classified in different ways, such as straight-moving, zig zag, vibrating, or just non-motile. These different forms of motility move the sperm in different ways. Exposure to different signals change the guidance mechanism, ultimately guiding the sperm to the egg. Once the sperm nears the egg, they undergo a process called capacitation.
This process is triggered by the presence of calcium, and induces a period of hyperactivation in the sperm. The flagella move with a high curvature and wavelength, propelling the sperm towards the egg.
This step also begins destabilizing the acrosomal membrane, which is crucial for fertilization. Any drug that blocks sperm motility could bring about real change to the contraceptive world.
These drugs could have a very short onset time, and might only need to be taken a short time before coitus. Also, because sperm demonstrate their motility in the female reproductive tract, women might be able to use this contraceptive as well, bringing true equity to the contraceptive landscape.
There are many well-known targets of sperm motility that could be used for development of male contraceptives. Reproduction is a big, complicated machine, with lots of ways to put a temporary hold on the process. Stopping sperm motility is one way that to make the next generation of male contraceptives.
Other projects focused on preventing spermatogenesis, sperm transport, and fertilization are all being actively pursued. Ernesto, J. The Journal of Cell Biology, 7 , — These devices could act for years on end, and would require no maintenance or pill-taking on the part of the user.
There are also pharmacological approaches to prevent sperm transport. MCI has funded Sab Ventura of Monash University in Australia to develop his program, which prevents sperm transport by blocking smooth muscle contractions. Reproduction is a big, complicated machine, with lots of ways to put a temporary hold on the process.
Preventing sperm transport is one way that to make the next generation of male contraceptives. Other projects focused on preventing spermatogenesis, sperm motility, and fertilization are all being actively pursued.
Basic Clin Androl. Published Apr 5. PMID Lohiya, N. Asian Journal of Andrology. White, C. Development of a P2X1-purinoceptor mediated contractile response in the aged mouse prostate gland through slowing down of ATP breakdown.
Sperm Transport — Mechanisms of Male Contraception. Sperm Motility - Mechanisms of Male Contraception. Spermatogenesis - Mechanisms of Male Contraception. Stopping Sperm Transport — An Old Idea Made New After sperm are created in the testis , but before they demonstrate motility and fertilize an egg, they must be expelled by the body in a process called ejaculation.
Mechanisms in Sperm Transport and Fertilization - David Katz
Suarez, A. At coitus, human sperm are deposited into the anterior vagina, where, to avoid vaginal acid and immune responses, they quickly contact cervical mucus and enter the cervix. Cervical mucus filters out sperm with poor morphology and motility and as such only a minority of ejaculated sperm actually enter the cervix. In the uterus, muscular contractions may enhance passage of sperm through the uterine cavity.
A few thousand sperm swim through the uterotubal junctions to reach the Fallopian tubes uterine tubes, oviducts where sperm are stored in a reservoir, or at least maintained in a fertile state, by interacting with endosalpingeal oviductal epithelium. As the time of ovulation approaches, sperm become capacitated and hyperactivated, which enables them to proceed towards the tubal ampulla. Sperm may be guided to the oocyte by a combination of thermotaxis and chemotaxis.
Motility hyperactivation assists sperm in penetrating mucus in the tubes and the cumulus oophorus and zona pellucida of the oocyte, so that they may finally fuse with the oocyte plasma membrane. Knowledge of the biology of sperm transport can inspire improvements in artificial insemination, IVF, the diagnosis of infertility and the development of contraceptives.
Passage of sperm through the female reproductive tract is regulated to maximize the chance of fertilization and ensure that sperm with normal morphology and vigorous motility will be the ones to succeed. Oocytes are usually fertilized within hours of ovulation Austin, ; Harper, On the other hand, in some species, sperm may be inseminated days horses, cattle and pigs or even months some bat species before the arrival of the oocyte.
In humans, there is evidence that fertilization occurs when intercourse takes place up to five days before ovulation Wilcox et al. Because sperm are terminally differentiated cells, deprived of an active transcription and translation apparatus, they must survive in the female without benefit of reparative mechanisms available to many other cells.
Sperm are subjected to physical stresses during ejaculation and contractions of the female tract, and they may sustain oxidative damage. Furthermore, because sperm are allogenic to the female, they may encounter the defenses of the female immune system meant for infectious organisms Menge and Edwards, Thus, sperm must somehow use their limited resources to maintain their fertility in the face of numerous impediments. As it is, of the millions of sperm inseminated at coitus in humans, only a few thousand reach the Fallopian tubes and, ordinarily, only a single sperm fertilizes an oocyte.
The site of semen deposition is not easy to establish in many species because it must be determined by examining the female immediately after coitus and by considering the anatomy of the penis, vagina and cervix during coitus. However, it has been accomplished for humans, in which semen has been observed pooled in the anterior vagina near the cervical os shortly after coitus.
Within minutes of vaginal deposition, human sperm begin to leave the seminal pool and swim into the cervical canal Sobrero and MacLeod, In contrast, rodent sperm deposited in the vagina are swept completely through the cervix into the uterus along with seminal plasma within a few minutes Zamboni, ; Bedford and Yanagimachi, ; Carballada and Esponda, Some species, such as pigs, bypass the vagina altogether and deposit semen directly into the uterine cavity, where sperm may quickly gain access to the oviduct Hunter, ; Roberts, Whereas most of the semen of murine rodents is rapidly transported into the uterine cavity, some remains in the vagina where it coagulates to form a copulatory plug.
The plug forms a cervical cap that promotes sperm transport into the uterus Blandau, ; Matthews and Adler, ; Carballada and Esponda, Ligation of the vesicular and coagulating glands of rats prevented the formation of plugs and the transport of sperm into the uterus Blandau, The plugs formed by semen of guinea pigs and mice extend into the cervical canals and thus could form a seal against retrograde sperm loss Blandau, Male mice deficient for the gene encoding the protease inhibitor known as protease nexin-1 PN-1 show a marked impairment in fertility Murer et al.
Vaginal plugs formed in females after mating with PN-1 null males were small, soft and fibrous and did not lodge tightly in the dual cervical canals. No sperm could be found in the uterus 15 min after mating with PN-1 null males, demonstrating the importance of the plug for promoting transport of mouse sperm into the uterus Murer et al. Human semen coagulates, but it forms a loose gel rather than the compact fibrous plug seen in rodents.
The coagulate forms within about a minute of coitus and then is enzymatically degraded in to 1 h Lilja and Lundwall, The predominant structural proteins of the gel are the 50 kDa semenogelin I and the 63 kDa semenogelin II, as well as a glycosylated form of semenogelin II, all of which are secreted primarily by the seminal vesicles Lilja, The gel is degraded by prostate-specific antigen PSA , a serine protease secreted by the prostate gland Watt et al.
It has been proposed that this coagulum serves to hold the sperm at the cervical os Harper, and that it protects sperm against the harsh environment of the vagina Lundwall et al. Seminal gels are not fully successful at holding sperm at the cervical os. In cattle, several studies have demonstrated loss of sperm from the vagina after mating or insemination reviewed by Hawk, The fate of spermatozoa that are ejaculated or inseminated into the vagina, but that do not enter the cervix, has not been studied extensively in humans.
Like humans, some primates produce semen that forms a soft gel. However, in chimpanzees, a species in which females mate with more than one male in a brief time, the semen coagulates into a compact plug resembling that of rodents Jensen-Seaman and Li , 2 ; Kingan et al.
The plug may serve to prevent other males from mating with the female. Some carnivores e. The vagina is open to the exterior and thus to infection, especially at the time of coitus; therefore, it is well equipped with antimicrobial defenses. These defenses include acidic pH and immunological responses and can damage sperm as well as infectious organisms. To enable fertilization to take place, both the female and the male have adopted mechanisms for protecting sperm. In humans, semen is deposited at the external os of the cervix so that sperm can quickly move out of the vagina Sobrero and MacLeod, Human sperm must contend, however briefly, with the acidic pH of vaginal fluid.
The vaginal pH of women is normally five or lower, which is microbicidal for many sexually transmitted disease pathogens. Evidence indicates that the acidity is maintained through lactic acid production by anaerobic lactobacilli that feed on glycogen present in shed vaginal epithelial cells Boskey et al. Lowering pH with lactic acid has been demonstrated to immobilize bull sperm Acott and Carr, ; Carr et al. The pH of seminal plasma ranges from 6. Vaginal pH was measured by radio-telemetry in a fertile human couple during coitus.
The pH rose from 4. Vaginal washings of women with high levels of detectable seminal antigens had a median pH of 6. Contraceptive gel designed to maintain a low vaginal pH after coitus has been shown to immobilize human sperm in vitro and in vivo Amaral et al. In additions to pH buffers, seminal plasma contains inhibitors of immune responses, including protective components that coat sperm Suarez and Oliphant, ; Dostal et al. These are most effective when sperm are bathing in seminal plasma and may be gradually shed when sperm leave the seminal plasma behind.
Males may also overcome female defenses by inseminating many sperm. This strategy is particularly effective for overcoming cellular immune responses. In the rabbit, deposition of semen results in an invasion of neutrophils into the vagina. This invasion takes time, however, to build to an effective level. Numerous leukocytes, many containing ingested sperm, were recovered from vaginas of rabbits 3—24 h post coitus Phillips and Mahler, a,b.
By that time, however, thousands of sperm had already reached the Fallopian tubes Overstreet et al. In some species, the cervical canal widens under the influence of estrogen. Fluoroscopy and scintigraphy have been used in domestic dogs and cats to examine cervical patency.
Opening of the cervix in these species has been correlated with estrus Silva et al. Radioopaque fluid and also human serum albumin radiolabelled with technetium 99 could be seen rapidly passing through the cervix and filling the uterine lumen after deposition in the cranial vagina at estrus. Sperm of humans and cattle enter the cervical canal rapidly where they encounter cervical mucus Figure 1 A. The extent of hydration is correlated with penetrability to sperm Morales et al. Coitus on the day of maximal mucus hydration in women is more closely correlated with incidence of pregnancy than coitus timed with respect to ovulation detected using basal body temperature Bigelow et al.
Human female reproductive tract illustrating stages of gamete transport. A Sperm entering cervical mucus at external os of cervix. The mucus fills the upper half of the inset. B Sperm interacting with endosalpingeal epithelium in Fallopian tube. C Hyperactivated motility of sperm in Fallopian tube. D Oocyte in cumulus within a transverse section of the tubal ampulla. Artwork by C. Rose Gottlieb. Cervical mucus presents a greater barrier to abnormal sperm that cannot swim properly or that present a poor hydrodynamic profile than it does to morphologically normal, vigorously motile sperm and is thus thought as one means of sperm selection Hanson and Overstreet, ; Barros et al.
The greatest barrier to sperm penetration of cervical mucus is at its border, because here the mucus microarchitecture is more compact Yudin et al. Components of seminal plasma may assist sperm in penetrating the mucus border. Like the vagina, the cervix can mount immune responses. In rabbits and humans, vaginal insemination stimulates the migration of leukocytes, particularly neutrophils and macrophages, into the cervix as well as into the vagina Tyler, ; Pandya and Cohen, Neutrophils migrate readily through midcycle human cervical mucus Parkhurst and Saltzman, In rabbits, neutrophils were found to heavily infiltrate cervices within a h of mating or artificial insemination Tyler, Interestingly, it was discovered that if female rabbits were mated to a second male during the neutrophilic infiltration induced by an earlier mating, sperm from the second male were still able to fertilize Taylor, Thus, although the cervix is capable of mounting a leukocytic response, and neutrophils may migrate into cervical mucus, the leukocytes may not present a significant barrier to sperm.
This can happen in vivo if the female somehow becomes immunized against sperm antigens. Altogether, the evidence indicates that leukocytic invasion serves to protect against microbes that accompany sperm and does not normally present a barrier to normal motile sperm, at least not shortly after coitus.
Immunoglobulins, IgG and IgA, have been detected in human cervical mucus. Secretory IgA is produced locally by plasma cells in subepithelial connective tissue. The amount secreted increases in the follicular phase but then decreases at about the time of ovulation Kutteh et al. The immunoglobulins provide greater protection from microbes at the time when the cervical mucus is highly hydrated and offers the least resistance to penetration.
However, when there are antibodies present that recognize antigens on the surface of ejaculated sperm, infertility can result Menge and Edwards, Complement proteins are also present in cervical mucus Matthur et al. Thus, there is a potential for antibody-mediated destruction of sperm in the cervical mucus as well as leukocytic capture of sperm.
Some anti-sperm antibodies are not complement-activating; however, they can still interfere with movement of sperm through cervical mucus by physical obstruction Menge and Edwards, ; Ulcova-Gallova, An elegant three-dimensional reconstruction of serial sections of the bovine cervix produced by Mullins and Saacke led them to conclude that mucosal folds in the cervical canal form channels leading to the uterine cavity.
Furthermore, based on histochemical staining characteristics of the mucus, they concluded that, during the follicular phase, mucus deep in the channels is different in composition and less dense than that in the central portion of the cervical canal.