Female Reproductive Tract Secretions Research Articles

Infertility: a pathologic condition or selection against genetic incompatibility?

Infertility is currently regarded as a male or female-dependent pathologic condition. However, emerging evidence suggests that this may be an incomplete view as it misses the important fact that the gametes of some males and females often have higher compatibility than others. In this article, I present recent evidence demonstrating that female reproductive tract secretions in humans mediate “mate choice” at the level of the gametes, and this way likely bias fertilization toward immunologically or otherwise compatible males. A better understanding of this evolutionary selection process may open up novel possibilities for the future development of more personalized infertility diagnostics and treatments.

Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.

Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM) by vaginal inoculation with 104–106 plaque-forming units (PFU). However, there was variability in susceptibility between the individual RM with 1–>8 vaginal inoculations required to establish infection. After treatment with Depoprovera, a widely used contraceptive progestin, two RM that initially resisted 8 vaginal ZIKV inoculations became infected after one ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal ZIKV transmission. Unexpectedly, the kinetics of virus replication and dissemination after intravaginal ZIKV inoculation were markedly different from RM infected with ZIKV by subcutaneous (SQ) virus inoculation. Several groups have reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma with vRNA less common in urine and saliva and only rarely detected in female reproductive tract (FRT) secretions. In contrast, in vaginally inoculated RM, plasma vRNA is delayed for several days and ZIKV replication in, and vRNA shedding from, the FRT was found in all 6 animals. Further, after intravaginal transmission ZIKV RNA shedding from FRT secretions was detected before or simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV replication in the FRT was independent of, and often preceded virus replication in the tissues contributing to plasma vRNA. These results support the conclusion that ZIKV preferentially replicates in the FRT after vaginal transmission, but not after SQ transmission, and raise the possibility that there is enhanced fetal infection and pathology after vaginal ZIKV transmission compared to a mosquito transmitted ZIKV.

Differential susceptibility of HIV strains to innate immune factors in human cervical-vaginal secretions

Differential susceptibility of HIV strains to innate immune factors in human cervical-vaginal secretions Mimi Ghosh, John V Fahey, Charles R WiraDepartment of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, New Hampshire, USAAbstract: The female reproductive tract (FRT) is protected by innate and adaptive immune mechanisms, which work in concert to defend against human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). Under the control of sex hormones throughout a woman’s life, the immune system in the FRT has evolved to meet the challenges of protection against STIs, coupled with the need to sustain the development of new life. The studies presented in this review focus on the threat of HIV infection and the levels of protection present in the FRT during the menstrual cycle. Studies from our laboratory and others, examined the presence and variability of immune components against viral infection in the FRT. Our findings indicate that there are some factors in the FRT secretions that inhibit and enhance infectivity of individual strains of HIV. Given the complexities of hormonal regulation, identification of the elements involved in susceptibility to and protection against HIV in women must involve a careful analysis of transmitted viruses and a clear understanding of immune protection in the FRT.Keywords: HIV susceptibility, CVL

Receptors in Spermatozoa: Are They Real?

Receptors in Spermatozoa: Are They Real?

The sequential effects of human cervical mucus, oviductal fluid, and follicular fluid on sperm function

To compare the sequential effects of human cervical mucus (CM), oviductal fluid, and follicular fluid (FF) on sperm motility, hyperactivation, and the acrosome reaction during 9 hours of incubation in vitro. Spermatozoa from a fertile donor were allowed to penetrate human CM in vitro and then were recovered and incubated in either 30% human oviductal fluid or a simple salt solution for 3 hours before challenge with 20% FF. Thus, the sequential effects of the fluids collected from the female reproductive tract on sperm hyperactivation and acrosome reaction were examined. The donor insemination program at the University Clinic within the Jessop Hospital for Women, Sheffield, United Kingdom. All donors used in this study were involved in the donor insemination program. Sperm motility, hyperactivation, and percentage of acrosome-reacted spermatozoa were measured. This study used an in vitro technique to mimic sperm transport in vivo. Spermatozoa sequentially incubated with female reproductive tract secretions in vitro showed a maintenance in the level of FF-induced hyperactivated motility and a decreased response to the FF-induced acrosome reaction when compared with sperm challenged with FF in the absence of prior incubation with human oviductal fluid. It is suggested that human oviductal fluid may serve to delay the FF-induced acrosome reaction.

Sexual transmission of human immunodeficiency virus: virus entry into the male and female genital tract

This review of the risks of heterosexual transmission of HIV examines what is known about routes of viral entry into the ejaculate and into female reproductive tract secretions routes of viral passage from the ejaculate into the female and from female reproductive tract secretions. The risk of transmission of HIV during heterosexual exposure is much lower than that of gonorrhea or hepatitis B (about 25%) estimated at about 0.3% per event. Probably certain factors such as a male IVDU partner greatly increase this risk. Most of the HIV in semen resides in the CD4-positive lymphocytes and macrophages of which there are about 1 million per ejaculate. Greater risk of transmission occurs in men with STDs because there are more white blood cells disrupted genital epithelium with activated white cells at the site immunosuppression in some STDs and facilitated HIV disease process with some STDs notably cytomegalovirus. The site of uptake of HIV into the female reproductive tract is not known whether the vagina cervix or uterus. Exposure to semen causes local immunosuppression especially in the rectum. Whether use of oral contraceptives IUDs diaphragms or sponges affects HIV binding to the female tract remains to be studied. No data exist on the effects of vaginal spermicides either the commonly used nonoxynol-9 or other substances known to be potent virucides on HIV survival in vivo. One study in rhesus monkeys showed that the 100% killing of HIV seen in vitro is reduced to 50% in vivo. Mucosal cells are known to stimulate budding of mature HIV virions from CD4- lymphocytes during mutual contact. The tissue source of HIV in the sexual secretions of HIV-positive women whether blood cervical or vaginal secretions is unknown. How HIV enters the male tract during exposure is unknown although lack of circumcision is a risk factor. Possible animal models for research on these issues are discussed. Research is needed to determine the site of entry of HIV into reproductive tissues risks throughout the menstrual cycle and protective effects of contraceptives as result of this knowledge.

Adenylate cyclase activity in porcine sperm in response to female reproductive tract secretions

AbstractAdenylate cyclase activities were studied in porcine sperm in the presence and absence of Mn++ before and after incubation in vivo and in vitro. Incubation of sperm in vivo for 30 min increased the Mg++‐stimulated adenylate cyclase activity from 35.1 pmoles cyclic AMP formed per mg protein per 10 min to 50.4 pmoles. The activity stimulated by Mg++ and Mn++ increased from 392 to 729 pmoles after 30 min of in vivo incubation. Activity after incubation in vivo for 120 min was not different from activity after 30 min. In vitro incubation of porcine sperm in Ca++‐free Ringer‐fructose resulted in no change, but incubation in oviductal and uterine flushings obtained from gilts soon after ovulation increased Mg++‐stimulated activity by 24% and Mg++−+ Mn++‐stimulated activity by 49%. In vitro incubations in preovulatory flushings plus follicular fluid or in bovine serum albumin also increased adenylate cyclase activity.

Effects of female reproductive tract secretions on rabbit sperm. 3. Acrosomal enzyme changes related to capacitation.

SummaryRabbit sperm incubated in uterine fluid in vitro did not show any decrease in acrosomal proteolytic activity. There is a measureable decrease in acrosomal hyaluronidase activity following incubation in postovulatory uterine fluid, but not during incubation in pre-ovulatory uterine fluid. Rabbit sperm incubated in post-ovulatory uterine fluid for 5 hr were capable of fertilizing ova and were considered to be capacitated. Sperm incubated past the time of hyaluronidase release were not capable of fertilizing ova. It is believed that the release of hyaluronidase by rabbit sperm incubated in uterine fluid is related to the completion of the process of capacitation. Thus, the release of hyaluronidase can be used, under the proper conditions, as an end point for the study of in vitro capacitation of rabbit sperm.

Effects of female reproductive tract secretions on rabbit sperm. I. Release of hyaluronidase in vitro.

SummaryThe release of hyaluronidase by rabbit sperm was measured during in vitro incubation, in: (a) distilled water, (b) Tyrode's solution, and (c) rabbit uterine fluid. There was no apparent release of hyaluroni-dase in fluid obtained from the uterus of an estrus rabbit and collected prior to HCG-induced ovulation. In fluid obtained after HCG-induced ovulation, increases in hyaluronidase activity occurred, indicating hyaluronidase release by the sperm. The peak of maximum hyaluronidase activity was related to the timing of the fluid collection. In contrast, no discernible peak of hyaluroni-dase activity occurred when sperm were incubated in Tyrode's solution or in distilled water. Postovulatory uterine fluid appears to actively promote the release of hyaluronidase from sperm.

Effects of female reproductive tract secretions on rabbit sperm. II. Control of sperm hyaluronidase release.

SummaryThe release of hyaluronidase by rabbit sperm was measured, in vitro: (a) in uterine fluid from unilaterally ovariectomized rabbits, (b) in uterine fluid heated to 56°, (c) in postovulatory uterine fluid with added progesterone, and (d) in protein containing fractions of uterine fluid. Ovariectomy suppresses sperm hyaluronidase release as does heating of the uterine fluid or the increased availability of progesterone. The hyaluronidase releasing activity of uterine fluid is confined to one macromolecular fraction following gel filtration. The possible relationship of these results to the process of capacitation is discussed.

The carbohydrate content of sow uterine flushings.

It has been observed that the major free sugar component occurring in female reproductive tract secretions is glucose and the occurrence of fructose has not been reported except in trace quantities (Bishop, 1956; Lutwak-Mann, 1962). Unpublished observations in this laboratory have confirmed that glucose is the major free sugar in uterine flushings from the rat, rabbit, cow and sheep, and other sugars, when present, occur in much smaller amounts. In uterine flushings of the sow, however, a different situation exists. These observations are based on uterine flushings taken from gilts penned together and examined for oestrous behaviour daily, using a boar which was not allowed to mate. The animals were not used until they had shown visible signs of two oestrous periods. They were divided randomly into four groups and uterine flushings collected at times subsequent to first standing for the boar as follows : Group 1, 6 hr (no animal in this group had ovulated) ; Group 2, 48 hr (all animals had recently ovulated); Group 3, 4 days; and Group 4, 10 days. An additional group (Group 5) was added during the experiment and con¬ sisted of pigs which were examined at the second or third observed heats, but which had never ovulated and had infertile uteri. The uterus was exposed by laparotomy under Nembutal and Fluothane anaesthesia and each uterine horn was flushed from the utero-tubal junction to the cervix with 100 ml of a sterile saturated solution of lithium carbonate (Heap, 1962). Recoveries, based on volume of lithium carbonate varied from 65 to 100%. The flushing from each horn was analysed separately. Appropriate aliquots of the flushings were subjected to chromatography on Amberlite IR-120(H) and IR-45(OH) ion exchange resins by the method of Romberger & Norton (1961) and total sugar determinations (Trevelyan & Harrison, 1952) were carried out on the neutral eluate. Concentrations of the eluates