Probiotic intervention as a potential therapeutic for managing gestational disorders and improving pregnancy outcomes.

Recent molecular investigations have significantly developed our knowledge of the characteristics of the reproductive microbiome and their associations with host responses to provide an ideal milieu for the development of the embryo during the peri-implantation period and throughout pregnancy as well as to provide a successful in vitro fertilization and appropriate reproductive outcomes. In this context, the establishment of microbial homeostasis in the female reproductive tract, in various physiological periods, is a substantial challenge, which appears the application of probiotics can facilitate the achievement of this goal. So that, currently, probiotics due to its safe and natural features can be considered as a novel biotherapeutic approach. In this review, we comprehensively discuss the bacterial, fungal, and viral diversity detected in the reproductive tract, and their associations with the establishment of dysbiosis/eubiosis conditions as well as we present the significant outcomes on probiotic intervention as an efficient biotherapeutic strategy for management of gestational disorders and improve pregnancy outcomes.

Vitamin D Status Impacts Genital Mucosal Immunity and Markers of HIV-1 Susceptibility in Women.

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

Interferon epsilon in the reproductive tract of healthy and genital herpes simplex virus-infected pregnant women: Results of a pilot study.

PROBLEM: Recently characterized interferon epsilon (IFNe) protects against sexually transmitted infections, including genital herpes simplex virus (HSV), in animal models. There are no reports of IFNe in genital tract secretions of pregnant women, and data on IFNe in non-pregnant women are limited. This pilot study is the first to measure concentrations of IFNe in vaginal and cervical secretions during pregnancy and compare values between healthy and genital HSV-infected women. METHOD OF STUDY: Vaginal or cervical specimens from 30 pregnant women were obtained from the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) repository. Cervical samples were collected during the first trimester and vaginal samples across pregnancy. Enzyme-linked immunosorbent assay determined concentrations of IFNe (pg/mL). Data for IFNe were log-transformed and compared by maternal demographics, clinical variables, and HSV status using t tests and linear regression. Repeated measures analysis explored trends across pregnancy. RESULTS: Among the entire cohort, first trimester concentrations of IFNe in vaginal or cervical secretions decreased as body mass index increased (ß = -0.14, P = .0466). Concentrations of vaginal IFNe increased across pregnancy in HSV-infected and healthy women (P = .009). Average vaginal IFNe across pregnancy was lower in women with HSV compared to healthy women (P = .0009). CONCLUSION: Interferon epsilon increased across pregnancy, but was less abundant in women with HSV. This pilot investigation cannot make any definitive conclusions. However, animal models suggest that IFNe may protect against STIs. Thus, larger studies are required to validate expression of IFNe in the reproductive tract of pregnant women with and without genital infections.

Molecular regulators of resolution of inflammation: potential therapeutic targets in the reproductive system.

Inflammatory processes are central to reproductive events including ovulation, menstruation, implantation and labour, while inflammatory dysregulation is a feature of numerous reproductive pathologies. In recent years, there has been much research into the endogenous mechanisms by which inflammatory reactions are terminated and tissue homoeostasis is restored, a process termed resolution. The identification and characterisation of naturally occurring pro-resolution mediators including lipoxins and annexin A1 has prompted a shift in the field of anti-inflammation whereby resolution is now observed as an active process, triggered as part of a normal inflammatory response. This review will address the process of resolution, discuss available evidence for expression of pro-resolution factors in the reproductive tract and explore possible roles for resolution in physiological reproductive processes and associated pathologies.

[Analysis of parameters of reproductive tract mucosal immunity in women with chlamydial infection before and after local magnetolaserotherapy].

The objective of the present study was to evaluate the influence of combined treatment with low-intensity laser radiation and magnetic field on neutrophil function in women presenting with Chlamydial infection. Dysfunction of neutrophil granulocytes in these patients was manifest in the first place as the decreased number of phagocytes and the low rate of phagocytosis. It was shown that the concentration of active oxygen species in neutrophils in the patients with Chlamydial infection was significantly smaller than in healthy women. The concurrent application of low-intensity laser radiation and a magnetic field not only stimulated phagocytosis but also increased intracellular production of active oxygen species especially under in vitro conditions. It is concluded that combined treatment with low-intensity laser radiation and magnetic field has beneficial effect on the parameters of mucosal immunity in the reproductive tract of women with Chlamydial infection.

Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice.

BACKGROUND: Worldwide, vaginal transmission now accounts for more than half of newly acquired HIV-1 infections. Despite the urgency to develop and implement novel approaches capable of preventing HIV transmission, this process has been hindered by the lack of adequate small animal models for preclinical efficacy and safety testing. Given the importance of this route of transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1 infection. METHODS AND FINDINGS: We show that the female reproductive tract of humanized bone marrow-liver-thymus (BLT) mice is reconstituted with human CD4+ T and other relevant human cells, rendering these humanized mice susceptible to intravaginal infection by HIV-1. Effects of HIV-1 infection include CD4+ T cell depletion in gut-associated lymphoid tissue (GALT) that closely mimics what is observed in HIV-1-infected humans. We also show that pre-exposure prophylaxis with antiretroviral drugs is a highly effective method for preventing vaginal HIV-1 transmission. Whereas 88% (7/8) of BLT mice inoculated vaginally with HIV-1 became infected, none of the animals (0/5) given pre-exposure prophylaxis of emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) showed evidence of infection (Chi square = 7.5, df = 1, p = 0.006). CONCLUSIONS: The fact that humanized BLT mice are susceptible to intravaginal infection makes this system an excellent candidate for preclinical evaluation of both microbicides and pre-exposure prophylactic regimens. The utility of humanized mice to study intravaginal HIV-1 transmission is particularly highlighted by the demonstration that pre-exposure prophylaxis can prevent intravaginal HIV-1 transmission in the BLT mouse model.

Anti-acrosin antibodies in sera, colostrum and genital organs of vaccinated ewes: estimation and correlation with fertility.

Three ewes were vaccinated with boar sperm acrosin. Despite the presence of antiacrosin antibodies which crossreact with ram acrosin in the sera of the immunized sheep, no significant reduction in fertility was observed. Incubation of ejaculated or capacitated boar spermatozoa with anti-acrosin serum or IgG did not reduce the halos of digestion in the gelatinolysis test. However, an unexplained decrease of the forward progression and number of lytically active spermatozoa was observed after this treatment. We found antiacrosin antibodies and determined their titers in the sera of the vaccinated ewes, in colostrum and in aqueous extracts of cervix, uterus, oviduct and ovary. No antiacrosin antibodies could be detected in the sera of new born lambs. The immunoglobulins IgA, IgG and IgM were isolated from the sera of the ewes. The acrosin-specific antibodies belonged exclusively to the IgG class. In genital extracts the amount of IgG, IgA and IgM was determined. IgG was found in higher amount in every extract. IgA is present in similar amount only in the cervix, in the other parts only in traces. In all extracts IgM is found in a very low level. The specificity of the antibodies for acrosin was proven by active enzyme staining of the precipitin lines obtained by immunodiffusion.