Zika Virus Causes Acute Infection and Inflammation in the Ovary of Mice Without Apparent Defects in Fertility.

BACKGROUND: Zika virus (ZIKV) has become a global concern because infection of pregnant mothers was linked to congenital birth defects. Zika virus is unique from other flaviviruses, because it is transmitted vertically and sexually in addition to by mosquito vectors. Prior studies in mice, nonhuman primates, and humans have shown that ZIKV targets the testis in males, resulting in persistent infection and oligospermia. However, its effects on the corresponding female gonads have not been evaluated. METHODS: In this study, we assessed the effects of ZIKV on the ovary in nonpregnant mice. RESULTS: During the acute phase, ZIKV productively infected the ovary causing accumulation of CD4+ and virus-specific CD8+ T cells. T cells protected against ZIKV infection in the ovary, as higher viral burden was measured in CD8-/- and TCRßδ-/- mice. Increased cell death and tissue inflammation in the ovary was observed during the acute phase of infection, but this normalized over time. CONCLUSIONS: In contrast to that observed with males, minimal persistence and no long-term consequences of ZIKV infection on ovarian follicular reserve or fertility were demonstrated in this model. Thus, although ZIKV replicates in cells of the ovary and causes acute oophoritis, there is rapid resolution and no long-term effects on fertility, at least in mice.

Metabolic endotoxaemia--a potential novel link between ovarian inflammation and impaired progesterone production.

INTRODUCTION: Medical conditions such as obesity and inflammatory bowel disease are associated with impaired luteal function, menstrual disturbance and infertility. It is proposed that the disturbance in gut wall integrity ("leaky gut") seen in these conditions may result in the passage of bacterial endotoxin (LPS) from the colonic lumen into the circulation that may initiate inflammation in the ovary and subsequently impair hormone production. METHODS: Quantify the association between systemic levels of LBP, a marker of endotoxin exposure, and levels of inflammation in the ovary (follicular fluid IL-6), plus steroid hormone production in 45 women undergoing IVF treatment. RESULTS: Endotoxaemia (LBP) were positively correlated with plasma CRP and inflammation within the ovary (follicular fluid IL-6). Furthermore, endotoxaemia was negatively correlated with progesterone production. CONCLUSION: The observed correlations, together with previously published animal studies linking endotoxin exposure to impaired luteal function, suggest that the translocation of bacterial endotoxin from the gut lumen into the circulation has the potential to interfere with progesterone production and result in luteal deficiency.

[Efficacy of the psychocorrection methods in the medical rehabilitation of patients with chronic salpingoophoritis and chronic pelvic pain syndrome].

Analysis of efficiency of respiratory relaxational training and of the visualization method was performed for 90 women with chronic salpingoophoritis and the syndrome of chronic pelvic pain. Use of psychocorrection made possible to improve efficiency of the treatment significantly decreasing intensity of the pain and improving psychological status of the patients. Predictors of efficiency and indications for differentiated use of these methods for the medical rehabilitation of patients were worked out.

Pelvic inflammatory disease: diagnosis and treatment in the emergency department [digest].

Pelvic inflammatory disease is a common disease that is associated with significant complications including infertility, chronic pelvic pain, ruptured tubo-ovarian abscess, and ectopic pregnancy. The diagnosis may be delayed when the presentation has nonspecific signs and symptoms. Even when it is properly identified, pelvic inflammatory disease is often treated suboptimally. This review provides evidence-based recommendations for the diagnosis, treatment, disposition, and follow-up of patients with pelvic inflammatory disease. Arranging follow-up of patients within 48 to 72 hours and providing clear patient education are fundamental to ensuring good patient outcomes. Emerging issues, including new pathogens and evolving resistance patterns among pelvic inflammatory disease pathogens are reviewed. [Points & Pearls is a digest of Emergency Medicine Practice].

Selective theca cell dysfunction in autoimmune oophoritis results in multifollicular development, decreased estradiol, and elevated inhibin B levels.

We describe the clinical course of three women with presumptive autoimmune oophoritis who developed multiple follicles but very low to undetectable estradiol levels. Multiple follicles developed spontaneously in all subjects and during pulsatile GnRH treatment for ovulation induction in subject 1. The development of multiple dominant follicles was accompanied by LH levels in the postmenopausal range and FSH levels at the upper limit for premenopausal women. Serum inhibin B levels were elevated appropriately in the setting of multifollicular development, but estradiol levels remained low. Measurement of estradiol precursors demonstrated androstenedione and estrone levels below the 95th percentile in normal women. Adrenal cortical antibodies, and antibodies to 21-hydroxylase and P450 side chain cleavage enzymes were identified in all subjects. All subjects met the criteria for premature ovarian failure during follow-up. Subject 1 later developed adrenal failure, whereas subject 3 had adrenal failure at the time of the study. These subjects elucidate the hormonal pattern in autoimmune oophoritis, before the full criteria for premature ovarian failure are met. The elevated inhibin A and B levels, which accompany the development of multiple small and dominant follicles in these women, suppress FSH relative to LH levels, virtually independent of estradiol. These data provide further evidence for an important role of inhibin B and inhibin A in the negative feedback control of FSH. In addition, the normal inhibin A and inhibin B production in the absence of estradiol precursors and estradiol provide insight into the selective dysfunction of the theca cells in autoimmune oophoritis.

Experimental autoimmune oophoritis. II. Both lymphoid cells and antibodies are successful in adoptive transfer.

Experimental autoimmune oophoritis can be readily induced by passive transfer of peripheral blood lymphocytes, lymph node cells, spleen cells, T- and B-enriched cell suspensions, immune serum and gamma globulins, from ovary antigen immunized rats to naive recipients. Adoptive transfer was markedly enhanced when recipient rats were injected simultaneously with sensitized lymphoid cells and anti-ovary antibodies. Histologically, this passively induced disease was much the same as the actively induced disease. By syngeneic lymph node assay it was shown that regional lymph nodes of neonatally thymectomized rats did not enlarge upon injection of EAOO lymphocytes which otherwise produced a marked effect in lymph nodes of normal recipient rats. Therefore, it appears that enlargement of the draining lymph node was dependent on the participation of host T cells. The possibility that development of EAOO may involve cooperation between antigen-reactive and effector classes of lymphocytes was discussed.

Studies of the pathogenesis of bovine pestivirus-induced ovarian dysfunction in superovulated dairy cattle.

Two experiments (Experiment I, n=12 Holstein-Friesian heifers; Experiment II, n=8 Jersey cows) were conducted to investigate the pathogenesis of bovine pestivirus-induced ovarian dysfunction in cattle. In both experiments the cattle were superovulated with twice daily injections of a porcine pituitary extract preparation of follicle stimulating hormone (FSH-P), for 4 days commencing on Day 10+/-2 after a presynchronised oestrus. The heifers received a total dose of 30 mg and the cows 32 mg of FSH-P. Prostaglandin F(2alpha) (PGF(2alpha)) was administered 48 h after commencement of superovulation and all cattle were artificially inseminated (AI) between 48 and 66h after PGF(2alpha) treatment. In both experiments bovine pestivirus seronegative cattle (Experiment I, n=6; Experiment II, n=4) were inoculated intranasally with an Australian strain of non-cytopathogenic bovine pestivirus (bovine viral diarrhoea virus Type 1) 9 days prior to AI. Bovine pestivirus infection was confirmed by seroconversion and/or virus isolation in all of the inoculated cattle, consistent with a viremia occurring approximately between Day 5 prior to AI and the day of AI. Ovarian function was monitored in both experiments by daily transrectal ultrasonography and strategic blood sampling to determine progesterone, oestradiol-17beta, luteinising hormone (LH) and cortisol profiles. Non-surgical ova/embryo recovery was performed on Day 7 after AI. In Experiment II half the cattle were slaughtered on Day 2 and the remainder on Day 8 after AI, and the ovaries submitted for gross and histopathological examination including immunohistochemistry to demonstrate the presence of bovine pestivirus antigen. In both studies, comparisons were made between infected and confirmed uninfected (control) animals. Overall the bovine pestivirus infected cattle had significantly lower (P<0.05) ova/embryo recovery rates compared to the control cattle. There was evidence of either an absence (partial or complete) of a preovulatory LH surge or delay in timing of the LH peak in the majority (90%) of infected heifers and cows, and histologically, there was evidence of non-suppurative oophoritis with necrosis of granulosa cells and the oocyte in follicles from the infected cows. By contrast only 20% of the control heifers and cows had evidence of absence of a pre-ovulatory LH surge. These experiments collectively demonstrate that bovine pestivirus infection during the period of final growth of preovulatory follicles may result in varying degrees of necrosis of the granulosa cells with subsequent negative effects on oestradiol-17beta secretion which in turn negatively affects the magnitude and/or timing of the preovulatory LH surge.

[The function of the hepatobiliary system in patients who have had inflammatory diseases of the uterus and adnexa]. / Funktsionalno sustoianie na khepato-biliarnata sistema pri bolni, prekarali vuzpalitelni zaboliavaniia na matkata i adneksite.

The function of the hepatobiliary system was studied on 60 women, undergone inflammatory diseases in the uterus and adnexa. The women of the basic group (n = 60) were divided into two subgroups in accordance with the state of genital organs. The first subgroup (n = 39) included women with residual manifestation of chronic salpingo-oophoritis. The second subgroup (n = 21) included women with tumours and tumour-like processes of genital organs, occurred on the back ground of a continuous inflammatory process. The control group included 10 healthy women. Dynamic scintigraphy of the liver and gallbladder utilizing Tc99 radionuclide with short duration of life, was used to determine the functional state of the liver and gallbladder together with biochemical parameters of blood. The obtained results showed that there were significant changes in hepatobiliary system of women with residual manifestations of chronic salpingo-oophoritis. In women with tumours and tumour-like processes of genitals, occurred on the background of continuous inflammatory process, there were significant disturbances in the engulfing-depurating function of the liver and gallbladder of hypokinetic type.

[The comparative efficacy of different methods of cryotherapy in patients with chronic salpingo-oophoritis]. / Sravnitel'naia éffektivnost' razlichnykh metodik krioterapii u bol'nykh khronicheskim sal'pingooforitom.

Therapeutic response to treatment (vaginal and external cryotherapy, drugs) in 97 patients with chronic salpingo-oophoritis at reproductive age provides the conclusion on effectiveness of various cryotherapeutic regimens in this disease. Cryotherapy improves regional blood circulation, restores contractility of the uterine tubes.

[The comparative effect of classic massage of different intensities on patients with chronic salpingo-oophoritis]. / Sravnitel'noe vliianie klassicheskogo massazha razlichnoi intensivnosti na bol'nykh khronicheskim sal'pingooforitom.

Massotherapy in different regimens has been used in 30 patients in remission of chronic salpingo-oophoritis (CSO). The massage produced positive changes in blood coagulation, immune status, regional hemodynamics of the small pelvis, bioelectric activity of the muscles of the anterior abdominal wall and lumbosacral region. A strong anesthetic and antiinflammatory effect of intensive massage in 78%, recovered reproductive function in 33% of the patients allow to recommend intensive massage as possible monotherapy of patients in remission of CSO.

[A comparative assessment of different cryotherapy methods for patients with chronic nonspecific salpingo=oophoritis]. / Sravnitel'naia otsenka razlichnykh metodik krioterapii bol'nykh khronicheskim nespetsificheskim sal'pingooforitom.

97 females at reproductive age with chronic nonspecific salpingo-oophoritis (CNSO) were examined and treated. The results of the treatment (vaginal and external impact) demonstrate positive effects of various cryotherapeutic techniques on CNSO clinical course, on hormonal and immune unbalance, functional activity of the uterine tubes, regional hemodynamics, psychoemotional status. Thus, cryotherapy is an effective adjuvant in combined therapy of CNSO.

[The interference-current therapy of chronic salpingo-oophoritis (a trial of studying the regional hemodynamics)]. / Interferentsionnaia terapiia khronicheskogo sal'pingooforita (opyt izucheniia regionarnoi gemodinamiki).

Blood redistribution in blood circulatory beds (the uterus, external genitalia and vagina) and as a whole have been established in exposure to interference currents. Ka index of rheoencephalography may be used as an additional objective criterion of individual sufficiency of physiotherapeutic exposure.

[The combined treatment of patients with chronic nonspecific salpingo-oophoritis using a low-frequency magnetic field and iodobromine water]. / Kompleksnoe lechenie bol'nykh khronicheskimi nespetsificheskimi sal'pingooforitami nizkochastotnym magnitnym polem i iodobromnoi vodoi.

The studies of 116 females with chronic nonspecific salpingo-oophoritis demonstrate that combination of low-frequency magnetic field with iodine-bromine water effectively corrects immunological indices, i.e. improves T- and B-cell immunity, production of IgM and IgA, proportion of immunoregulatory subpopulations of T-lymphocytes.