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.

Enterobius vermicularis in tubo-ovarian abscess: A rare and interesting incidental finding - A case Report.

Enterobius vermicularis is a common intestinal nematode; however, rare extraintestinal Enterobius infections have been reported from different parts of the world. Here, we present a case of tubo-ovarian abscess in an otherwise healthy young sexually active female with no known comorbids with history of on and off lower abdominal pain for one year and high grade fever for one month. On the basis of further workup and radiological evaluation, a preoperative diagnosis of right sided tubo-ovarian abscess was made and salpingo-oophorectomy was performed laproscopically in July 2015. Histopathology of the resected tissue revealed necrosis and in one area Enterobius vermicularis was identified surrounded by neutrophils and eosinophil rich abscess. A final diagnosis of severe acute and chronic salpingo-oophoritis with abscess formation, secondary to Enterobius vermicularis was made. Signs and symptoms of parasitic involvement in tubo-ovarian abscesses are not much different than usual presentations of pelvic inflammatory diseases and identification of a parasite in a tubo-ovarian tissue sample is a rare clinical finding. A high index of suspicion on the part of histopathologist as well as clinician is important for timely diagnosis and effective management of such cases.

Bidirectional Estrogen-Like Effects of Genistein on Murine Experimental Autoimmune Ovarian Disease.

This study was to investigate the bidirectional estrogen-like effects of genistein on murine experimental autoimmune ovarian disease (AOD). Female BALB/c mice were induced by immunization with a peptide from murine zona pellucida. The changes of estrous cycle, ovarian histomorphology were measured, and the levels of serum sex hormone were analyzed using radioimmunoassay. Proliferative responses of the ovary were also determined by immunohistochemistry. Administration of 25 or 45 mg/kg body weight genistein enhanced ovary development with changes in serum sex hormone levels and proliferative responses. Meanwhile, the proportions of growing and mature follicles increased and the incidence of autoimmune oophoritis decreased, which exhibited normal ovarian morphology in administration of 25 or 45 mg/kg body weight genistein, while a lower dose (5 mg/kg body weight genistein) produced the opposite effect. These findings suggest that genistein exerts bidirectional estrogen-like effects on murine experimental AOD, while a high dose (45 mg/kg body weight) of genistein may suppress AOD.

Controlled reperfusion for different durations in the treatment of ischemia-reperfusion injury of the rat ovary: evaluation of biochemical features, molecular gene expression, and histopathology.

High numbers of proinflammatory cells (PMNLs), which are carried by the blood to ischemic tissue during reperfusion, are considered responsible for inducing the inflammatory response that occurs in ischemia-reperfusion (I/R) injury. Our objective was to determine the controlled reperfusion (CR) interval duration (CRID) that would minimize the injury caused by the PMNLs that infiltrate ischemic tissue. Animal groups were divided into the following groups: Sham group, ovarian I/R group (OIR), and ovarian ischemia controlled-reperfusion groups OICR-1, OICR-2, OICR-3, OICR-4, OICR-5, OICR-6, which had their ovarian artery opened and then closed for 10, 8, 6, 4, 2, or 1 s, respectively. The results show that the COX-2 activity and the gene expression decreased while the COX-1 activity and the gene expression were found to be increased in parallel to the shortening of the period in CRID. From the histopathological examinations, the findings of hemorrhage, edema, congested vascular structures, degenerated cells, and migration and adhesion of PMNLs were scaled as follows: Sham group < OICR-6 < OICR-5 < OICR-4 < OICR-3 < OICR-2 < OICR-1. The results from the histopathological assessments were consistent with the molecular and biochemical findings. In conclusion, our findings suggest that increased COX-2 activity plays a role in I/R injury of the rat ovary, and that controlled reperfusion for 3, 2, or 1 s following 2 h of ischemia may attenuate the effects of I/R injury.

Xanthogranulomatous endometritis with unilateral salpingo-oophoritis in a postmenopausal woman masquerading as a malignancy.

Xanthogranulomatous endometritis (XGE) is a rare pathological entity which is characterised by sheets of foamy histiocytes and lymphoplasmacytic infiltrates. This condition can mimic endometrial carcinoma. We report a case, clinically suspected as carcinoma of the endometrium/ovary, which was diagnosed as XGE with left salpingo-oophoritis on histopathology.

Nigella sativa reduces tissue damage in rat ovaries subjected to torsion and detorsion: oxidative stress, proinflammatory response and histopathological evaluation.

BACKGROUND: To evaluate biochemically and histopathologically the effects of Nigella sativa (NS) in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries. METHODS: Thirty-six female rats were divided into 6 groups: group I = sham operation; group II = 500 mg/kg NS + sham operation; group III = bilateral ovarian ischemia; group IV = 500 mg/kg NS + ischemia; group V = 3-hour period of ischemia + 3-hour reperfusion, and group VI: 3-hour period of ischemia + 500 mg/kg NS 2.5 h after the induction of ischemia + 3-hour reperfusion. At the end of ischemia, the bilateral vascular clips were removed, and 3-hour reperfusion was continued. IL-1ß, IL-6, and TNF-α cytokine levels in serum, and superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH), and malondialdehyde (MDA) levels were determined. RESULTS: I/R increased the MDA level and MPO activity while significantly decreasing the SOD activity and GSH level when compared to the sham. The 500-mg/kg dose of NS before I/R reversed the trend in MDA levels, MPO activity, SOD activity, and GSH levels. Ischemia and I/R increased the serum levels of IL-1ß, IL-6, and TNF-α, while the administration of NS decreased the serum levels of these cytokines. CONCLUSIONS: The administration of NS is effective in reversing tissue damage induced by ischemia and/or I/R in ovaries.

Xanthogranulomatous salpingo-oophoritis presenting as an ovarian tumour.

Xanthogranulomatous salpingo-oophoritis (XGSO) is an exceptionally rare entity. Its clinical manifestations and imaging modalities can mimic benign and malignant adnexal diseases, making it difficult to diagnose. Here we report a case of XGSO in a young woman who was operated with suspicion of a borderline ovarian tumour. Preoperative diagnosis of XGSO should be considered to avoid radical surgical treatment, especially in young patients.

An unusual case of adult filarial oophoritis.

Ovaries are the least involved site of infection in the female genital tract. Parasitic infestations of the ovary are even rarer. We report an unusual case of adult filariasis of the ovary discovered incidentally on histopathologic examination. Panhysterectomy was performed on a 47-year-old north Indian woman with multiple uterine fibroids, where menorrhagia was unresponsive to hormonal therapy. An adult nongravid female filarial worm was identified in the dilated ovarian lymphatic system. The host local immune response was minimal. Subsequent work-up failed to show any physical stigmata or diagnostic evidence of the disease. The structural details of the adult worm are characteristic to permit its recognition on histologic examination. The involvement of an adult worm in the female genital tract is distinctly uncommon in comparison with the male genital involvement. Till date, only a handful of cases of ovarian adult filariasis are reported.

Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease.

Organ-specific autoimmune diseases such as oophoritis, gastritis, thyroiditis, and orchitis were induced in female or male nude (nu/nu) mice by the transfer of nu/+spleen cells from which particular Lyt T cell subset(s) had been removed: nu/+spleen cells treated with anti-Lyt-1 plus complement (C) caused disease in recipient nude mice; anti-Lyt-2 plus C-treated spleen cells, in contrast, did not. The cells responsible for disease induction are believed to be Thy-1+, Lyt-1-, 2,3- (Thy-1, Lyt-1, 2,3), since spleen cells treated with mixed antisera, including anti-Lyt-1 and anti-Lyt-2, plus C, could induce the disease with almost the same incidence as anti-Lyt-1 plus C-treated cells (oophoritis 50%, gastritis 25%, thyroiditis 10-20%, and orchitis 40%). Cells treated with mixed antisera of anti-Thy-1, anti-Lyt-1, and anti-Lyt-2, plus C, could not induce autoimmune disease. Each induced autoimmune disease could be adoptively transferred to other nude mice via spleen cells, with resulting histological lesion of corresponding organs and development of specific circulating autoantibodies. Since anti-Thy-1 plus C treatment of donor spleen cells abrogated the capacity to transfer the disease, we conclude that T cells are required as effector cells, and that these may develop from Lyt-1-, 2,3- cells. Lyt-1+, 2,3- cells were demonstrated to have suppressive activity upon the development of the diseases; induction of autoimmunity was completely inhibited by the cotransfer of Lyt-1+, 2,3- cells with Lyt-1-, 2,3- cells. When anti-Lyt-2 plus C-treated cells (i.e., Lyt-1+, 2,3- and Lyt-1-, 2,3- cells) were mixed with anti-Lyt-1 and anti-Lyt-2 plus C-treated cells (i.e., Lyt-1-, 2,3- cells) in various ratios, then transferred to nude mice, the development of each autoimmune disease was clearly inhibited, even by small doses of Lyt-1+, 2,3- cells. The autoimmune disease we were able to induce was quite similar to human organ-specific autoimmune disease in terms of the spectrum of organs involved, histopathological features, and the development of autoantibodies to corresponding organ components (oocytes, parietal cells, thyroid colloid, including thyroglobulin, and sperm).(ABSTRACT TRUNCATED AT 400 WORDS)

Study on cellular events in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt-1 effector cells for oocytes damage after adoptive transfer.

Neonatal thymectomy during the critical period, 2-4 d after birth, can induce various organ-specific autoimmune diseases including oophoritis in A/J mice. The oophoritis thus induced was passively transferred into neonatal mice by injection of spleen cells obtained from syngeneic donors with the disease. Recipient ovaries were rapidly damaged with remarkable mononuclear cell infiltration and destruction of follicular structures. The phenotype of effector cells responsible for successful adoptive transfer was found to be Thy-1+, Lyt-1+,23-, Ia-, Qa-1-, and was sensitive to antithymocyte serum treatment but resistant to cyclophosphamide treatment or in vitro X-ray irradiation. The compatibility between donor and recipient at the major histocompatibility complex was not required for the effector phase of transfer. The oophoritis induced in BALB/c (nu/+ or +/+) was also shown to be transferred into athymic BALB/c nude mice with resulting ovarian lesion and circulating autoantibodies against oocytes. In this transfer system, the effector cells were also demonstrated to be T cells with the Lyt-1+,23- phenotype. Adoptive transfer experiments in both systems revealed that the destruction of ovaries in postthymectomy autoimmune oophoritis was mediated by Lyt-1 T cells. Whether these T cells can be distinguished from other Lyt-1 cells, such as T helper cells and effector T cells in delayed-type hypersensitivity (DTH), is not clear at present, but the results suggest that the effector mechanisms may be closely related to a DTH reaction.

Tubo-ovarian abscess infected by Salmonella typhi.

We report a case of a tubo-ovarian abscess infected with Salmonella enterica serotype typhi A 19-year-old Nepalese woman presented to a hospital in Kathmandu with lower abdominal pain, constipation, fever and a non-healing, suppurative surgical wound from an emergency caesarian section performed 2 months previously at 37 weeks of pregnancy. She also had an exploratory laparotomy for an appendix perforation with peritonitis at 25 weeks of gestation. Her wound infection did not respond to cloxacillin and she had an exploratory laparotomy, and a tubo-ovarian abscess was found from which S. typhi was isolated. She had a bilateral salpingo-oophorectomy and responded to 14 days of chloramphenicol. A tubo-ovarian abscess is a rare complication of enteric fever.

Xanthogranulomatous oophoritis mimicking malignancy: a diagnostic dilemma.

Xanthogranulomatous inflammation is a chronic condition in which the affected organ is replaced by lipid-filled macrophages with plasma cells, lymphocytes and neutrophils. It is very rare in the ovaries. A case of xanthogranulomatous oophoritis in a premenopausal multiparous woman presenting with abnormal uterine bleeding and adnexal mass whose clinical and imaging findings suggested malignancy is reported.

Autoimmune oophoritis: a rarely encountered ovarian lesion.

Autoimmune oophoritis is a rare disorder causing ovarian failure clinically characterized by amenorrhea and infertility. It often occurs in a setting of autoimmune polyendocrine syndromes. A 38-year-old female presented with a 3 years history of secondary amenorrhea. She was on treatment for Hashimoto's thyroiditis and Addison's disease. The ovaries were cystic and histologically featured by folliculotropic lymphoplasmacytic inflammatory infiltrate concentrated in the theca interna layer of developing follicles, but sparing the primordial follicles.

Plasma protein and hormone profiles associated with autoimmune oophoritis and ovarian tumorigenesis in neonatally thymectomized mice.

Interactions between the immune and endocrine systems may have an important role in ovarian tumorigenesis. Neonatal thymectomy at 3 days of age (Tx-3) in (C3H/HeMs x 129/J)F1 (C31) female mice results in an autoimmune ovarian dysgenesis then subsequent tumor formation. At 3 months of age the histology of the ovaries showed that approximately 60% of the Tx-3 mice (Tx-3 DO) had completely lost their oocytes and follicles so that a preponderance of interstitial-like cells remained. The remainder of the Tx-3 mice had atypical ovaries (Tx-3 AO). The vaginal cytology showed that both groups of Tx-3 mice became acyclic at an early age compared to the intact mice. Around 12 months of age, a high percentage of the dysgenic ovaries developed trabecular tumors. Plasma protein-related indicators of systemic inflammatory responses showed little change during the course of the autoimmune oophoritis or ovarian tumorigenesis. Levels of estradiol 17 beta (E2) and testosterone (T) did not vary in the Tx-3 mice compared to those of the intact mice through 21 months of age but progesterone levels were lower during the exacerbation of the autoimmune oophoritis and tumor development. By 24 months of age levels of P increased while E2 decreased. Apparently, the premature reproductive failure in these mice at a young-adult stage results from the early loss of the oocytes by the localized autoimmune insult to the ovaries. The autoimmune oophoritis may then be the primary trigger for the subsequent ovarian tumor formation and the tumors succeed in association with the altered hormonal milieu.

Cytomegalovirus oophoritis: ovarian cortical necrosis.

Three of eight female patients with cytomegalovirus disease had evidence of ovarian infection at autopsy. All three patients with ovarian lesions were postmenopausal; the remaining five were premenopausal. The lesions, which may be bilateral and may occur without evidence of cytomegalovirus infection elsewhere, are distinctive macroscopically, pathognomonic microscopically, and characterized by acute focal ovarian cortical necrosis with numerous cytomegalic cells and a variable but usually severe inflammatory reaction. It is suggested that reduced ovarian cortical vascular perfusion reactivates a latent infection in cortical stromal cells. This elicits inflammatory necrosis and the characteristic morphological lesions. This previously unreported lesion is not likely to have clinical importance.

Aromatase activity in cultured ovaries from neonatally thymectomized mice with ovarian dysgenesis.

The autoimmune oophoritis resulting from thymectomy at 3 days of age (Tx-3) in B6A female mice is characterized by dysgenic ovaries and circulating auto-antibodies against the oocyte (AOA). Dysgenesis of the ovaries starts around 24 days of age with a decline in numbers of the oocytes and follicles and is accompanied by lymphocytic infiltration. By 60 days of age the ovarian dysgenesis (OD) is complete with a preponderance of interstitial cells associated with elevated levels of testosterone (T). From 60-120 days of age the ovaries become progressively smaller in size and T levels rise. Since ovarian interstitial cells can produce T, assessment of aromatase activity was determined using cultured ovaries from 20-, 30-, 60-, 90- and 120-day-old mice. Similar or enhanced ability in aromatizing T to estradiol-17 beta (E2) was demonstrated by the ovaries from all Tx-3 mice compared with those from intact mice. At 30 and 60 days of age Tx-3 mice had increased circulating levels of E2 then the levels of E2 returned to those of intact mice at 90 and 120 days of age. The results indicate that the ovaries in Tx-3 mice may have an ability to aromatize T to E2 in culture, but apparently are not doing so at 90 and 120 days of age in situ. Further, ovaries of Tx-3 animals are able to aromatize T to E2 in the absence of organized follicular cells. These abnormal responses of ovarian hormones clearly demonstrate that the presence of AOA have a damaging effect on the endocrine activity as well as the morphology of the ovary.

Autoimmune oophoritis.

A 43-year-old para 3 woman presented with a six-year history of progressive oligomenorrhea and hypomenorrhea. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed for the suspicion of ovarian cysts. On histologic examination, the ovaries contained lymphocytic and plasma cell infiltrates in relation to the theca interna of growing follicles, to the corpora lutea and to the endocrine hilar cells. The infiltrates increased in density with the follicular maturation and culminated against the corpora lutea. The plasma cell population was polyclonal. No antibodies to ovarian tissue components could be demonstrated in the patient's serum by means of immunohistochemistry; but antibodies to the zona glomerulosa of adrenal cortex were detected by serologic means. Although a rare disease, autoimmune oophoritis must be recognized histologically because it is a cause of ovarian failure and because it indicates that the patient is at risk of developing associated Addison's disease.

Autoimmune oophoritis. An incidental finding.

A case of autoimmune oophoritis is reported. A 41-year-old woman had a total abdominal hysterectomy and bilateral salpingo-oophorectomy for menorrhagia, polymenorrhoea and cystic ovaries. The diagnosis of autoimmune oophoritis was not suspected clinically, and was an unexpected histological finding in the ovaries. The gross and histological appearances of this rare condition are described, and the lymphoid infiltrate characterised by immunocytochemistry. Recognition of this condition by pathologists is important, as there is an associated risk of developing other autoimmune disease, even some years later, necessitating close patient follow-up. In this case serum auto-antibodies to adrenal cortex were detected, indicating a subsequent risk of Addison's disease.