Toluene Can Disrupt Rat Ovarian Follicullogenesis and Steroidogenesis and Induce Both Autophagy and Apoptosis

Toluene has been shown to be highly toxic to humans and animals and can cause damage to various tissues. However, studies reporting its effects on ovarian function are still limited. In this study, we investigated the in vivo effect of toluene using female Wistar rats. We found that toluene exposure decreased ovarian weight and affected ovarian structure by increasing the number of abnormally growing follicles. Moreover, it significantly increased progesterone and testosterone levels. We also showed that toluene exposure decreased GDF-9 protein and its encoding gene. In addition, it inhibited the expression of most of the genes involved in granulosa cell proliferation and differentiation, such as Insl3, ccnd2 and actb. The TUNEL assay showed that apoptosis occurred at the middle and high doses only (4000 and 8000 ppm, respectively), whereas no effect was observed at the low dose (2000 ppm). Interestingly, we showed that toluene exposure induced autophagy as LC3 protein and its encoding gene significantly increased for all doses of treatment. These results may suggest that the activation of autophagy at a low dose of exposure was to protect ovarian cells against death by inhibiting apoptosis, whereas its activation at high doses of exposure triggered apoptosis leading to cell death.

Zika virus infection in the ovary induces continuously elevated progesterone level and compromises conception in interferon α/β receptor-deficient mice

Zika virus (ZIKV) belongs to mosquito-borne flaviviruses. Unlike other members in the family, ZIKV can be sexually transmitted, and the female genital tracts are susceptible to ZIKV. However, the impacts of ZIKV infection on nonpregnant female reproductive health are not understood. In this study, we investigated the effects of ZIKV infection on the ovary by using nonpregnant female interferon α/β receptor-deficient ( Ifnar1 -/- ) mice. The results showed that the ovary supported ZIKV replication, and the granulosa and theca cells of antral follicles were susceptible. ZIKV replication in situ significantly reduced the numbers of antral follicles, aggravated follicular atresia and disrupted folliculogenesis. Notably, ZIKV replication in the ovary caused disordered ovarian steroidogenesis manifested by decreased expression of key enzymes linked to sex hormone synthesis including the cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1). Further, we observed that ZIKV infection disrupted the estrous cycle, and thus prolonged the time to conceive. More importantly, although ZIKV RNA could not be detected at 3 months post infection, the damaged ovarian structure and dysfunction were also observed. Taken together, our study demonstrates that ZIKV infection in nonpregnant female mice cause ovarian damage and dysfunction, even long after ZIKV clearance. These data provide important information to understand the effects of ZIKV infection in female reproductive tissues and basic evidence for further studies. IMPORTANCE ZIKV, a flavivirus, is primarily transmitted by mosquito bites. But it can also be transmitted vertically and sexually. Although ZIKV-associated Guillain-Barre syndrome and microcephaly have drawn great attention, there have been few studies on the potential effects of ZIKV on genital tract of non-pregnant female. This study investigated the effects of ZIKV on the ovary in mice. We found that ZIKV replicated in the ovary and the granulosa and theca cells of antral follicles were susceptible. ZIKV replication in situ significantly damaged ovarian structure and function, and disrupted folliculogenesis. Notably, ZIKV infection further disrupted the estrous cycle and prolonged the time to conceive in mice by causing disordered ovarian steroidogenesis. These effects were observed in both the acute phase and the recovery phase after viral elimination. Overall, the new findings provide important additions to make out the potential adverse impacts of ZIKV on reproductive health in females.

EFFECTS OF HIGH-FREQUENCY SURGICAL ENERGY ON OVARIAN STRUCTURE IN TOTAL TUBAL HYSTERECTOMY

На современном этапе развития медицины, не смотря на разработку эффективных препаратов, основным методом лечения доброкачественных заболеваний матки, является хирургический. Качество жизни пациенток, перенесших гистерэктомию, является важным критерием оценки эффективности проведенного лечения, значительное внимание исследователей уделяется вопросу оценки функционального состояния сохраненных после гистерэктомии яичников. В современной клинической медицине при выполнении оперативных вмешательств широко используются высокочастотные хирургические энергии, но изучение их влияния на ткани не завершено. Мы проанализировали опубликованные результаты исследований по интересующей нас проблеме. The question of the condition of the ovaries after a hysterectomy with simultaneous removal of the fallopian tubes remains unresolved. According to some authors, the ovarian function does not change, while others provide evidence of decreased ovarian function. The effect of the applied electrocoagulation on ovarian function is also still being studied. This article presents the results of our published studies concerning the function of the ovaries after hysterectomy, including simultaneous bilateral hysterectomy. After reviewing the available studies, we concluded that it is necessary to conduct an experimental study in order to study the morphological changes in the ovaries after the use of high-frequency surgical energy used in hysterectomy with fallopian tubes.

Dietary Protein Deficiency in Early Life of F1 and F2 Generations of Sprague Dawley Rats Disrupts the Reproductive Function

Background: The ability to reproduce efficiently is an important characteristic that has evolved through natural selection. Nutrition can modulate reproductive activities at different levels, its effect on nutrition is therefore complex and less predictable. This study aims at investigating the underlying effect of persistent dietary protein deficiency during early life on reproductive parameters of subsequent (F1 and F2) generations.Method: Rats in group of four (4) were fed daily, with different ration of protein diet (PD) formulated as: 21% protein diet, 10%protein diet, 5%protein diet and control diet (rat chow, containing 16-18% protein). They were fed ad libitum before mating, throughout gestation and lactation, and next generations were weaned to the maternal diet. Reproductive function analysis (which include; gestation and pubertal hormonal profiling, onset of puberty, oestrus cyclicity, sexual response) and morphometric analysis of the ovarian structure were carried out to assess associated consequences.Results: showed significant reduction in the fertility index as a consequence of altered reproductive function in the protein deficient models at P≤ 0.05. Low protein diet posed suboptimal intrauterine condition, which was linked to increased prenatal morbidity and mortality, lowered birthweight delayed onset of puberty, induced cycle irregularity, altered follicular maturation and endocrine dysfunction in the protein deficient groups. Reproductive status of an individual female organism critically depends on the maintenance of ovarian structure and function that has been associated with the hypothalamic pituitary-gonadal axis, hormonal events and sexual maturity.Conclusion: There is therefore an association between persistent early life protein deficiency and reproductive response which mechanistically involves life-long changes in key ovarian cytoarchitecture and function.

HISTOLOGY AND HISTOMORPHOMETRY OF GAYO MARE OVARIES

This study aims to determine the histology, the number and diameter of follicles, and the corpus albican of the Gayo mare ovary. The micro technical process was applied to 3 pairs of ovarian samples for further hematoxylin-eosin (HE) staining. Observation of ovarian structure was carried out microscopically and the data were analyzed statistically. The results showed that the Gayo mare ovary consists of the medulla on the outside and the cortex on the inside. Medulla consists of small follicles, blood vessels, nerves, and connective tissue. Meanwhile, the cortex consists of de Graff's follicle, corpus luteum, corpus albican, and ovulatory fossa. Follicles are composed of oocytes, granulosa cells, internal and external theca cells, oophorous cumulus, follicular antrum, and follicular fluid. Atretic follicles contain lutein cells that have been damaged. The corpus luteum is composed of granulosa lutein tissue, internal theca and external. The corpus albican is composed of scar tissue and lutein cells. The measurement results showed that the primordial follicle diameter was 26.60±2.37 µm, primary follicle 54.33±6.70 µm, secondary follicle 119.32±25.55 µm, tertiary follicle 250.86±49.46 µm, atretic follicle 49.03±45.47 µm, the corpus albican 511.10±132.41 µm. Thus, it can be concluded that the Gayo mare ovary has a histological structure that is not different from the ovary of other mares. Follicular growth occurs in the medulla of the ovary, and de Graff's follicles are present in the cortex of the ovaries.

The Roles of Different Stem Cells in Premature Ovarian Failure

Premature ovarian failure (POF) is characterized by amenorrhea, hypergonadotropism and hypoestrogenism before the age of 40, which affects 1% of women in the general population. POF is complex and heterogeneous due to its pathogenetic mechanisms. It is one of the significant causes of female infertility. Although many treatments are available for POF, these therapies are less efficient and trigger many side effects. Therefore, to find effective therapeutics for POF is urgently required. Due to stem cells having self-renewal and regeneration potential, they may be effective for the treatment of ovarian failure and consequently infertility. Recent studies have found that stem cells therapy may be able to restore the ovarian structure and function in animal models of POF and provide an effective treatment method. The present review summarizes the biological roles and the possible signaling mechanisms of the different stem cells in POF ovary. Further study on the precise mechanisms of stem cells on POF may provide novel insights into the female reproduction, which not only enhances the understanding of the physiological roles but also supports effective therapy for recovering ovarian functions against infertility.

Mechanism and Effect of UCMSCS on Ovarian Structure and Function in Naturally Ageing C57 Mice

Background: The ovary is the core reproductive organ of a woman and is of great significance for maintaining normal functioning of the reproductive system and the stability of the endocrine system. With an increase in age, the ovaries begin to age, and ovarian ageing will cause a decline in fertility. Methods: Ageing C57 mice were used to explore the mechanism by which mouse umbilical cord mesenchymal stem cells (mUCMSCs) promote the antioxidant repair of granulocytes (mGCs). The ovarian volume in C57 mice, which were routinely reared to 18 months, decreased, and the follicles at all levels disappeared. All statistical analyses were performed using SPSS 21.0 statistical software. P <0.05 was considered to indicate a significant difference. Results: After mUCMSC transplantation, the mouse ovaries increased in size, follicles at various levels were seen in the cortex, and sinus follicle counts increased, indicating that mUCMSCs have a curative effect on ovarian ageing. Conclusions: mUCMSCs downregulated the expression of apoptosis-related genes (Bax, Caspase-3), upregulated the expression of SOD2 and the peroxidase gene PRDX IV, and reduced the granulocyte apoptosis rate and ROS level. Co-cultivation with mUCMSCs can increase antioxidative stress in mGCs and reduce mGC apoptosis.

Apocynin Dietary Supplementation Delays Mouse Ovarian Ageing

Advanced maternal age is associated with higher infertility rates, pregnancy-associated complications, and progeny health issues. The ovary is considered the main responsible for these consequences due to a continuous decay in follicle number and oocyte quality. Intracellular imbalance between oxidant molecules and antioxidant mechanisms, in favour of the former, results in oxidative stress (OS) that is believed to contribute to ovarian ageing. This work is aimed at evaluating whether an age-related increase in ovarian OS, inflammation, and fibrosis may contribute to tissue dysfunction and whether specific antioxidant supplementation with a NADPH oxidase inhibitor (apocynin) could ameliorate them. Mice aged 8–12 weeks (reproductively young) or 38-42 weeks (reproductively aged) were employed. Aged mice were divided into two groups, with one receiving apocynin (5 mM) in the drinking water, for 7 weeks, upon which animals were sacrificed and their ovaries collected. Ovarian structure was similar at both ages, but the ovaries from reproductively aged mice exhibited lipofuscin deposition, enhanced fibrosis, and a significant age-related reduction in primordial and primary follicle number when compared to younger animals. Protein carbonylation and nitration, and markers of OS were significantly increased with age. Moreover, mRNA levels of inflammation markers, collagens, metalloproteinases (MMPs), and tissue inhibitor MMPs (TIMPs) were upregulated. Expression of the antifibrotic miRNA29c-3p was significantly reduced. Apocynin supplementation ameliorated most of the age-related observed changes, sometimes to values similar to those observed in young females. These findings indicate that there is an age-related increase in OS that plays an important role in enhancing inflammation and collagen deposition, contributing to a decline in female fertility. Apocynin supplementation suggests that the imbalance can be ameliorated and thus delay ovarian ageing harmful effects.