The Effects of Vit E and Vit C Use on Ovarian Surface Epithelium and Follicle Reserve in Autologous Intraperitoneal Ovarian Transplantation in Rats: An Experimental Study

Purpose: The aim of this study was to investigate the effects of vitamin E (Vit E) and vitamin C (Vit C) on oxidant-antioxidant system markers, ovarian follicle reserves, and surface epithelium in autologous intraperitoneal ovarian transplantation in rats.Materials and Methods: 20 adult female Wistar Albino were randomly divided into four groups. Group 1 (n = 5), the control group, only had their abdomens opened and closed. Group 2 (n = 5): underwent an ovarian transplantation. Group 3 (n = 5) received 20 mg/kg of intraperitoneal (IP) Vit E 15 minutes before an ovarian transplantation. Group 4 (n = 5) received 50 mg/kg of IP Vit C that was administered 15 minutes before an ovarian transplantation.Vaginal cytology was performed to monitor the oestrus phase. Biochemically, tissue and serum malondialdehyde levels and erythrocyte superoxide dismutase (SOD) levels were measured. Histopathologically, the number dysplastic changes in the ovarian surface epithelium were examined. Results: Dysplastic changes in the surface epithelium of Group 2 were found to be significantly higher than in Group 1 and 4 (p < 0.02). In Group 2, the ovarian follicle reserves were significantly lower than in other groups (p < 0.02). In addition, a significant decrease in SOD levels was found in Group 2 compared to other groups (p < 0.02). Conclusion: The study showed that Vit E and Vit C in autologous intraperitoneal ovarian transplantation preserved the ovarian follicle reserve. Vit C was found to be more effective than Vit E.

Selective YAP activation in Procr cells is essential for ovarian stem/progenitor expansion and epithelium repair

Ovarian surface epithelium (OSE) undergoes recurring ovulatory rupture and OSE stem cells rapidly generate new cells for the repair. How the stem cell senses the rupture and promptly turns on proliferation is unclear. Our previous study has identified that Protein C Receptor (Procr) marks OSE progenitors. In this study, we observed decreased adherent junction and selective activation of YAP signaling in Procr progenitors at OSE rupture site. OSE repair is impeded upon deletion of Yap in these progenitors. Interestingly, Procr+ progenitors show lower expression of Vgll4, an antagonist of YAP signaling. Overexpression of Vgll4 in Procr+ cells hampers OSE repair and progenitor proliferation, indicating that selective low Vgll4 expression in Procr+ progenitors is critical for OSE repair. In addition, YAP activation promotes transcription of the OSE stemness gene Procr. The combination of increased cell division and Procr expression leads to expansion of Procr+ progenitors surrounding the rupture site. These results illustrate a YAP-dependent mechanism by which the stem/progenitor cells recognize the ovulatory rupture, and rapidly multiply their numbers, highlighting a YAP-induced stem cell expansion strategy.

Ameliorative Potential of Aqueous Extract of Broccoli Sprouts Against Triazophos Induced Ovarian Toxicity in Wistar Rats

Traditional therapeutic procedures using antioxidant-rich fruits and vegetables have been in vogue for the development of evidence-based biomarkers for assessing reproductive health. Present investigation was designed to study the antioxidative potential of broccoli sprouts aqueous extract (BE), against ovarian toxicity in female rats induced by triazophos (TZ). In the experimental setup, six groups of rats were formed; Control (group 1), BE (group 2), TZ (group 3), and also BE+TZ groups such as BE1 (group 4), BE2 (group 5) and BE3 (group 6) groups. Body weight was weekly recorded of all the rats, while vaginal smear was observed daily during 30 days experiment. After sacrifice, oxidative stress (OS) biomarkers levels viz; catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and lipid peroxidation (LPO) were determined along with histopathological and apoptotic observation. Results revealed differentially modified changes in OS biomarkers as CAT, SOD, GR, GPx, and GST, while LPO levels were significantly improved with broccoli supplementation compared to TZ group rats. Plasma progesterone and estradiol levels were also restored along with improved ovarian histoarchitecture among all BE+TZ treated rats. Reduced apoptotic granulosa cells with reduced atresia and normal ovarian surface epithelium height were also observed with BE treatment. BE exerts multi-mechanistic protective effects against TZ induced ovarian toxicity which is attributable to its antioxidant and protective actions.

Ovarian Cancer Tumour Biology: Genesis

Ovarian cancer (OC) is the fifth leading cause of cancer deaths among women, thus early diagnosis is of paramount importance to survival. A clear OC etiopathogenesis is not yet fully understood. Large histopathological variability predicts more initial tissue for carcinogenesis. Many connections of biologically different tissue as locus minoris resistentiae for carcinogenesis have been confirmed. Expansion of knowledge about OC etiopathogenesis may help to construct an algorithm for early diagnosis. Ovarian surface epithelium, ectopic Müllerian epithelium, and fallopian tubes, along with endometriosis, are significant in the process of OC development. An oxidative microenvironment caused by recurrent ovulation or arising due to a degradative process in ectopic endometrium, mainly endometriomas, play a prominent role in the development of OC.

Isolation and Characterization of Mesenchymal Stem Cells from Canine Ovarian Surface Epithelium

Background: Few studies have confirmed the presence of ovarian tissue stem cells indicating the capacity for differentiation. Based on this fact, it was hypothesized that mesenchymal stem cells (MSC) were found in ovarian surface epithelium (OSE) of canines that could easily be isolated. Methods: Both left and right ovaries were minced and digested using collagenase to obtain a stromal vascular fraction (SVF). MSCs were characterized using RT-PCR. To ascertain the trilineage differentiation potential, MSCs were stained with respective stain for osteocytes, chondrocytes and adipocytes. Result: We observed elongated, spindle-shaped and fibroblast like appearance of cells after 72 h of initial culture. Expression of MSC specific surface markers were observed through RT-PCR. Using Stem Pro® differentiation medium, OSE were differentiated into osteogenic, chondrogenic and adipogenic lineages and were found to be potential source for isolation, characterization and differentiation of MSCs. Canine (OSE) is easily accessible, multipotent and has high plasticity, holding promise for applications in regenerative medicine.

Integration of mouse ovary morphogenesis with developmental dynamics of the oviduct, ovarian ligaments, and rete ovarii.

The morphogenetic events that occur during fetal development of the mammalian ovary are crucial to the establishment of adult female fertility. While our knowledge of the cellular and molecular aspects of ovary development is increasing, the structural rearrangements that give rise to the cortex and medulla and the relation of other female reproductive tissues to the ovary have not been thoroughly investigated. In this study, we used tissue clearing and lightsheet microscopy to investigate the stepwise morphogenesis of the ovary. We found that the ovary transitioned from an elongated to a crescent-shaped structure, suggestive of a folding mechanism. As this occured, the ovarian surface epithelium wrapped from the ventral to the dorsal side of the ovary, forming the ovarian cortex and engulfing the dorsal face of the ovary to form the medulla. To identify the tissue mechanics that drive ovary folding, we investigated proximate tissues closely associated with the ovary including the M&uumlllerian duct, the cranial suspensory ligament, and the rete ovarii. We found that relocation of the M&uumlllerian duct to the ventral aspect of the ovary was associated with expansion of mesonephric tissue that left the ovary fully encapsulated by birth. The cranial suspensory ligament, which tethers the ovary to the body wall and to the M&uumlllerian duct may exert mechanical tension that triggers ovarian folding. Finally, we found that the rete ovarii, a previously dismissed epithelial appendage of the ovary, significantly expanded during late gestation and may act to anchor the ovary to the mesonephros, leading to integration of extrinsic components into the ovarian medulla. This detailed atlas of ovary morphogenesis reveals novel relationships among the ovary and its surrounding tissues and paves the way towards the functional investigation of the relationship between architecture and differentiation of the mammalian ovary.

Mechanisms of High-Grade Serous Carcinogenesis in the Fallopian Tube and Ovary: Current Hypotheses, Etiologic Factors, and Molecular Alterations

Ovarian high-grade serous carcinomas (HGSCs) are a heterogeneous group of diseases. They include fallopian-tube-epithelium (FTE)-derived and ovarian-surface-epithelium (OSE)-derived tumors. The risk/protective factors suggest that the etiology of HGSCs is multifactorial. Inflammation caused by ovulation and retrograde bleeding may play a major role. HGSCs are among the most genetically altered cancers, and TP53 mutations are ubiquitous. Key driving events other than TP53 mutations include homologous recombination (HR) deficiency, such as BRCA 1/2 dysfunction, and activation of the CCNE1 pathway. HR deficiency and the CCNE1 amplification appear to be mutually exclusive. Intratumor heterogeneity resulting from genomic instability can be observed at the early stage of tumorigenesis. In this review, I discuss current carcinogenic hypotheses, sites of origin, etiologic factors, and molecular alterations of HGSCs.

Effects of coenzyme Q10 on ovarian surface epithelium-derived ovarian stem cells and ovarian function in a 4-vinylcyclohexene diepoxide-induced murine model of ovarian failure

Background Several studies have shown that coenzyme Q10 (CoQ10) can rescue ovarian aging and that ovarian surface epithelium (OSE)-derived ovarian stem cells (OSCs) are useful for treating infertility due to ovarian aging. However, few studies have examined the effect of CoQ10 on OSCs. This study was aimed to investigate whether CoQ10 activates OSCs and recovers ovarian function in a 4-vinylcyclohexene diepoxide (VCD)-induced mouse model of ovarian failure. Methods Forty female C57BL/6 mice aged 6 weeks were randomly divided into four groups (n = 10/group): a control group administered saline orally, a CoQ10 group administered 150 mg/kg/day of CoQ10 orally in 1 mL of saline daily for 14 days, a VCD group administered 160 mg/kg/day of VCD i.p. in 2.5 mL of saline/kg for 5 days, and a VCD + CoQ10 group administered VCD i.p. for 5 days injection and CoQ10 (150 mg/kg/day) orally for 14 days. After treatment, follicle counts were evaluated by hematoxylin and eosin (H&E) staining, and ovarian mRNA expressions of Bmp-15, Gdf-9, and c-Kit were examined by quantitative real-time PCR. Serum FSH, AMH, and ROS levels were also measured. Oocyte-like structure counts and the expressions of Oct-4 and MVH were also evaluated after culturing OSE for 3 weeks. In a second experiment, 32 female mice were administered CoQ10 as described above, induced to superovulate using PMSG and hCG, and mated. Numbers of zygotes and embryo development rate were examined. Results Postcultured OSE showed significant increases in the numbers of oocyte-like structure and that the expression of Oct-4 and MVH were higher in the VCD + CoQ10 group than in the VCD group (p < 0.05). Numbers of surviving follicles from primordial to antral follicles, numbers of zygotes retrieved and embryo development rate to blastocyst were significantly greater in the VCD + CoQ10 group than in the VCD group (p < 0.01). Serum AMH level and ovarian expressions of Bmp-15, Gdf-9 and c-Kit were also significantly greater in the VCD + CoQ10 group than in the VCD group (p < 0.05). In contrast, serum ROS level was significantly lower in the VCD + CoQ10 group than in the VCD group (p < 0.05). Conclusion This study shows that CoQ10 stimulates the differentiation of OSE-derived OSCs and confirms that CoQ10 can reduce ROS levels and improve ovarian function and oocyte quality in mice with VCD-induced ovarian failure.

Effects of Coenzyme Q10 on Ovarian Surface Epithelium-derived Ovarian Stem Cells and Ovarian Function in 4-vinylcyclohexene Diepoxide-induced Ovarian Failure Mice.

Background: Several studies have shown that CoQ10 can rescue ovarian aging and that ovarian surface epithelium (OSE)-derived ovarian stem cells (OSCs) are useful for treating infertility with ovarian aging. However, there are few studies the effect of CoQ10 on OSCs. This study was aimed to investigate whether CoQ10 activates OSCs while recovering ovarian function using 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure mouse model.Methods: C57BL/6 female mice aged 6 weeks were randomly divided into four groups (n=10/group): (Control) saline and orally, (CoQ10) 150 mg/kg/day orally in 1 mL of saline daily for 14 days, (VCD) 160 mg/kg/day, 2.5 ml/kg ip for 5 days, (VCD+CoQ10) 5 days after VCD injection, CoQ10 (150 mg/kg/day) orally for 14 days. After final treatment of CoQ10, follicle counts were evaluated by hematoxylin and eosin (H&E) staining, and ovarian mRNA expressions of Bmp-15, Gdf-9, and c-Kit were examined by quantitative real-time PCR. Serum FSH, AMH, and ROS levels were also measured. Oocyte-like structure count and expression of Oct-4 and MVH were evaluated from postcultured OSE for 3 weeks. In the second experiment, another 32 female mice were administered with CoQ10 in the same way as above and were superovulated by PMSG and hCG, followed by mated with males. Then, numbers of zygotes ovulated and embryo development rate were examined. Results: Postcultured OSE had significantly increased numbers of oocyte-like structure and expression of Oct-4 and MVH in VCD+CoQ10 group compared to VCD group (p <0.05). Numbers of surviving follicles including from primordial to antral follicles, numbers of zygotes retrieved and embryo development rate to blastocyst were significantly higher in VCD+CoQ10 group compared to VCD group (p <0.01). Serum AMH level and ovarian expression of Bmp-15, Gdf-9, and c-Kit were significantly increased in VCD+CoQ10 group compared to VCD group (p <0.05). In contrast, serum ROS level was significantly decreased in VCD+CoQ10 group compared to VCD group (p <0.05). Conclusion(s): This is the first study to show that CoQ10 stimulates the differentiation of OSE-derived OSCs. Also this study confirms that CoQ10 can reduce ROS levels, leading to improve ovarian function and oocyte quality in ovarian failure mice.

Ultrastructural evaluation of oocytes during fluorosis in rat ovarian follicles

Fluoride is a well-known environmental pollutant and its effect on human health has long been of interest to biomedical researchers. Various studies have shown that fluoride causes adverse effects on the fertility. Wistar albino female rats weighing 150-200 g were randomly divided into six rats in each group. The rats in experimental groups treated with 300 and 600 mg NaF/kg bw/day by oral gavage for 40 days. The present investigation focuses on the ovary of rat treated with sodium fluoride and its amelioration by curcumin. The results revealed that the sodium fluoride exposure to female rats treated with 300 mg NaF/kg bw/day, the surface epithelium had less number of ruffles and blebs of the plasma membrane. There was abrasion of ovarian surface epithelium. In rats treated with 600 mg/kg bw/day NaF, the cuboidal shape of the surface epithelium were changed into elongated appearance. The cells were devoid of microvilli, blebs and ruffles. After administration of curcumin, many follicles in different stages of development were visible. The ovarian surface epithelium showed normal surface epithelium with improvement in the shape of cuboidal cells.