Chronic psychological stress has been considered to be a remarkable contributor to diminished ovarian reserve (DOR). However, there is a lack of a psychological stress-induced DOR animal model. We aim to validate the effects of an 8-week chronic unpredictable stress (CUS) paradigm on the ovarian reserve and reproductive hormone secretion of C57BL/6 mice. We found that after an 8-week CUS exposure, the numbers of primordial and preantral follicles and corpus luteum were significantly decreased in CUS model mice. Model mice also presented higher serum follicle-stimulating hormone, corticosterone levels and lower luteinizing hormone, estradiol, testosterone, anti-M€ ullerian hormone levels compared to those of control mice. Furthermore, we found that FSH receptor and AMH proteins were downregulated in model mouse ovaries. Although a significant litter size difference between the two groups was not found, the ovarian reserve remained significantly lower in the model group 6 weeks after CUS exposure. These results validated the hypothesis that the 8-week CUS paradigm that we adopted could induce the DOR phenotype in C57BL/6 mice and probably had a long-term adverse effect on ovarian reserve. Therefore, our results indicate that we have successfully established an animal model of psychological stress-induced DOR that can be used for further study.
The present study was designed to elucidate the underlying mechanisms of Bao Gui capsule (BGc) against hyperandrogenism, insulin resistance and leptin resistance of PcoS. letrozole was used to induce a PcoS model in rats, which were then randomly divided into four groups (n=9): control, Model, high-dose BGc (BGc-H) and low-dose BGc (BGc-l) group. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (lH), testosterone (T), estradiol (e 2 ), insulin, leptin, and interleukin (il)-1β, il-6 and tumor necrosis factor-α (TnF-α) in the hypothalamus were determined by eliSa. Protein levels of cytochrome P450c17α and cytochrome P450 aromatase (P450arom) in ovaries were determined by immunohistochemistry and western blot analysis. additionally, the expression of GluT4 in uterus and muscle tissue, and nF-κB, iKKβ and SocS3 mrna levels in the hypothalamus were evaluated. BGC significantly reduced body weight gain and decreased serum levels of lH/FSH, T, log T/e 2 , insulin and leptin compared with the PcoS model rats. Furthermore, BGc markedly reduced the expression of P450c17α and significantly increased the expression of P450arom in ovaries, and increased the expression of GluT4 in uterus and muscle tissues. BGc also effectively reduced the level of il-6 and TnF-α, and the expression of iKKβ, nF-κB and SocS3 in the hypothalamus of PcoS model rats. These results suggest that BGc may effectively improve hyperandrogenism, insulin resistance, endometrial receptivity and the low-grade chronic inflammation in the hypothalamus.
Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.