Chaiyu-Dixian Formula Exerts Protective Effects on Ovarian Follicular Abnormal Development in Chronic Unpredictable Mild Stress (CUMS) Rat Model

Abstract

Background: Chronic stress has been known to impair the female reproductive function, but the mechanism remains to be further investigated. Chaiyu-Dixian Formula (CYDXF) has been reported to regulate human endocrine disorders clinically. However, whether this formula can affect chronic stress-induced ovarian follicular development is not clear. Aim of the study:To examine effects of CYDXF on follicular development and explore possible mech anisms in a chronic unpredictable mild stress (CUMS) model.Materials and Methods: Adult female rats were randomly divided into 5 groups control group, CUMS group (saline treatment), CUMS+Estradiol (E 2 ) (0.1 mg/kg) group, CUMS +CYDXF (2.73 g/kg) group, and CUMS+CYDXF (5.46 g/kg) group. Body weights and behavioral tests were documented. Serum hormone levels were determined by enzymelinked immunosorbent assay (ELISA). Western blotting was used to detect the protein levels in the PI3K/Akt pathway and brain-derived neurotrophic factor (BDNF). The follicles were analyzed and classified according to their morphological characterization.Results: CYDXF relieved depression-like behaviors and ameliorated the abnormality in rat estrous cycle within the rat model of CUMS. Moreover, CYDXF could regulate endocrine disorders, increase the proportion of antral follicles as well as decrease the proportion of follicular atresia, which suggested that CYDXF could alleviate abnormal follicular development and improve overall ovarian function. Furthermore, CYDXF also activated the BDNF-mediated PI3K/Akt signaling pathway.Conclusions: CYDXF (at dose of both 2.73 and 5.46 g/kg) attenuated chronic stressinduced abnormal ovarian follicular development by relieving depression-like behaviors and improving ovarian function through partly the regulation of the BDNF-mediated PI3K/ Akt pathway.

The role of oxidative stress in ovarian aging: a review

“…[ 125 , 126 ]. In addition, pressure has been found to decrease levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) [ 127 , 128 ]; thus leading to over-activation of the sympathetic nerves in the ovary, thereby impairing ovarian function [ 129 ].…”

Chronic unpredictable mild stress-induced mouse ovarian insufficiency by interrupting lipid homeostasis in the ovary

“…It is known to have a negative impact on a person’s physical and mental health by interfering with the proper functioning of numerous systems, including the reproductive system. Several research studies have been conducted with the goal of developing an animal model for evaluating the relationship between chronic stress and early ovarian insufficiency (ovarian insufficiency) ( Fu et al, 2018 ; Fu et al, 2020 ; Xu et al, 2020 ). Although similar to the aforementioned studies, the CUMS method was developed in a mouse model to evaluate the impact of psychological stress on ovary follicle development in this study.…”

“…It was reported that the numbers of primordial follicles ( p < 0.05) and preantral follicles (primary follicle, p < 0.01; secondary follicle, p < 0.05) were significantly lower in the chronic unpredictable stress group ( Gao et al, 2020 ). Numerous researchers have found a link between female primary ovarian insufficiency (POI) and psychological stress, as previously mentioned ( Xu et al, 2020 ; Li et al, 2021 ).…”

Review of psychological stress on oocyte and early embryonic development in female mice

“…Rat studies revealed that psychological stress decreased the number of secondary and antral follicles [49]. Rats in the CUMS groups showed irregular oestrous cycles caused by marked changes in the antral follicles and atretic follicles, which was partly attributed to BDNF-mediated PI3K/ Akt pathway regulation [50]. Interestingly, more cystic follicles were found in the ovaries after similar psychological stress lasted for 12 weeks, suggesting that psychological stress may lead to polycystic ovary (PCO) [51].…”