Diminished ovarian reserve induced by chronic unpredictable stress in C57BL/6 mice

Abstract

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-Müllerian 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.

摘要

长期的心理压力被认为是卵巢储备减少（DOR）的重要原因。但是, 缺乏心理压力诱发的DOR动物模型。我们旨在验证8周慢性不可预测压力（CUS）模式对C57BL / 6小鼠卵巢储备和生殖激素分泌的影响。我们发现, 在CUS暴露8周后, CUS模型小鼠的原始卵泡、窦前卵泡以及黄体的数量显著减少。与对照组相比, 模型小鼠的血清卵泡刺激素、皮质酮水平更高, 而黄体生成素、雌二醇、雄激素和抗苗勒管激素水平更低。此外, 我们发现FSH受体和AMH蛋白在模型小鼠卵巢中被下调。尽管两组之间产仔数未发现明显差异, 但暴露于CUS 6周后, 模型组的卵巢储备量显著降低。这些结果证实了以下假设：我们采用的8周CUS模型可以诱导C57BL/6小鼠的DOR模型, 并可能对卵巢储备造成长期不利影响。因此, 我们的结果表明我们已经成功建立了心理应激诱导的DOR动物模型, 可用于进一步研究。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Ovarian reserve
• chronic unpredictable stress
• psychological stress
• ovarian follicles
• mice

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors extend their appreciation to Professor Kang Yu from Obstetrics and Gynecology Hospital of Fudan University for kindly providing with the mouse restrain device. This work was supported by the National Natural Science Foundation of China [no. 81273956] and the Science and Technology Commission of Shanghai Municipality [no.15401931800].