Comparative study of DHEA and letrozole induced polycystic ovary syndrome in post-pubertal rats

Abstract

Aim

In order to select a suitable rat model for studying polycystic ovary syndrome (PCOS).

Methods

Post-pubertal Sprague Dawley (SD) rats were allocated to four groups, abbreviated as the control 1 group, DHEA subcutaneous injection (DHEA) group, control 2 group, letrozole intragastric injection (letrozole) group. Body weight and the estrous cycle were monitored during the modeling. Serum stress hormones and reproductive hormones were evaluated by ELISA. The uterus and ovaries were weighed, ovarian follicle counts were calculated, and AR, LHR, FSHR, and AMH expression were assessed by immunohistochemistry.

Results

In both model group subjected to the 30-day protocol of DHEA or letrozole, the mean body weights were significantly increased. Rats from both model group exhibited a significant increase of the mean length of the diestrous phase of the estrous cycle, the DHEA group had a longer diestrous phase. There was also a significant increase of serum T, E2, LH, insulin, and a significant decrease of AMH in both model group. There was a significant decrease of ovarian weight, P, and serum FSH, and a significant increase of uterus weight, serum LH/FSH in DHEA model group. There was no significant difference in serum P, FSH, and LH/FSH in letrozole model group. Both two model groups showed significantly higher AR, LHR, and AMH protein expression in rats’ ovaries. FSHR protein expression in DHEA group was lower, and in letrozole model group was not different.

Conclusion

Compared with letrozole intragastric injection group, the pathological characteristics of DHEA subcutaneous injection group rats were closer to the characteristics of PCOS.

摘要

目的：为多囊卵巢综合征（PCOS）的研究选择合适的大鼠模型。

方法：青春期后SD大鼠分为4组, 分别为对照1组、DHEA皮下注射组、对照2组、来曲唑胃内注射组。在建模过程中监测体重和发情周期。ELISA法检测血清应激激素和生殖激素水平。称重子宫和卵巢, 计算卵泡数, 并通过免疫组织化学评估AR、LHR、FSHR和AMH的表达。

结果：在接受DHEA或来曲唑30天方案的两个模型组中, 平均体重显著增加。两个模型组大鼠的发情间期平均长度均显著增加, DHEA组的发情间期更长。两个模型组的血清T、E2、LH、胰岛素水平均显著升高, AMH水平显著降低。DHEA模型组卵巢重量、P和血清FSH显著降低, 子宫重量、血清LH/FSH显著升高。来曲唑模型组血清P、FSH和LH/FSH无显著性差异。两个模型组大鼠卵巢中AR、LHR和AMH蛋白的表达均显著升高。DHEA组FSHR蛋白表达较低, 来曲唑模型组无差异。

结论：与来曲唑胃内注射组相比, DHEA皮下注射组大鼠的病理特征更接近PCOS的特征。

Keywords:

• Polycystic ovary syndrome (PCOS)
• animal models
• DHEA
• letrozole
• post-pubertal rats

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Shanghai University of Traditional Chinese Medicine [Grant Number 2016YSN50]; Shanghai Municipal Population and Family Planning Commission [Grant Number ZY3-JSFC-2-2019]; and Hospital Level [Grant Number 2019YYQ01]. The funders provide only financial aid, and there was no individuals employed or contracted by the funders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.