Ramezani Tehrani Fahimeh, Noroozzadeh Mahsa, Zahediasl Saleh, Piryaei Abbas, Hashemi Somayeh, Azizi Fereidoun
Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
Int J Endocrinol Metab. 2014 Apr 1;12(2):e16502. doi: 10.5812/ijem.16502. eCollection 2014 Apr.
Polycystic ovary syndrome (PCOS) is one of the most common reproductive disorders in women. Previous studies have shown that prenatal exposure of female fetuses to androgen can be considered an important factor in the development of PCOS.
In the present study we aimed to examine the effects of prenatal exposure of female rat fetuses to previously documented doses of testosterone on different embryonic days on the development of PCOS phenotype in adulthood.
Pregnant rats were divided into four groups, experimental and control groups. Three mg of free testosterone was administered subcutaneously to experimental group 1 on gestational days 16-19, daily and 20 mg on day 20, to experimental group 2, and the controls received solvent at the same times. Female offspring of these mothers aged between 90-100 days were examined for development and function of the reproductive system. Independent-sample student t test was used to compare the results between the experimental groups and controls.
Anogenital distance (P < 0.001) and clitoris length were significantly increased in the offspring of both experimental groups (P < 0.001 and P < 0.05 respectively). Nipples were not formed in the offspring of experimental group 1, whereas in experimental group 2 the number of nipples was unchanged. Vaginal length was significantly decreased in the offspring of experimental group 1 (P < 0.001), whereas in experimental group 2, no significant difference was observed. In the offspring of experimental group 1, hormonal profiles did not differ, but in experimental group 2, levels of testosterone (P < 0.05) and LH (P < 0.01) were significantly increased, but estrogen (P < 0.05) and anti-Mullerian hormone levels (P < 0.001) were significantly decreased. A significant increase in the number of preantral and antral follicles was observed in the ovaries of offspring of experimental group 1 (P < 0.05); whereas there was no such a difference in experimental group 2.
The time of prenatal exposure to androgens may have a significant role in the development of PCOS. Increased prenatal androgen levels are associated with hormonal changes and morphological disorders of the reproductive system. Therefore, avoiding exposure to androgen excess during critical periods of fetal development may prevent or reduce adulthood PCOS manifestations caused by prenatal excess androgen.
多囊卵巢综合征（PCOS）是女性最常见的生殖系统疾病之一。既往研究表明，雌性胎儿在产前暴露于雄激素可被视为PCOS发病的一个重要因素。
在本研究中，我们旨在探究雌性大鼠胎儿在胚胎发育不同阶段，经皮下注射已记录剂量的睾酮后，对成年期PCOS表型发育的影响。
将怀孕大鼠分为四组，即实验组和对照组。实验组1在妊娠第16 - 19天每天皮下注射3mg游离睾酮，在第20天注射20mg；实验组2在妊娠第20天皮下注射20mg游离睾酮；对照组在相应时间注射溶剂。对这些母亲90 - 100日龄的雌性后代进行生殖系统发育及功能检查。采用独立样本t检验比较实验组和对照组的结果。
两个实验组后代的肛殖距（P < 0.001）和阴蒂长度均显著增加（分别为P < 0.001和P < 0.05）。实验组1后代未形成乳头，而实验组2后代乳头数量未变。实验组1后代阴道长度显著缩短（P < 0.001），而实验组2后代未观察到显著差异。实验组1后代激素水平无差异，但实验组2后代睾酮水平（P < 0.05）和促黄体生成素（LH）水平（P < 0.01）显著升高，而雌激素水平（P < 0.05）和抗苗勒管激素水平（P < 0.001）显著降低。实验组1后代卵巢中窦前卵泡和窦卵泡数量显著增加（P < 0.05）；而实验组2未观察到这种差异。
产前暴露于雄激素的时间可能在PCOS的发生发展中起重要作用。产前雄激素水平升高与生殖系统的激素变化和形态紊乱有关。因此，在胎儿发育的关键时期避免暴露于过量雄激素，可能预防或减少产前雄激素过量导致的成年期PCOS表现。
