Reproduction Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
PLoS One. 2013 Aug 15;8(8):e71705. doi: 10.1371/journal.pone.0071705. eCollection 2013.
The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (p< 0.01), the other effects were not observed in the offspring of experimental group ІІ. In summary, our data show that prenatal exposure of male rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.
生殖系统对外界环境刺激非常敏感，例如在妊娠发育和分化过程中外源类固醇。在雌性动物模型的产前生活中实验性诱导雄激素过多会重新编程其生殖生理学，然而雄激素过多对雄性生殖系统的胎儿编程尚未得到很好的研究。我们旨在使用大鼠模型确定在不同妊娠天数对雄性生殖系统进行两种不同剂量的睾酮产前暴露的影响。16 只怀孕大鼠随机分为两组实验组和两组对照组。实验组І 在妊娠第 16-19 天每天皮下注射 3 毫克游离睾酮，其对照物在此期间接受溶剂；实验组П 在妊娠第 20 天每天皮下注射 20 毫克游离睾酮，其对照物同时接受溶剂。这些研究组的 32 只雄性后代的生殖系统形态和功能在 6-30-60 天龄和青春期后进行了比较。与对照组相比，两组实验雄性后代的肛门生殖器距离在不同测量日没有显著差异。在实验组І 的后代中，睾丸重量、Sertoli 细胞、精母细胞和精子细胞数量、精子计数和活力以及青春期后的血清睾酮浓度均显著降低；除了精子活力降低（p<0.01）外，实验组ІІ 的后代未观察到其他影响。总之，我们的数据表明，雄性大鼠胎儿在产前暴露于过量睾酮会破坏生殖功能，这种作用高度依赖于暴露的时间、持续时间和水平。在胎儿期暴露于高水平雄激素的个体中，生殖系统似乎应该在青春期进行评估，并且可能需要治疗。
