Recovery of suppressed male reproduction in mice exposed to progesterone during embryonic development by testosterone
Recovery of suppressed male reproduction in mice exposed to progesterone during embryonic development by testosterone
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DOI：
10.1530/rep-08-0438
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发表时间：
2009-03-01
期刊：
影响因子：
3.8
通讯作者：
Reddy, P. Sreenivasula
中科院分区：
文献类型：
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作者：
Harini, C.;Sainath, S. B.;Reddy, P. Sreenivasula
本研究的目的是检查是否经胎盘暴露于孕酮引起男性生殖异常，以及是否可以逆转睾酮管理后的变化。在妊娠第1、3和7天向小鼠注射孕酮。使雄性幼仔（F1代）生长50天，并评估生殖性能。孕激素暴露于孕酮（7 mg/kg体重）导致小鼠体重显著增加，生殖组织指数下降。实验小鼠的精子总数、活精子和活动精子减少。低渗肿胀试验显示实验小鼠精子膜完整性严重改变。与对照组相比，胚胎发育期间暴露于孕酮的小鼠睾丸类固醇生成标记酶（羟基-δ-5-类固醇脱氢酶、3 β-和类固醇δ-异构酶簇（HSD 3B）和羟基类固醇（17-β）脱氢酶1（HSD 17 B））的活性水平显著降低。在胚胎发育过程中，孕酮暴露的小鼠血清睾酮水平随着血清FSH和LH的升高而降低。孕激素的产前暴露导致精子数量的显着减少和曲细精管管腔的增加。与正常雌性同居的实验小鼠显示出生育能力下降。在出生后第20、30和40天给予暴露于孕酮的新生儿睾酮（4.16 mg/kg体重），可恢复孕酮诱导的雄性生殖抑制。这表明，在胚胎发育过程中暴露于孕酮的小鼠雄性生殖功能的损害可能是通过抑制睾酮的产生来介导的。这些结果还表明，在子宫内暴露于孕酮影响男性生殖和补充睾酮恢复男性生殖抑制。
The present study aimed to examine whether transplacental exposure to progesterone caused male reproductive abnormalities and whether the changes can be reversed after testosterone administration. Progesterone was injected to mice on day 1, 3, and 7 of pregnancy. The male pups (F1 generation) were allowed to grow for 50 days and assessed for reproductive performance. Gestational exposure to progesterone (7 mg/kg body weight) resulted in significant body weight gain with a decrease in reproductive tissue indices in mice. Total sperm count, viable sperm, and motile sperm decreased in experimental mice. Hypo-osmotic swelling test revealed that experimental mice sperm membrane integrity was severely altered. The activity levels of testicular steroidogenic marker enzymes (hydroxy-delta-5-steroid dehydrogenase, 3 beta-and steroid delta-isomerase cluster (HSD3B) and hydroxysteroid (17-beta) dehydrogenase 1 (HSD17B)) decreased significantly in mice exposed to progesterone during embryonic development when compared with the controls. The levels of serum testosterone decreased with an increase in serum FSH and LH in mice exposed to progesterone during embryonic development. Prenatal exposure to progesterone caused significant reduction in the number of spermatozoa and increase in the lumen of seminiferous tubule. The experimental mice that cohabited with normal females showed fertility reduction. Administration of testosterone (4.16 mg/kg body weight) on postnatal day 20, 30, and 40 to progesterone-exposed prenates resulted in recovery of progesterone-induced suppressed male reproduction. It is suggested that the impairment of male reproduction in mice exposed to progesterone during embryonic development could be mediated through the inhibition of testosterone production. These results also indicate that in utero exposure to progesterone affects male reproduction and that supplementation of testosterone restores the suppressed male reproduction.