Brief maternal exposure of rats to the xenobiotics dibutyl phthalate or diethylstilbestrol alters adult-type Leydig cell development in male offspring
Brief maternal exposure of rats to the xenobiotics dibutyl phthalate or diethylstilbestrol alters adult-type Leydig cell development in male offspring
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DOI：
10.1038/aja.2012.138
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Anand-Ivell, Ravinder
中科院分区：
文献类型：
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作者：
Ivell, Richard;Heng, Kee;Anand-Ivell, Ravinder
母体暴露于雌激素性异生物质或邻苯二甲酸酯与早期男性生殖发育的扭曲有关，在人类中称为睾丸发育不全综合征。然而，尚不清楚这种早期妊娠和/或哺乳期暴露是否会影响后来的成年型Leydig细胞表型。在本研究中，Sprague-Dawley大鼠在短期妊娠/哺乳期窗口期间暴露于邻苯二甲酸二丁酯（DBP;从妊娠（GD）14.5天至出生后（PND）6天）或己烯雌酚（DES;从GD 14.5天至GD 16.5天），随后分析雄性后代的各种出生后睾丸参数。所有后代在整个研究期间保持良好的健康状况。母体异生物质处理似乎改变了雄性后代中特定的Leydig细胞基因表达，特别是在青春期中期的动态阶段，血清INSL 3浓度显示这些化合物导致更快达到峰值，并适度加速青春期轨迹。这种影响的一部分似乎是由于两种外源性物质对青春期间质细胞增殖的治疗特异性影响。总之，这些结果支持这样的观点，即母体暴露于某些外源性物质也可以影响成年型Leydig细胞群体的发育，可能是通过对Leydig干细胞群体的影响。
Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague-Dawley rats were exposed to dibutyl phthalate (DBP; from gestational day (GD) 14.5 to postnatal day (PND) 6) or diethylstilbestrol (DES; from GD14.5 to GD16.5) during a short gestational/lactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.