Relationship between androgen action in the "Male Programming Window," fetal sertoli cell number, and adult testis size in the rat
Relationship between androgen action in the "Male Programming Window," fetal sertoli cell number, and adult testis size in the rat
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DOI：
10.1210/en.2008-0413
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发表时间：
2008-10-01
期刊：
影响因子：
4.8
通讯作者：
Sharpe, Richard M.
中科院分区：
文献类型：
--
作者：
Scott, Hayley M.;Hutchison, Gary R.;Sharpe, Richard M.
胎儿雄激素作用是出生时支持细胞（SC）数量的重要决定因素。雄激素在胚胎 d(e) 15.5 和 e17.5（“雄性编程窗口”）之间“编程”大鼠的生殖道发育，这通过肛门生殖器距离 (AGD) 反映了终生。我们研究了雄激素对 SC 数量/增殖的调节是否也由该窗口中的雄激素编程。怀孕大鼠在不同的胎儿时间窗口用媒介物（对照）或 500 mg/kg .d 邻苯二甲酸二（正丁酯）（DBP）进行治疗，DBP 可抑制胎儿睾丸内睾酮（ITT）。 ITT和SC数/增殖指数在e17.5或e21.5测定； AGD 也在 e21.5 处确定。在对照中，从 e17.5-e21.5 来看，SC 数量增加了 11 倍，ITT 增加了 10 倍。在从 e13.5 开始每天暴露于 DBP 的动物中，SC 数量在 e21.5 时减少了约 50%，但从 e17.5-e21.5 期间增加了 6 倍，ITT 也是如此； DBP 在 e15.5 时对 ITT 没有影响，在 e17.5 时使 ITT 降低 50%，在 e19.5-21.5 时降低 75% 以上。仅在男性编程窗口中暴露 DBP 不会改变 e17.5 或 21.5 的 SC 数，但会降低 AGD。超过 e19.5 的 DBP 治疗导致 SC 数量/增殖指数和 ITT 在 e21.5 大幅减少。只有包含男性编程窗口的 DBP 治疗才会导致 e21.5 处的 AGD 降低，但 SC 数显然没有在此窗口中编程。然而，在子宫内暴露于媒介物或 DBP (e13.5-e21.5) 的动物中，睾丸重量与 e21.5 时的 AGD 以及出生后 25 和 90 d 高度相关 (P < 0.001)。因此，AGD 可以预测成人睾丸大小，但可能无法通过与 SC 数量的直接关系来预测。
Fetal androgen action is an important determinant of Sertoli cell (SC) number at birth. Androgens "program" reproductive tract development in rats between embryonic d(e) 15.5 and e17.5 ("male programming window"), and this is reflected for life by anogenital distance (AGD). We investigated if androgen regulation of SC number/proliferation was also programmed by androgens in this window. Pregnant rats were treated in various fetal time windows with vehicle ( control) or 500 mg/kg .d di(n-butyl) phthalate (DBP), which suppresses fetal intratesticular testosterone (ITT). ITT and SC number/proliferation index were determined at e17.5 or e21.5; AGD was also determined at e21.5. In controls, SC number increased 11-fold and ITT by 10-fold from e17.5-e21.5. In animals exposed daily to DBP from e13.5, SC number was reduced by approximately 50% at e21.5, but increased 6-fold, as did ITT, from e17.5-e21.5; DBP had no effect on ITT at e15.5, reduced ITT by 50% at e17.5, and by more than 75% at e19.5-21.5. DBP exposure just in the male programming window did not alter SC number at e17.5 or 21.5 but reduced AGD. DBP treatment beyond e19.5 caused major reductions in SC number/proliferation index and ITT at e21.5. Only DBP treatments that included the male programming window led to reduced AGD at e21.5, but SC number was clearly not programmed in this window. Nevertheless, testis weight correlated highly (P < 0.001) with AGD at e21.5, and postnatal d 25 and 90 in animals exposed in utero to vehicle or DBP(e13.5-e21.5). Thus, AGD may predict adult testis size but probably not through a direct relationship with SC number.