Androgen action in the masculinization programming window and development of male reproductive organs
Androgen action in the masculinization programming window and development of male reproductive organs
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DOI：
10.1111/j.1365-2605.2009.01005.x
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发表时间：
2010-04-01
影响因子：
--
通讯作者：
van den Driesche, S.
中科院分区：
文献类型：
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作者：
MacLeod, D. J.;Sharpe, R. M.;van den Driesche, S.
我们以前已经表明，在雄性化编程窗口（MPW;大鼠e15.5-e18.5）内缺乏雄激素作用在雄性生殖障碍的起源和雄性生殖器官大小的编程中是重要的，但出生后雄激素作用可能对实现这一大小很重要。为了进一步研究MPW的重要性，我们使用了两种大鼠模型，其中胎儿雄激素的产生或作用在MPW期间通过在子宫内暴露于邻苯二甲酸二（正丁基）酯（DBP）或氟哌酸而受损。减少肛门生殖器距离（AGD）被用作MPW期间雄激素产生/作用的监测器。在青春期早期（Pnd 25）评价后代，以确定生殖器官大小是否改变。称量睾丸、阴茎、腹侧前列腺（VP）和精囊（SV）的重量，并测量阴茎长度。MPW中的DBP和氟他胺暴露均显着降低了Pnd 25时的阴茎、VP和SV尺寸以及AGD; AGD和器官尺寸高度相关。沿着。在DBP暴露的动物中，睾丸重量也降低，并与AGD相关，但氟替卡松暴露的动物除外。在MPW期间（e17.5）或之后（e21.5），还在对照组和DBP暴露组雄性动物中测量了睾丸内睾酮，并与e21.5时的AGD相关。为了评价出生后雄激素作用在生殖器官生长中的重要性，评价了产前和出生后母体治疗的组合对Pnd 25时AGD和阴茎大小的影响。在出生前DBP暴露的动物，进一步出生后暴露于DBP或fluorescent显着降低AGD和阴茎大小相比，出生前DBP暴露单独。相比之下，大鼠出生后暴露于丙酸睾酮后，产前车辆暴露显示这些参数与对照组相当大的增加。总之，我们表明，所有男性生殖器官的大小是由雄激素暴露在MPW编程，但这个大小的增长是依赖于雄激素的作用出生后。
P>We have shown previously that deficient androgen action within a masculinization programming window (MPW; e15.5-e18.5 in rats) is important in the origin of male reproductive disorders and in programming male reproductive organ size, but that androgen action postnatally may be important to achieve this size. To further investigate importance of the MPW, we used two rat models, in which foetal androgen production or action was impaired during the MPW by exposing in utero to either di(n-butyl) phthalate (DBP) or to flutamide. Reduced anogenital distance (AGD) was used as a monitor of androgen production/action during the MPW. Offspring were evaluated in early puberty (Pnd25) to establish if reproductive organ size was altered. The testes, penis, ventral prostate (VP) and seminal vesicles (SV) were weighed and penis length measured. Both DBP and flutamide exposure in the MPW significantly reduced penis, VP and SV size along with AGD at Pnd25; AGD and organ size were highly correlated. In DBP-, but not flutamide-, exposed animals, testis weight was also reduced and correlated with AGD. Intratesticular testosterone was also measured in control and DBP-exposed males during (e17.5) or after (e21.5) the MPW and related to AGD at e21.5. To evaluate the importance of postnatal androgen action in reproductive organ growth, the effect of combinations of prenatal and postnatal maternal treatments on AGD and penis size at Pnd25 was evaluated. In prenatally DBP-exposed animals, further postnatal exposure to either DBP or flutamide significantly reduced AGD and penis size in comparison with prenatal DBP exposure alone. In comparison, rats exposed postnatally to testosterone propionate after prenatal vehicle-exposure showed considerable increase in these parameters vs. controls. In conclusion, we show that the size of all male reproductive organs is programmed by androgen exposure in the MPW, but that growth towards this size is dependent on androgen action postnatally.