Disruption of aryl hydrocarbon receptor (AhR) induces regression of the seminal vesicle in aged male mice

Disruption of aryl hydrocarbon receptor (AhR) induces regression of the seminal vesicle in aged male mice
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DOI:
10.1159/000117714
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发表时间:
2008-01-01
期刊:
影响因子:
2.3
通讯作者:
Morohashi, K. -i.
Morohashi, K. -i.
中科院分区:
医学4区
文献类型:
--
作者:
Baba, T.;Shima, Y.;Morohashi, K. -i.

文献摘要

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芳香烃受体(AhR)是一种配体激活的转录因子,介导多种二恶英毒性。尽管介导了不利的影响,AhR基因在动物物种中是保守的,这表明AhR具有重要的生理功能。事实上,最近的一项研究表明,AhR在女性生殖中具有内在功能,尽管它在男性生殖中的作用在很大程度上是未知的。在这项研究中,我们展示了在AhR(-/-)雄性小鼠中,精囊可能与凝固腺一起随着年龄的增长而退化。基因敲除的小鼠有异常的阴道插管,附睾中精子数量低,生育能力低。此外,AhR(-/-)男性的血清睾酮水平和睾丸间质细胞中类固醇生成3β羟类固醇脱氢酶(3βHSD)和类固醇生成急性调节蛋白(STAR)的表达均降低。综上所述,我们的结果表明,衰老小鼠的睾酮合成受损会导致精囊和凝固腺退化。这种组织的消失可能会导致异常的阴道堵塞形成,最终导致低生育率。结合以往证明AhR在雌性生殖中的功能的研究结果,AhR在动物生殖中具有重要的功能。
The aryl hydrocarbon receptor ( AhR) is a ligand- activated transcription factor that mediates diverse dioxin toxicities. Despite mediating the adverse effects, the AhR gene is conserved among animal species, suggesting important physiological functions for AhR. In fact, a recent study revealed that AhR has an intrinsic function in female reproduction, though its role in male reproduction is largely unknown. In this study, we show age- dependent regression of the seminal vesicles, probably together with the coagulating gland, in AhR (-/-) male mice. Knockout mice had abnormal vaginal plugs, low sperm counts in the epididymis, and low fertility. Moreover, serum testosterone concentrations and expression of steroidogenic 3 beta hydroxysteroiddehydrogenase ( 3 beta Hsd) and steroidogenic acute regulatory protein ( StAR) in testicular Leydig cells were decreased in AhR ( -/ -) males. Taken together, our results suggest that impaired testosterone synthesis in aged mice induces regression of seminal vesicles and the coagulating glands. Such tissue disappearance likely resulted in abnormal vaginal plug formation, and eventually in low fertility. Together with previous findings demonstrating AhR function in female reproduction, AhR has essential functions in animal reproduction in both sexes.