The Masculinization Programming Window
The Masculinization Programming Window
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DOI：
10.1159/000363609
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发表时间：
2014-01-01
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影响因子：
--
通讯作者：
Yamada, Gen
中科院分区：
文献类型：
--
作者：
Welsh, Michelle;Suzuki, Hiroko;Yamada, Gen
性别分化是一系列严格控制的事件，这些事件将冷漠的性腺和生殖器转变为性别特有的结构。这是由胎儿睾丸产生的激素推动的，主要是睾酮(T)。然而，每个结构的男性化并不是同步发生的，直到最近，人们还推测，在胎儿生命的广泛时期，雄激素也控制着这种男性化，这与胎儿T产生的时期一致。然而，在雄性和雌性啮齿动物模型中，已经发现了一个共同的胎儿男性化编程窗口(MPW)，在该模型中，雄激素必须作用于雄性化生殖道的所有组成部分，并允许它们在以后的完整发育中。雄激素作用受损，仅在此MPW内可诱发隐睾症和尿道下裂。这种MPW很可能发生在人类怀孕8-14周之间。对转基因小鼠的研究已经开始探索其中的一些潜在机制。肛门发育距离可以预测无精子症、尿道下裂和隐睾症等疾病的发生率，并可在这一MPW中提供一个无创性的、终生的雄激素作用指标，对于性发育障碍患者的临床评估很有用。此外，外生殖器的几个诊断特征在研究这种MPW时也很有用。(C)2014年S.Karger AG，巴塞尔
Sexual differentiation is a tightly regulated series of events which transform the indifferent gonads and genitalia into sex-specific structures. This is driven by hormones produced by the fetal testes, primarily testosterone (T). However, masculinization of each structure does not occur synchronously and, until recently, it was presumed that androgens also control this masculinization over a broad period of fetal life, coincident with the period of fetal T production. However, a common fetal masculinization programming window (MPW) has been identified in male and female rodent models in which androgens must act to masculinize all components of the reproductive tract and allow their later complete development. Impaired androgen action only within this MPW can induce cryptorchidism and hypospadias. This MPW is likely to occur between 8-14 weeks' gestation in humans. Studies in transgenic mice have begun to investigate some of the underlying mechanisms involved. Anogenital distance is predictive of the incidence of disorders, such as azoospermia, hypospadias and cryptorchidism, and could provide a noninvasive, lifelong indicator of androgen action within this MPW, useful in clinical assessment of patients with disorders of sexual development. In addition, several diagnostic characteristics of the external genitalia are also useful in investigating this MPW. (C) 2014 S. Karger AG, Basel