Med1 regulates meiotic progression during spermatogenesis in mice.
Med1 regulates meiotic progression during spermatogenesis in mice.
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DOI：
10.1530/rep-14-0483
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发表时间：
2015-06
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影响因子：
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通讯作者：
Payne CJ
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文献类型：
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作者：
Huszar JM;Jia Y;Reddy JK;Payne CJ
精子发生是一个高度协调的过程。来自核激素受体的信号，如维甲酸的信号，对正常的精子发生很重要。然而，调控这些信号的机制却知之甚少。介质复合体亚基1 （MED1）是一种转录增强子，直接调节核激素受体的转录。MED1在哺乳动物发育过程中存在于雄性生殖细胞中，但其在精子发生过程中的功能尚不清楚。为了确定它的作用，我们在出生前制造了生殖细胞中特异性缺乏Med1的小鼠。条件Med1基因敲除的雄性具有生育能力，睾丸重量正常，后代数量正常。视黄酸基因8 （STRA8）和突触复合蛋白3 （SYCP3）刺激的视黄酸应答基因产物在精子发生第一波的预期时间点首次在敲除精原细胞中检测到，并在成年敲除睾丸中保持正常的细胞分布模式。然而，减数分裂过程在Med1缺失的情况下发生改变。在出生后第7天（P7），已检测到合子蛋白期敲除精母细胞，与对照睾丸不同，敲除中观察到的瘦素前期细胞较少，而瘦素期精母细胞较多。在P9时，Med1敲除的精母细胞过早进入厚膜瘤。在成年睾丸发育和维持过程中，相对于减数分裂的其他阶段，大量的敲除精母细胞在厚膜瘤中形成。减数分裂退出不受抑制。我们得出结论，MED1通过减数分裂调节原代精母细胞的时间进程，其缺失导致瘦素前期、瘦素期和zygotene期缩短，粗素期延长。
Spermatogenesis is a highly coordinated process. Signaling from nuclear hormone receptors, like those for retinoic acid, is important for normal spermatogenesis. However, the mechanisms regulating these signals are poorly understood. Mediator complex subunit 1 (MED1) is a transcriptional enhancer that directly modulates transcription from nuclear hormone receptors. MED1 is present in male germ cells throughout mammalian development, but its function during spermatogenesis is unknown. To determine its role, we generated mice lacking Med1 specifically in their germ cells beginning just before birth. Conditional Med1 knockout males are fertile, exhibiting normal testis weights and siring ordinary numbers of offspring. Retinoic acid-responsive gene products Stimulated by retinoic acid gene 8 (STRA8) and Synaptonemal complex protein 3 (SYCP3) are first detected in knockout spermatogonia at the expected time points during the first wave of spermatogenesis and persist with normal patterns of cellular distribution in adult knockout testes. Meiotic progression, however, is altered in the absence of Med1. At postnatal day 7 (P7), zygotene-stage knockout spermatocytes are already detected, unlike in control testes, with fewer pre-leptotene-stage cells and more leptotene spermatocytes observed in the knockouts. At P9, Med1 knockout spermatocytes prematurely enter pachynema. Once formed, greater numbers of knockout spermatocytes remain in pachynema relative to the other stages of meiosis throughout testis development and its maintenance in the adult. Meiotic exit is not inhibited. We conclude that MED1 regulates the temporal progression of primary spermatocytes through meiosis, with its absence resulting in abbreviated pre-leptotene, leptotene and zygotene stages, and a prolonged pachytene stage.