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首页> 外文期刊>Annals of the New York Academy of Sciences >Seminiferous Cord Formation and Germ-Cell Programming: Epigenetic Transgenerational Actions of Endocrine Disrupters
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Seminiferous Cord Formation and Germ-Cell Programming: Epigenetic Transgenerational Actions of Endocrine Disrupters

机译：生精索形成和生殖细胞编程：内分泌干扰物的表观遗传转化作用。

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The molecular and cellular control of embryonic testis development was investigated through an analysis of the embryonic testis transcrip-tome to identify potential regulatory factors for male sex determination and testis morphogenesis. One critical factor identified is neurotropin 3 (NT3). At the onset of male sex determination, Sertoli cells initiate differentiation and express NT3 to act as a chemotactic factor for mesonephros cells to migrate and associate with Sertoli-germ cell aggregates to promote cord formation. Promoter analysis suggests that NT3 may be an initial downstream gene to SRY and helps promote testis morphogenesis. Endocrine disruptors were used to potentially interfere with embryonic testis development and further investigate this biological process. The estrogenic pesticide methoxychlor and antiandrogenic fungicide vinclozolin were used. Previous studies have shown that methoxychlor and vinclozolin both interfere with embryonic testis cord formation and cause increased spermatogenic cell apoptosis in the adult testis. Interestingly, transient in vivo exposure to endocrine disruptors at the time of male sex determination caused a transgenerational phenotype (F1-F4) of spermatogenic cell apoptosis and subfertility. This apparent epigenetic mechanism involves altered DNA methylation and permanent re-programming of the male germ-line. A series of genes with altered DNA methylation and imprinting are being identified. Observations reviewed demonstrate that a transient embryonic in utero exposure to an endocrine disruptor influences the embryonic testis tran-scriptome and through epigenetic effects (e.g., DNA methylation) results in abnormal germ-cell differentiation that subsequently influences adult spermatogenic capacity and male fertility, and that this phenotype is transgenerational through the germ-line. The novel observations of transgenerational epigenetic endocrine disruptor actions on male reproduction critically impact the potential hazards of these compounds as environmental toxins. The literature reviewed provides insight into the molecular and cellular control of embryonic testis development, male sex determination, and the programming of the male germ-line.
机译：通过对胚胎睾丸转录图谱的分析来研究胚胎睾丸发育的分子和细胞控制，以确定男性性别决定和睾丸形态发生的潜在调控因素。鉴定出的一个关键因素是神经营养蛋白3（NT3）。在确定男性性别时，Sertoli细胞开始分化并表达NT3，作为中性粒细胞迁移和与Sertoli生殖细胞聚集体缔合以促进脐带形成的趋化因子。启动子分析表明NT3可能是SRY的初始下游基因，并有助于促进睾丸形态发生。内分泌干​​扰物被用来潜在地干扰胚胎睾丸的发育，并进一步研究这一生物学过程。使用了雌激素杀虫剂甲氧基氯和抗雄激素杀真菌剂长效唑啉。先前的研究表明，甲氧基氯和长春新唑啉均会干扰胚胎睾丸索的形成，并导致成年睾丸中生精细胞凋亡的增加。有趣的是，在确定男性时，体内短暂暴露于内分泌干扰物会导致生精细胞凋亡和亚生育力的跨代表型（F1-F4）。这种明显的表观遗传机制涉及改变的DNA甲基化和雄性种系的永久性重新编程。正在鉴定一系列具有改变的DNA甲基化和印迹的基因。审查的观察结果表明，子宫内短暂暴露于内分泌干扰物会影响胚胎睾丸的转录组，并通过表观遗传效应（例如DNA甲基化）导致生殖细胞分化异常，继而影响成年生精能力和男性生育能力，并且该表型是通过种系转世代的。跨代表观遗传内分泌干扰物对男性生殖的新发现严重影响了这些化合物作为环境毒素的潜在危害。综述的文献提供了对胚胎睾丸发育的分子和细胞控制，雄性决定以及雄性种系编程的见解。

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