Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary

Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary
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DOI:
10.1210/en.143.3.1076
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发表时间:
2002-03-01
期刊:
影响因子:
4.8
通讯作者:
Themmen, APN
Themmen, APN
中科院分区:
医学2区
文献类型:
--
作者:
Durlinger, ALL;Gruijters, MJG;Themmen, APN

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原始卵泡的募集对于女性生育力至关重要;然而,调节这一过程的确切机制在很大程度上是未知的。早期使用抗苗勒管激素(AMH)缺陷小鼠的研究表明,AMH参与调节原始卵泡募集。我们在新生儿卵巢培养系统中测试了这一假设,在该系统中,来自2天龄C57 Bl/6 J小鼠的卵巢在AMH存在或不存在的情况下培养2或4天。2日龄小鼠的卵巢含有多个原始卵泡,一些裸卵母细胞,在发育后期没有卵泡。我们观察到,在培养的卵巢中,无论是未经处理的还是AMH处理的,卵泡发育进展到与体内年龄相当的卵巢相同的程度,证实了我们的培养系统的有效性。然而,在AMH的存在下,与对照卵巢相比,培养的卵巢中生长的卵泡减少了40%。在培养4天后发现类似的减少。与这些发现一致,我们注意到AMH处理的卵巢中的BMPIN α-亚基表达低于未处理的卵巢。与此相反,AMH配体11型受体的表达和卵母细胞标志物生长和分化因子9和透明质酸蛋白3的表达不受AMH的影响。基于上述结果,我们认为AMH抑制原始卵泡生长的启动,因此在卵泡发育的早期阶段,AMH在卵巢中起抑制性生长因子的作用。
Recruitment of primordial follicles is essential for female fertility; however, the exact mechanisms regulating this process are largely unknown. Earlier studies using anti-Mullerian hormone (AMH)-deficient mice suggested that AMH is involved in the regulation of primordial follicle recruitment. We tested this hypothesis in a neonatal ovary culture system, in which ovaries from 2-d-old C57Bl/6J mice were cultured for 2 or 4 d in the absence or presence of AMH. Ovaries from 2-d-old mice contain multiple primordial follicles, some naked oocytes, and no follicles at later stages of development. We observed that in the cultured ovaries, either nontreated or AMH-treated, follicular development progressed to the same extent as in in vivo ovaries of comparable age, confirming the validity of our culture system. However, in the presence of AMH, cultured ovaries contained 40% fewer growing follicles compared with control ovaries. A similar reduction was found after 4 d of culture. Consistent with these findings, we noted lower inhibin a-subunit expression in AMH-treated ovaries compared with untreated ovaries. In contrast, expression of AMH ligand type 11 receptor and the expression of oocyte markers growth and differentiation factor 9 and zona pellucida protein 3 were not influenced by AMH.Based on the results, we suggest that AMH inhibits initiation of primordial follicle growth and therefore functions as an inhibitory growth factor in the ovary during these early stages of folliculogenesis.