STUDY QUESTION Does anti-Müllerian hormone (AMH) induce preantral follicle atresia in mice? SUMMARY ANSWER The present findings suggest that AMH-mediated follicle atresia only occurs in early follicles before they become sensitive to FSH. WHAT IS KNOWN ALREADY Most prior studies have investigated the ability of AMH to inhibit primordial follicle activation. Our previous study showed that AMH-overexpressing mice had fewer preantral follicles than expected after accounting for primordial follicle inhibition but the reason for this was not determined. STUDY DESIGN, SIZE, DURATION Cross-sectional-control versus transgenic/knockout mouse studies were carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS Studies were conducted on female wild-type (Amh+/+), AMH-knockout (Amh-/-) and AMH overexpressing (Thy1.2-AMHTg/0) mice on a C57Bl/6J background (age: 42-120 days). The follicle counts were conducted for primordial, transitioning, primary, secondary and antral follicles in Amh-/- and Amh+/+ mice. After confirming that follicle development speeds were identical (proliferating cell nuclear antigen immunohistochemistry), the ratio of follicles surviving beyond each stage of folliculogenesis was determined in both genotypes. Evidence for increased rates of preantral follicle atresia was assessed by active caspase-3 immunohistochemistry in wild-type and Thy1.2-AMHTg/0 mice. MAIN RESULTS AND THE ROLE OF CHANCE Amh -/- mice at 100-120 days of age had lower primordial follicle counts but higher primordial follicle activation rates compared to Amh+/+ mice. These counteracting effects led to equivalent numbers of primordial follicles transitioning to the primary stage in Amh+/+ and Amh-/- mice. Despite this, Amh+/+ mice had fewer primary, secondary, small antral and medium antral follicles than Amh-/- mice indicating differing rates of developing follicle atresia between genotypes. Cleaved caspase-3 immunohistochemistry in Thy1.2-AMHTg/0 ovaries revealed high rates of granulosa cell and oocyte apoptosis in late primary/early secondary follicles of Thy1.2-AMHTg/0 mice. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The findings were shown only in one species and additional research will be required to determine generalizability to other species. WIDER IMPLICATIONS OF THE FINDINGS This study is consistent with prior studies showing that Amh-/- mice have increased primordial follicle activation but these new findings demonstrate that AMH-mediated preantral follicle atresia is a predominant cause of the increased small antral follicle counts in Amh-/- mice. This suggests that the role of AMH is not to conserve the ovarian reserve to prolong fertility, but instead to prevent the antral follicle pool from becoming too large. While this study may demonstrate a new function for AMH, the biological purpose of this function requires further investigation, particularly in mono-ovulatory species. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Health Research Council of New Zealand and the University of Otago. No competing interests to declare.

中文翻译：

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抗苗勒管激素介导的腔前卵泡闭锁是小鼠窦卵泡计数的关键决定因素。

研究问题 抗苗勒管激素 (AMH) 是否会诱发小鼠腔前卵泡闭锁？总结性回答 目前的研究结果表明，AMH 介导的卵泡闭锁仅发生在对 FSH 变得敏感之前的早期卵泡中。已知信息 大多数先前的研究都调查了 AMH 抑制原始卵泡激活的能力。我们之前的研究表明，在考虑原始卵泡抑制后，AMH 过表达小鼠的腔前卵泡比预期的要少，但其原因尚未确定。研究设计、规模、持续时间 进行了横断面对照与转基因/基因敲除小鼠研究。参与者/材料、环境、方法 对女性野生型 (Amh+/+)、AMH 敲除型 (Amh-/-) 和 AMH 过表达型 (Thy1. 2-AMHTg/0) C57Bl/6J 背景小鼠（年龄：42-120 天）。对 Amh-/- 和 Amh+/+ 小鼠的原始卵泡、过渡卵泡、初级卵泡、次级卵泡和窦卵泡进行了卵泡计数。在确认卵泡发育速度相同（增殖细胞核抗原免疫组织化学）后，确定了两种基因型中卵泡发生每个阶段后存活的卵泡比率。在野生型和 Thy1.2-AMHTg/0 小鼠中通过活性 caspase-3 免疫组织化学评估腔前卵泡闭锁率增加的证据。主要结果和机会的作用 与 Amh+/+ 小鼠相比，100-120 日龄的 Amh -/- 小鼠原始卵泡计数较低，但原始卵泡激活率较高。这些抵消作用导致在 Amh+/+ 和 Amh-/- 小鼠中等量的原始卵泡过渡到初级阶段。尽管如此，与 Amh-/- 小鼠相比，Amh+/+ 小鼠的初级、次级、小窦卵泡和中等窦卵泡较少，表明基因型之间卵泡闭锁的发生率不同。Thy1.2-AMHTg/0 卵巢中的裂解 caspase-3 免疫组织化学显示 Thy1.2-AMHTg/0 小鼠晚期初级/早期次级卵泡中颗粒细胞和卵母细胞凋亡率高。大规模数据 N/A。局限性、谨慎的原因 这些发现仅在一个物种中显示，需要进行更多研究以确定对其他物种的普遍性。研究结果的更广泛意义 这项研究与之前的研究一致，表明 Amh-/- 小鼠原始卵泡激活增加，但这些新发现表明 AMH 介导的腔前卵泡闭锁是 Amh-/- 小鼠小窦卵泡计数增加的主要原因/- 老鼠。这表明 AMH 的作用不是保护卵巢储备以延长生育能力，而是防止窦卵泡池变得过大。虽然这项研究可能证明了 AMH 的新功能，但该功能的生物学目的需要进一步研究，特别是在单排卵物种中。研究资金/竞争利益 本研究由新西兰卫生研究委员会和奥塔哥大学资助。没有要申报的竞争利益。