Lin28a is an RNA binding protein and increasing evidence has indicated its role in regulating female fertility. Lin28a has been reported to be involved in ovarian follicle activation. However, its role and mechanisms in regulating primordial follicle activation have not yet been explored. To test whether overexpression of Lin28a activates ovarian primordial follicles, studies were conducted in wild type (WT) and Lin28a Tg mice. Female Lin28a Tg mice at 4-month old exhibited significantly smaller litter size and fewer ovulated oocytes when compared with the WT mice. By 6-month of age, these parameters in Lin28a Tg mice were less than 20% of the WT mice. At postnatal day (PD) 14, the number of primordial follicles was significantly decreased but the number of primary follicles was significantly increased in the transgenic mice. The number of primordial follicles, secondary and antral follicles in these mice were drastically reduced at PD21. In the ovary of Lin28a Tg mice, there were activation of Wnt/β-catenin signaling and its downstream mTOR pathway. Interestingly, overexpression of Lin28a, which can also act as transcriptional activator, activated Wnt signaling through enhancing the transcription of Wnt co-receptor LRP5. In conclusion, overexpression of Lin28a induced a primary ovarian insufficiency phenotype in long term via facilitating Wnt/β-catenin signaling leading to activation of primordial follicles.

Lin28a 是一种 RNA 结合蛋白，越来越多的证据表明它在调节女性生育能力中的作用。据报道，Lin28a 参与了卵泡的激活。然而，尚未探索其在调节原始卵泡激活中的作用和机制。为了测试Lin28a的过表达是否激活卵巢原始卵泡，在野生型 (WT) 和Lin28a Tg小鼠中进行了研究。与 WT 小鼠相比，4 个月大的雌性Lin28a Tg小鼠的产仔数明显更小，排卵的卵母细胞更少。到 6 个月大时，这些参数在Lin28a Tg小鼠不到 WT 小鼠的 20%。在出生后第 14 天，转基因小鼠的原始卵泡数量显着减少，但初级卵泡数量显着增加。这些小鼠的原始卵泡、次级卵泡和窦卵泡的数量在 PD21 时急剧减少。在Lin28a Tg小鼠的卵巢中，存在 Wnt/β-catenin 信号通路及其下游 mTOR 通路的激活。有趣的是，Lin28a的过表达，也可以作为转录激活因子，通过增强 Wnt 共受体 LRP5 的转录来激活 Wnt 信号传导。总之，Lin28a的过表达通过促进 Wnt/β-catenin 信号传导导致原始卵泡激活，长期诱导原发性卵巢功能不全表型。