Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
Front Immunol. 2021 Feb 19;12:641164. doi: 10.3389/fimmu.2021.641164. eCollection 2021.
The increasing number of patients with infertility is recognized as an emerging problem worldwide. However, little is known about the cause of infertility. At present, it is believed that infertility may be related to genetic or abnormal immune responses. It has long been indicated that autoimmune regulator (AIRE), a transcription factor, participates in immune tolerance by regulating the expression of thousands of promiscuous tissue-specific antigens in medullary thymic epithelial cells (mTECs), which play a pivotal role in preventing autoimmune diseases. AIRE is also expressed in germ cell progenitors. Importantly, the deletion of AIRE leads to severe oophoritis and age-dependent depletion of follicular reserves and causes altered embryonic development in female mice. AIRE-deficient male mice exhibit altered apoptosis during spermatogenesis and have a significantly decreased breeding capacity. These reports suggest that AIRE deficiency may be responsible for infertility. The causes may be related to the production of autoantibodies against sperm, poor development of germ cells, and abnormal ovarian function, which eventually lead to infertility. Here, we focus on the potential associations of AIRE deficiency with infertility as well as the possible pathogenesis, providing insight into the significance of AIRE in the development of infertility.
越来越多的不孕患者被认为是一个全球性的新问题。然而，对于不孕的原因知之甚少。目前，人们认为不孕可能与遗传或异常的免疫反应有关。长期以来，人们一直认为自身免疫调节因子（AIRE）作为一种转录因子，通过调节骨髓胸腺上皮细胞（mTEC）中数千种混杂组织特异性抗原的表达，参与免疫耐受，mTEC 在防止自身免疫性疾病方面起着至关重要的作用。AIRE 也在生殖细胞祖细胞中表达。重要的是，AIRE 的缺失会导致严重的卵巢炎和卵泡储备随年龄的消耗，并导致雌性小鼠胚胎发育异常。AIRE 缺陷型雄性小鼠在精子发生过程中出现凋亡改变，繁殖能力显著下降。这些报告表明，AIRE 缺陷可能是导致不孕的原因。原因可能与针对精子的自身抗体的产生、生殖细胞发育不良和卵巢功能异常有关，最终导致不孕。在这里，我们重点讨论 AIRE 缺乏与不孕的潜在关联以及可能的发病机制，为 AIRE 在不孕发展中的意义提供深入了解。
