Cacciottola L, Camboni A, Dolmans M M
Gynecology Research Unit, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
Department of Anatomopathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Hum Reprod. 2025 Jan 1;40(1):12-22. doi: 10.1093/humrep/deae254.
The immune system plays a major role in ovarian physiology by regulating the ovarian follicle pool through complex signaling of different growth factors, cytokines, and chemokines. These may promote follicle activation and further growth but could also trigger follicle atresia and clearance of aging or damaged cells within the ovarian cortex. Moreover, extraglandular steroidogenesis potentially occurring in different immune cells like macrophages and natural killer cells might be another way of modulating follicle growth. Ovarian macrophages have recently been found to contain two different populations, namely resident macrophages and monocyte-derived cells, with potentially different roles. The immune system also plays a role in the development of pathological conditions, including premature ovarian insufficiency (POI). Indeed, autoimmune activation against various ovarian antigen targets results in lymphocytic oophoritis mainly targeting early growing follicles, but later leading to complete follicle pool depletion. Immune-mediated ovarian damage may also be caused by viral infection or be the consequence of iatrogenic damage. Certain novel cancer immunotherapies like checkpoint inhibitors have recently been shown to induce ovarian reserve damage in a murine model. Studies are needed to corroborate these findings and further investigate the potential of newly developed immunotherapies to treat POI. Technological advances such as single-cell analyses of less represented cell populations like immune cells inside the ovary are now contributing to valuable new information, which will hopefully lead to the development of new therapeutic strategies for women with fertility issues.
免疫系统在卵巢生理中发挥着重要作用，它通过不同生长因子、细胞因子和趋化因子的复杂信号传导来调节卵巢卵泡池。这些因子可能促进卵泡激活和进一步生长，但也可能引发卵泡闭锁以及清除卵巢皮质内衰老或受损的细胞。此外，在巨噬细胞和自然杀伤细胞等不同免疫细胞中可能发生的腺外类固醇生成，可能是调节卵泡生长的另一种方式。最近发现卵巢巨噬细胞包含两种不同的群体，即常驻巨噬细胞和单核细胞衍生细胞，它们可能具有不同的作用。免疫系统在包括卵巢早衰（POI）在内的病理状况发展中也起作用。事实上，针对各种卵巢抗原靶点的自身免疫激活会导致淋巴细胞性卵巢炎，主要针对早期生长的卵泡，但随后会导致卵泡池完全耗尽。免疫介导的卵巢损伤也可能由病毒感染引起，或者是医源性损伤的后果。最近在小鼠模型中发现，某些新型癌症免疫疗法如检查点抑制剂会导致卵巢储备损伤。需要开展研究来证实这些发现，并进一步研究新开发的免疫疗法治疗POI的潜力。诸如对卵巢内免疫细胞等代表性较少的细胞群体进行单细胞分析等技术进步，现在正在提供有价值的新信息，有望为有生育问题的女性开发新的治疗策略。
