Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Biol Reprod. 2020 Oct 29;103(5):966-977. doi: 10.1093/biolre/ioaa146.
Development and functions of the ovary rely on appropriate signaling and communication between various ovarian cell types. FOXL2, a transcription factor that plays a key role at different stages of ovarian development, is associated with primary ovarian insufficiency and ovarian cancer as a result of its loss-of-function or mutations. In this study, we investigated the impact of aberrant, constitutive expression of FOXL2 in somatic cells of the ovary. Overexpression of FOXL2 that started during fetal life resulted in defects in nest breakdown and consequent formation of polyovular follicles. Granulosa cell differentiation was impaired and recruitment and differentiation of steroidogenic theca cells was compromised. As a consequence, adult ovaries overexpressing FOXL2 exhibited defects in compartmentalization of granulosa and theca cells, significant decreased steroidogenesis and lack of ovulation. These findings demonstrate that fine-tuned expression of FOXL2 is required for proper folliculogenesis and fertility.
卵巢的发育和功能依赖于各种卵巢细胞类型之间的适当信号传递和通讯。FOXL2 是一种转录因子，在卵巢发育的不同阶段发挥关键作用，其功能丧失或突变与原发性卵巢功能不全和卵巢癌有关。在这项研究中，我们研究了卵巢体细胞中 FOXL2 异常、组成性表达的影响。FOXL2 的过表达始于胎儿期，导致巢破裂缺陷，并导致多卵泡形成。颗粒细胞分化受损，甾体生成性间质细胞的募集和分化受到损害。因此，过表达 FOXL2 的成年卵巢表现出颗粒细胞和间质细胞分隔缺陷、类固醇生成显著减少和无排卵。这些发现表明，FOXL2 的精细表达对于正常的卵泡发生和生育能力是必需的。
