Aberrant and constitutive expression of FOXL2 impairs ovarian development and functions in mice
Barbara Nicol1, Karina Rodriguez1, Humphrey H-C Yao1
1Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Abstract:
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.
Insights
Proper ovarian function requires precise control of the FOXL2 gene. Aberrant expression of FOXL2 disrupts ovarian development, leading to infertility and impaired folliculogenesis.
Area of Science:
- Reproductive biology
- Molecular endocrinology
- Developmental biology
Background:
- Ovarian development and function depend on intricate cell signaling.
- FOXL2, a crucial transcription factor, is implicated in ovarian insufficiency and cancer due to mutations.
- Understanding FOXL2's role in normal ovarian function is vital.
Purpose of the Study:
- To investigate the consequences of aberrant, constitutive FOXL2 expression in ovarian somatic cells.
- To elucidate the impact of altered FOXL2 levels on folliculogenesis and fertility.
Main Methods:
- Utilized a model of FOXL2 overexpression initiated during fetal development.
- Analyzed ovarian morphology, cell differentiation, steroidogenesis, and ovulation.
- Examined the effects on granulosa and theca cell development and function.
Main Results:
- Early FOXL2 overexpression caused defects in ovarian nest breakdown and polyovular follicle formation.
- Impaired granulosa cell differentiation and compromised theca cell recruitment and differentiation.
- Adult ovaries showed disrupted cell compartmentalization, reduced steroidogenesis, and an absence of ovulation.
Conclusions:
- Fine-tuned FOXL2 expression is essential for proper ovarian folliculogenesis.
- Aberrant FOXL2 signaling disrupts normal ovarian development and leads to infertility.
- This study highlights the critical role of precise gene regulation in reproductive health.
