Bisphenol A interferes with lncRNA Fhadlos2 and RUNX3 association in adolescent mouse ovary.

Bisphenol A (BPA) has a number of adverse effects on the reproductive development of females. In particular, the mechanism of disruption of ovarian development in adolescent mice is still unclear. Based on transcriptome sequencing results, a differentially expressed lncRNA, Fhad1os2 , was detected in the ovaries of BPA-exposed pubertal mice. In our study, the lncRNA Fhad1os2 , localized in the ovarian granulosa cell cytoplasm, could regulate the proliferation of mouse ovarian granulosa cells. Mechanistically, the results of RNA pull-down experiments as well as mass spectrometry analysis showed that ERα, an interfering signaling molecule of BPA, could directly bind lncRNA Fhad1os2 and decrease the transcription of lncRNA Fhad1os2 in response to the estrogen-like effect of BPA. BPA exposure also caused abnormal lncRNA Fhad1os2 pulldown protein-related signaling pathways in the ovaries of adolescent mice. Furthermore, lncRNA Fhad1os2 interacted with RUNX3, a transcription factor related to follicle development and hormone synthesis. As a negative regulator, lncRNA Fhad1os2 transactivated the expression of Runx3 , which in turn induced RUNX3 to positively regulate aromatase (Cyp19a1) expression in mouse ovarian granulosa cells and promote estrogen synthesis. In conclusion, our study indicates that BPA exposure interferes with ERα-regulated lncRNA Fhad1os2 interactions with RUNX3 in pubertal mice, affecting estrogen synthesis in mouse granulosa cells and contributing to premature ovarian maturation in pubertal mice. [Display omitted] • LncRNA Fhad1os2 regulates the proliferation of mouse ovarian granulosa cells. • ERα directly binds lncRNA Fhad1os2 and decreases the transcription of lncRNA Fhad1os2 in response to the estrogen-like effect of BPA. • BPA exposure interferes with ERα-regulated lncRNA Fhad1os2 interactions with RUNX3 in adolescent mouse. [ABSTRACT FROM AUTHOR]