ESR2 regulates indian hedgehog signaling in neonatal rat ovary

Abstract

The transcriptional regulatory function of estrogen receptor β (ESR2) is essential for the regulation of primordial follicle activation (PFA). Increased PFA due to the loss of ESR2 becomes evident as early as postnatal day 8 (PND8). To identify the ESR2-regulated genes that control PFA, we performed RNA-seq analyses of wildtype, and Esr2 knockout (Esr2KO) neonatal rat ovaries collected on PND4, PND6, and PND8. Among the differentially expressed genes in Esr2KO ovaries, indian hedgehog (Ihh) displayed the highest downregulation among the ovary enriched genes. IHH regulated genes including Hhip as well as the steroidogenic enzymes were also downregulated in Esr2KO rat ovaries. Remarkably, the expression of Ihh in Esr2KO ovaries was not upregulated despite the high levels of Gdf9 and Bmp15, which are known regulators of Ihh expression in granulosa cells. Our findings suggest that indian hedgehog signaling in the neonatal rat ovary is dependent on ESR2.