C-type natriuretic peptide promotes human granulosa cell growth and estradiol production: Implications for early follicle development

PurposeTo investigate the effects of C-type natriuretic peptide (CNP) on human granulosa cell growth and elucidate its regulatory mechanisms.MethodsA human non-luteinizing granulosa cell line (HGrC) developed from small antral follicles was used to assess the impact of CNP on cell proliferation and estrogen synthesis. cGMP production via the guanylate cyclase domain of the CNP receptor, natriuretic peptide receptor 2 (NPR2), was confirmed. The regulation of CNP encoding natriuretic peptide C (NPPC) and NPR2 by estradiol and oocyte-derived factors (ODFs) was examined.ResultsBesides detecting both NPPC and NPR2, CNP increased cellular proliferation. The specific action of CNP on cell proliferation was confirmed using siRNA transfection. CNP stimulated cGMP production, whereas a guanylate-cyclase inhibitor suppressed CNP-induced cell proliferation. Estradiol production was elevated by CNP treatment, accompanied by increased expression of estrogen synthetic enzymes. Furthermore, CNP upregulated NPR2 expression in cooperation with estradiol and ODFs, while estradiol increased NPPC expression.ConclusionThis study demonstrates CNP stimulation of human granulosa cell growth and suggests potential cross-talk between these cells and oocytes. Further research on the simultaneous administration of CNP and estradiol may offer a promising approach for promoting early-stage follicle development in infertility treatments for patients with poor ovarian reserve.