NRDR Affects Steroid Hormone Synthesis Of Granulosa Cells And Is Associated With Changes In Reproductive Traits In Pigs

Cumulus cells secreting steroid hormones have important functions in oocyte development.Several members of the short chain dehydrogenase/reductase(SDR)family are critical to the biosynthesis of steroid hormones.NADPH-dependent retinol dehydrogenase/reductase(NRDR),a member of the SDR superfamily,is over-expressed in pig breeds,which also show high levels of androstenone.However,the potential functions and regulatory mechanisms of NRDR in pig oocyte development have not been reported until now.In this study,we demonstrate that NRDR is highly expressed in pig ovary and specifically located in cumulus granulosa cells.Functional studies show that NRDR inhibition increased estradiol synthesis.Both pregnant mare serum gonadotropin(PMSG)and human chorionic gonadotropin(hCG)down-regulated the expression of NRDR in pig cumulus granulosa cells.When the relationship between reproductive traits and single-nucleotide polymorphisms(SNPs)of the NRDR gene was examined,we found that two SNPs affected reproductive traits.SNP rs701332503 was significantly associated with changes in the total number of piglets born during multiparity,and rs326982309 was significantly associated with changes in the average birth weight during primiparity.We conclude that NRDR has an important role in steroid hormone biosynthesis in cumulus granulosa cells and NRDR SNPs are associated with changes in porcine reproduction traits.