Estrus Synchronization and Ovarian Hyper Stimulation Treatments Have Negligible Effects on Cumulus Oocyte Complexes Gene Expression: Induction of Ovulation Causes Major Expression Changes

The effects of exogenous hormones used for estrus synchronization, and ovarian hyper stimulation on cumulus oocyte complexes (COCs) gene expression in sexually mature rats were determined using microarrays. Gene expression in COCs collected from GnRH (Gtrt), GnRH+eCG (G+Etrt), and GnRH+eCG+hCG (G+E+Htrt) treatments were compared to COCs from naturally cycling (NC) rats. There was no significant difference in gene expression among NC, Gtrt and G+Etrt. Over 2600 genes were significantly different between NC and G+E+Htrt (P<0.05). Genes encoding proteins that are involved in prostaglandin synthesis (Ptgs2, Pla2g4a, Runx1); cholesterol biosynthesis (Hmgcr, Sc4mol, Dhcr24); receptors that allow cholesterol uptake (Ldlr, Scarb1); regulate progesterone synthesis (Star); inactivate estrogen (Sult1e1); and downstream effectors of LH signal (Pgr, Cebpb, Creb3l1, Areg, Ereg, Adamts1) were upregulated in G+E+Htrt. Genes encoding proteins that are involved in DNA replication (Ccne2, Orc5l, Rad50, Mcm6); reproductive developmental process and granulosa cell expansion (Gdf9, Bmp15, Amh, Amhr2, Bmpr1b, Tgfb2, Foxl2, Pde3a, Esr2, Fshr, Ybx2, Ccnd2, Ccnb1ip1, Zp3); maternal effect genes that are important for embryo development (Zar1, Npm2, Nlrp5, Dnmt1, H1foo, Zfp57); amino acid degradation and ketogenesis (Hmgcs2 , Cpt1b) were downregulated in G+E+Htrt. These results on rat model show that hormones used for estrus synchronization (Gtrt) and ovarian hyper stimulation (G+Etrt) had minimal effects on gene expression. However, induction of ovulation (G+E+Htrt) caused major changes in gene expression of rat COCs. This study provides comprehensive information about regulated genes during late follicle development and ovulation induction. Four experimental groups were used and there were 6 animals in each group. Total of 24 arrays were used. Only raw data used in publication.