Ovarian inflammation mediated by TLR-4 increased transcripts of maternal effect genes and decreased embryo development.

Obese women are sub-fertile and have reduced assisted reproduction success, which may be due to reduced oocyte competence. We hypothesize that consumption of a high fat high sugar (HFHS) diet induces ovarian inflammation, which is a primary contributor to decreased oocyte quality and pre-implantation embryo development. To test this hypothesis, C57BL/6 (B6) mice with a normal inflammatory response and C3H/HeJ (C3H) mice with a dampened inflammatory response due to dysfunctional toll-like receptor 4, were fed either normal chow (ND) or HFHS diet. In both B6 and C3H females, HFHS diet induced excessive adiposity and hyperglycemia compared to ND-fed counterparts. Conversely, ovarian CD68 levels and oocyte expression of oxidative stress markers were increased when collected from B6-HFHS but not C3H-HFHS mice. Following in vitro fertilization of in vivo matured oocytes, blastocyst development was decreased in B6-HFHS but not C3H-HFHS mice. Expression of cumulus cell markers of oocyte quality (Has2, Ptx3, Ptgs2, Tnfaip6) were altered in both B6-HFHS and C3H-HFHS. However, there were no diet-dependent differences in spindle abnormalities in either B6 or C3H mice, suggesting potential defects in cytoplasmic maturation. Indeed, there were significant increases in the abundance of maternal effect gene mRNAs in oocytes from only B6-HFHS mice. These differentially expressed genes encode proteins of the subcortical maternal complex and associated with mRNA metabolism and epigenetic modifications. These genes regulate maternal mRNA degradation at oocyte maturation, mRNA clearance at the zygotic genome activation, and methylation of imprinted genes suggesting a mechanism by which inflammation induced oxidative stress impairs embryo development.