Progressive obesity alters ovarian folliculogenesis with impacts on pro-inflammatory and steroidogenic signaling in female mice.

Abstract

Diet-induced obesity induces immune cell infiltration and inflammation in peri-ovarian adipose tissue and mRNA expression of inflammatory markers in ovarian tissue. Whether these changes are associated with obesity-related ovarian dysfunction remains unknown. In the present study, qRT-PCR and Western blotting techniques were used to compare mRNA and protein abundance of ovarian immune cell and inflammation markers, along with NF-kappaB and steroidogenic pathway members in normal wild-type non-agouti (a/a; lean) and lethal yellow mice (KK.CG-A(y/)J; obese) at 6, 12, 18, or 24 wk of age. Our data revealed that, beginning at 12 wk of age, NF-kappaB inflammatory signaling members were elevated (P < 0.05) in obese females. Interestingly obesity had opposing and temporal effects on the steroidogenic enzyme pathway. Obesity decreased (P < 0.05) STAR protein at 12, 18, and 24 wk of age. CYP11A1 and CYP19A1 proteins were increased (P < 0.05) at 12 wk but were decreased (P < 0.05) at 18 and 24 wk. Interestingly, CYP19A1 was increased in lethal yellow mouse ovaries at 6 wk of age, potentially indicating early puberty onset. These data demonstrate that obesity alters expression of ovarian inflammatory and steroidogenic pathway genes in ways which could adversely affect ovarian function.