title: 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.
authors.affiliation: Department of Animal Science, Iowa State University, Ames, Iowa.
authors.forename: Jackson
authors.initials: J
authors.lastname: Nteeba
authors.affiliation: Department of Animal Science, Iowa State University, Ames, Iowa.
authors.forename: Shanthi
authors.initials: S
authors.lastname: Ganesan
authors.affiliation: Department of Animal Science, Iowa State University, Ames, Iowa akeating@iastate.edu.
authors.forename: Aileen F
authors.initials: AF
authors.lastname: Keating
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D016207:Cytokines / Q000235:genetics; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D006080:Ovarian Follicle / Q000254:growth & development* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013256:Steroids / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D013256:Steroids
keywords: inflammation; obesity; ovary; steroidogenesis