Reproduction Abstracts

Introduction: Obesity and its associated metabolic disorders lead to ovarian failure and infertility. Nonetheless, the hierarchy of pathways leading to ovarian dysfunction is unknown. Presently, we studied the impact of obesity on ovarian innate immune response and steroidogenesis throughout the time.

Materials and methods: An in vivo study was conducted on C57Bl/6J mice (n=8/group) fed a chow-diet versus high-fat diet during 4- (C-4w; HFD-4w) or 16 weeks (C-16w; HFD-16w). Further on, whole ovaries were used for quantification of: i) Toll-like receptors (TLR)1, TLR2, TLR4, and TLR6 and downstream pathway proteins (MyD88, TRIF, Nfkβ2, and RELA); ii) tumor necrosis factor alpha (TNFα) and interleukin (IL)1β; and iii) steroidogenesis marker Star-protein mRNA transcription by Real-Time PCR.

Results and discussion: Consistently, both 4w and 16w HFD groups showed lower TLR1, TLR4, and TLR6 mRNA level (P<0.05). Regarding TLR2, mRNA was decreased only in HFD-4w, comparing with C-4w (P<0.01). Looking at TLR adaptors, MyD88 mRNA was decreased in HFD-4w and HFD-16w (P<0.05), while TRIF was diminished exclusively in HFD-16w (P<0.01). No changes were seen in Nfkβ2, whilst RELA presented lower mRNA in both HFD groups (P<0.05). Inflammatory markers IL1β and TNF were decreased in HFD-4w (P<0.05), but increased in HFD-16w (P<0.05), regarding respective controls. Star mRNA transcription was reduced in both HFD groups (P<0.01). Generally, the startling decrease in TLR and inflammatory markers mRNA after 4w may suggest HFD depresses local innate immunity, with a direct down-regulation of steroidogenesis. Further studies are being pursued to clarify TLRs role on ovarian failure due to obesity.