Although obesity is a known risk factor for subfertility, it is not understood how different obesogenic diets affect ovarian cells. We have previously shown that high fat diet (HFD) induces endoplasmic (ER) stress gene expression in both ovulated COCs and granulosa-lutein cells of female mice. However, modern diets additionally contain large amounts of sugar, likely triggering distinct stress responses in ovarian cells, which would impact oocyte quality at ovulation. Thus, we sought to investigate the effect of two distinct obesogenic Western-style diets on cellular stress responses in the preovulatory follicle.
6-week old female C57BL6J mice were randomly assigned to either HFD containing 60% energy from fat, a high-sugar high-fat diet (HSHFD) with an additional 13% w/v of high-fructose corn syrup, or control diet (CD) with 10% energy from fat. HSHFD females gained significantly more weight than the other groups. Both HFD/HSHFD groups showed dysregulated glucose tolerance at 12 weeks and 28 weeks; and insulin tolerance was also impaired after 28 weeks. At 40 weeks, animals were treated with PMSG to synchronize the preovulatory phase, and ovaries collected at 44h later. GCs and COCs were isolated from one ovary for gene expression analysis of Heat Shock (HSR) and ER stress response gene sets.
ER-stress genes Atf4 and Xbp1 were higher in HFD COCs. Expression of HSR genes Hspa1a, Hspa5, Hsp90aa1 and Hsp90b1 in GCs were significantly upregulated in GC by HFD, but curiously not in ovarian cells from the more obese HSHFD females. Similarly, expression of Hsf1, Hsp90aa1 and Hsp90ab1 were significantly upregulated in the COCs of HFD mice only.
Thus dietary fat and dietary sugar appear to elicit distinct stress responses in ovarian cells independent of obesity.