Effects of Short-Term High Fat/ High Sugar Diet on Follicle - Stimulating Hormone Secretion and Ovarian Gene Expression

Obesity is associated with decreased reproductive fitness including changes in the hypothalamic-pituitary-gonadal axis. Exposure to high fat diet can impair reproductive function even in the absence of obesity. Here, we tested the effects of a short-term high fat/high sugar (HF/HS) diet on the secretion pattern of follicle-stimulating hormone (FSH) and changes in gene expression in mouse ovaries. We used Fshb null mice expressing either a wild-type human FSHB transgene by which FSH is released constitutively or those expressing a mutant human FSHB transgene by which FSH is re-routed and released from the regulated LH secretory pathway. Mice were maintained on a HF/HS diet or regular chow for 10 weeks and serial blood samples were collected from tail tips for FSH analyses. RNA-Seq analysis was used to determine changes in ovarian gene expression. After 10 weeks on HF/HS diet, the mice did not develop obesity and allowed us to study the effects on FSH secretion characteristics. While area under the curve for FSH was unchanged, the amplitude of FSH was altered in re-routed FSH expressing mice on a HF/HS diet. We identified distinct changes in ovarian gene expression depending on the diet (regular vs. HF/HS) and FSH secretion pattern (constitutive vs. re-routed). Overall, re-routed FSH expressing mice maintained better ovarian gene expression even when fed on HF/HS diet. Thus, our re-routed FSH expressing transgenic mice provide a trackable genetic model to study the long-term effects of HF/HS diet and other metabolic syndromes on FSH secretion characteristics and the consequences on ovarian function.