Systemic changes in a mouse model of VCD-induced premature ovarian failure

Premature ovarian failure (POF) is a phenomenon in which the ovaries fail before the age of 40 years. Prior research has used a wide range of mouse models designed to reflect different causes of POF, including genetic factors, iatrogenic factors, and immune factors. The current study employed a mouse model of POF induced by 4-vinylcyclohexene diepoxide (VCD). VCD can specifically kill primordial and primary ovarian follicles, which destroys the follicular reserve and causes POF. The current study sought to specify and extend the applications of this model by examining the effect of timing and VCD dose and by exploring the effect of the model on systems outside of the ovaries. A VCD-induced mouse model of POF was constructed using established methods (VCD injected continuously at a concentration of 160 mg/kg for 15 days). Evidence for a graded effect of VCD was observed using a range of concentrations, and the best windows for examining VCD's effects on follicles and associated tissues were identified. The mouse model used here successfully simulated two common complications of POF – emotional changes and decreased bone density. The model's application was then extended to examine the links between disease and intestinal microorganisms, and evidence was found linking POF to the reproductively relevant composition of the gut microbiota. These findings provide novel methodological guidance for future research, and they significantly extend the applications and scope of VCD-induced POF mouse models.