“…Rather, the driving mechanism underlying reproductive senescence in rodents is a significant dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis in middle age (for review, see Downs and Wise, 2009; Finch, 2014; Wise, 2002; Wise et al, 1989, 1996, 1997, 1999). Thus, the introduction of 4-vinylcyclohexene diepoxide (VCD) as a rodent model of transitional menopause has given researchers another tool to model menopause in the preclinical laboratory (for review, see Koebele and Bimonte-Nelson, 2016). VCD targets primordial and primary ovarian follicles by initiating accelerated atresia, or programmed cell death, in the ovary (Hoyer et al, 2001; Springer et al, 1996c), resulting in follicular depletion and eventual ovarian failure in rodents (Borman et al, 1999; Flaws et al, 1994; Hirshfield, 1991; Hoyer et al, 2001; Hu et al, 2001a, 2001b; Kao et al, 1999; Mayer et al, 2002, 2004, 2005; Springer et al, 1996a, 1996b, 1996c).…”