Longitudinal studies of estrous cyclicity in C57BL/6J mice: III. Dietary modulation declines during aging

Dietary modulation of estrous cyclicity was studied throughout the reproductive lifespan to assess the stability of age-related changes in cyclicity and to probe underlying mechanisms. Animals were fed a standard diet or an isocaloric breeder diet that differed in nutrient composition to promote fecundity. In young mice, the breeder diet more than doubled the frequency of short (4-day) cycles, and, as a result, increased the total number of cycles during the cycling lifespan by 10%. Dietary potentiation of short cycles disappeared between 7 and 9 months of age, and most subsequent age-related changes in cyclicity were resistant to dietary influence. The breeder diet had no effect on the transition from 4- to 5-day cycles, the onset of acyclicity, or on the incidence or duration of persistent vaginal cornification. It only delayed the increase of very long (greater than 5-day) cycles by 1 month. These results show that most age-related changes in cyclicity are not influenced by dietary differences that affect cyclicity in young mice, and that diminished responsiveness to dietary variation is among the earliest age-related changes in the reproductive system. In addition, the results suggest that differences in cycle frequency and, presumably, in cumulative exposure to pre-ovulatory elevations of ovarian steroids do not influence the cycling lifespan in this strain of mouse.