Seasonality of the estrus cycle in laboratory mice under constant conditions.

Seasonality governs every aspect of life in the natural environment. Controlled laboratory settings are intended to keep animals under a constant set of environmental cues with no seasonality. However, prior research suggests that seasonal variation may exist despite aseasonal lab environments. Here, we examined whether the length of each phase of the estrus cycle varied seasonally in addition to seasonal changes in the overall estrus cycle length in a laboratory mouse strain (C57BL/6J) under standard laboratory housing conditions. We found that female C57BL/6J mice exhibited reproductive seasonality mirroring the outside environment, in a controlled "simulated summer" environment. In the winter and spring, females have longer ovulating phases (proestrus and estrus), compared to the fall. Females similarly experience lengthier quiescent phases (metestrus and diestrus) in the summer, compared to fall and winter. Interestingly, females showed no significant variation in overall estrus cycle length across seasons. Notably, females spent more time in ovulating phases across seasons than previously reported. Laboratory mice are sensitive to external seasonal changes, even when housed in standard laboratory environments designed to control light, temperature, and humidity. Humidity is indicated by some analyses as a potential seasonal cue, however, we cannot rule out other unidentified external cues that may provide information about external seasonal changes. These findings represent just one example of how seasonality may impact mouse physiology in laboratory settings, emphasizing the need to account for such influences in biomedical research and improve environmental control in mouse holding facilities.