Circadian rhythms in sexual behavior and their influence on reproductive outcomes in mice

Abstract

Circadian clocks coordinate mammalian reproductive physiology, and circadian misalignment (resulting from shift work, jet lag, etc.) is known to impair fertility. Despite the well-established links between clock function and reproductive success, it remains unclear whether male and female mice maintained under standard ad libitum feeding conditions exhibit circadian rhythms in the propensity for sexual behavior, and to what degree such timing influences reproductive outcomes. Using standardized mating paradigms in C57BL/6J mice, we identified a circadian rhythm in sexual behavior in both sexes, with peak sexual activity most often occurring at circadian time (CT) 13-16 and a trough at CT4-7. To test the functional significance of these rhythms, we conducted 1-hour mating trials across four cohorts of C57BL/6J mice with pairs of mice having either aligned (e.g. male CT16 peak and female CT16 peak) or misaligned (e.g. male CT16 peak and female CT4 nadir) sexual behavior phases and monitored mating outcomes via ultrasound. While pregnancies were almost as frequent across all four cohorts, the numbers of live offspring were significantly more frequent when both the male and female mated at their peak phases than when both mice mated at their troughs. Notably, mating specifically during the males behavioral peak increased the likelihood of successful delivery of pups, suggesting that male circadian phase is a key determinant of miscarriage vs successful birth. These findings establish a circadian rhythm in the propensity for sexual behavior under standard feeding and housing conditions and indicate that mating time--particularly relative to the males circadian peak--can influence reproductive success. This insight provides a foundation for translational studies that explore whether intercourse timed to the circadian rhythms of the couple might help to increase fertility chances.