Chronic circadian disruption in female mice induces a long‐term alteration of the preovulatory <scp>LH</scp> surge

In female mammals, many aspects of the reproductive function require precise synchronization of neuroendocrine and behavioral events for optimal fertility. To this end, the circadian timing system entrained by light exposure, in addition to the cyclical variations of sex steroid hormones, sets the pace of the hypothalamic-pituitary-ovarian axis. This is best illustrated by the preovulatory LH surge triggered by a daily signal generated by the master circadian clock at the resting-active period transition combined with the positive feedback from estradiol produced by maturing ovarian follicles at the end of the follicular phase. This ensures that ovulation occurs when sexual arousal is maximal, optimizing the chances for reproductive success. Although increasing evidence reports the direct impact of circadian disruption on female reproductive function in animals and humans, the potential long-term consequences remain unknown. Using a light-based shift work model in which adult female mice experienced a 10-h phase advance and a 10-h phase delay each week for 4 weeks (rotating shift condition), we investigated the long-term effects of such circadian disruption by monitoring reproductive rhythms after light exposure was normalized. Our results report a significant alteration in the timing and amplitude of the LH surge on the day of proestrus for up to 3 weeks after pre-exposure to disrupted light-dark cycles, despite regular estrous cycles. This long-lasting dysregulation of LH secretion may be linked to a delayed resynchronization of the internal timing system after exposure to rotating shift condition since locomotor activity also takes approximately 2 weeks to recover a robust daily rhythm. Given the significance of temporal homeostasis to proper reproduction, these findings emphasize the importance of investigating the long-lasting negative impacts of shift work on women's reproductive health.