Endocrine Abstracts

In female mammals, the timing of the preovulatory LH surge depends on the combination of the positive estrogen feedback and a circadian signal which synchronizes the LH surge with the transition between the resting and active period at the end of the follicular phase, when arousal is maximal. Previous results have demonstrated that a functional biological clock, located in the suprachiasmatic nucleus (SCN), is required for optimal female fertility. In this context, we have investigated the consequences a chronodisruptive environment could have on the female mammals’ gonadotropic axis using a female mouse model of shiftwork. This is a relevant issue since an increasing number of women are working in non-standard work schedules in our modern 24 h/7 d society, and shift work is associated with reproductive deficits. Adult female mice were either kept in regular light/dark schedules or exposed to a model of shift work conditions (3 weeks rotation a 10-hour phase advance for three days and a 10-hour phase delay for four days). Daily rhythms in SCN vasopressin-containing neurons, kisspeptin neurons, LH secretion on the day of proestrus, as well as fertility parameters, were compared between both groups of mice. The chronodisruptive protocol reduces the number of the vasopressin neurons known to transmit the daily information to the kisspeptin neurons, abolished activation of kisspeptin neurons typically observed at the light/dark transition, and reduced the amplitude and altered the timing of the preovulatory LH surge. Furthermore, when female mice exposed to chronic shift are mated with a male, the number of gestation is reduced as compared to those observed in control female mice. Our results indicate that chronic shift desynchronizes the hypothalamic-pituitary-ovarian axis. Notably, chronic exposure to disrupted light/dark cycles impairs the vasopressin-induced daily activation of kisspeptin neurons which can explain the altered LH secretion and the reduced fertility in female mice. In future experiments, we will investigate whether peripheral clocks within the gonadotropic axis are also altered by chronic shift. Altogether, these experiments will provide a better understanding of circadian disruption’s potential on the daily reproductive rhythms of female mammals.