Circadian Rhythms and Clock Genes in Reproduction: Insights From Behavior and the Female Rabbit's Brain

Abstract

Clock gene oscillations are necessary for a successful pregnancy and parturition, but little is known about their function during lactation, a period demanding from the mother multiple physiological and behavioral adaptations to fulfill the requirements of the offspring. First, we will focus on circadian rhythms and clock genes in reproductive tissues mainly in rodents. Disruption of circadian rhythms or proper rhythmic oscillations of clock genes provoke reproductive problems, as found in clock gene knockout mice. Then, we will focus mainly on the rabbit doe as this mammal nurses the young just once a day with circadian periodicity. This daily event synchronizes the behavior and the activity of specific brain regions critical for reproductive neuroendocrinology and maternal behavior, like the preoptic area. This region shows strong rhythms of the PER1 protein (product of the Per1 clock gene) associated with circadian nursing. Additionally, neuroendocrine cells related to milk production and ejections are also synchronized to daily nursing. A threshold of suckling is necessary to entrain once a day nursing; this process is independent of milk output as even virgin does (behaving maternally following anosmia) can display circadian nursing behavior. A timing motivational mechanism may regulate such behavior as mesolimbic dopaminergic cells are entrained by daily nursing. Finally, we will explore about the clinical importance of circadian rhythms. Indeed, women in chronic shift-work schedules show problems in their menstrual cycles and pregnancies and also have a high risk of preterm delivery, making this an important field of translational research.

Keywords: PER1 protein; lactation; maternal behavior; oxytocin; parturition; pregnancy; preoptic area; suckling.

Figure 1

Behavioral, physiological, and neural changes throughout circadian lactation in the rabbit doe. Abbreviations: A10vr, A10 ventral rostral; A10m, A10 medial; A10p, A10 posterior; FOS, c-Fos protein; mPFC, medial prefrontal cortex; NA, nucleus accumbens; OT, oxytocin; PHDA, periventricular hypophysial dopaminergic cells; POA, preoptic area; PVN, paraventricular nucleus of the hypothalamus; SON, supraoptic nucleus; TIDA, tuberoinfundibular dopaminergic cells; VTA, ventral tegmental area. In non-pregnant, non-lactating females FOS protein rhythms reach a peak at different hours in different structures, but in lactating does all of these rhythms shift to the hour of nursing. Figure derived from data previously published in Ref. (, , –64, 66, 79, 80).