Pregnancy Induces an Earlier Chronotype in Both Mice and Women

Abstract

Daily rhythms generated by endogenous circadian mechanisms and synchronized to the light-dark cycle have been implicated in the timing of birth in a wide variety of species. Although chronodisruption (e.g., shift work or clock gene mutations) is associated with poor reproductive outcomes, little is known about circadian timing during pregnancy. This study tested whether daily rhythms change during full-term pregnancies in mice and women. We compared running wheel activity continuously in both nonpregnant ( n = 14) and pregnant ( n = 13) 12- to 24-week-old C57BL/6NJ mice. We also monitored wrist actigraphy in women ( N = 39) for 2 weeks before conception and then throughout pregnancy and measured daily times of sleep onset. We found that on the third day of pregnancy, mice shift their activity to an earlier time compared with nonpregnant dams. Their time of daily activity onset was maximally advanced by almost 4 h around day 7 of pregnancy and then shifted back to the nonpregnant state approximately 1 week before delivery. Mice also showed reduced levels of locomotor activity during their last week of pregnancy. Similarly, in women, the timing of sleep onset was earlier during the first and second trimesters (gestational weeks 4-13 and 14-27) than before pregnancy and returned to the prepregnant state during the third trimester (weeks 28 until delivery). Women also showed reduced levels of locomotor activity throughout pregnancy. These results indicate that pregnancy induces changes in daily rhythms, altering both time of onset and amount of activity. These changes are conserved between mice and women.

Keywords: chronodisruption; chronotype; circadian rhythm; delivery; locomotor activity; pregnancy.

Figure 1.. Pregnancy shifts daily locomotor activity patterns in women and mice.

(A) Representative double-plotted actograms from two female mice recorded in a light-dark cycle as indicated by the white and black bars. (B-C) Representative single-plotted actograms of normal (Subject 1), early (Subject 2) and late (Subject 3) chronotype women for two weeks while non-pregnant (NP) and throughout their first, second and third trimesters (sunrise to sunset, yellow shading).

Figure 2.. The daily onset of activity in mice and sleep in women becomes earlier during early pregnancy.

(A) The daily activity onset advanced in mice in early pregnancy (open circles, mean ± SEM, n=13 mice) compared to the reliable daily activity onsets of non-pregnant dams (closed circles, n=14 mice) around dusk (light-dark cycle shown as white-black bar; repeated measures two-way ANOVA; P<0.05). (B) Sleep onset was significantly earlier in women (black circles, n=39) during their first trimester (T1) compared to before pregnancy or T2 or T3 (bars; Paired Wilcoxon Rank Sum test, * indicates P<0.05).

Figure 3.. Total activity diminishes across pregnancy in women and mice.

(A) Pregnant (P) mice (n=13, open circles) reduced their amount of daily wheel revolutions starting around day 12 of pregnancy compared to non-pregnant mice (n=14, NP, closed circles; mean ±SEM; Repeated measures two-way ANOVA; P<0.05). (B) Wrist activity decreased in women during pregnancy (counts x 10⁴; median, quartile 1 and 3, N=39) compared to pre-pregnancy (Paired Wilcoxon Rank Sum test; P<0.00001).