Desynchronization between Food Intake and Light Stimulations Induces Uterine Clock Quiescence in Female Mice

Abstract

Background: Dysmenorrhea is associated with breakfast skipping in young women, suggesting that fasting in the early active phase disrupts uterine functions.

Objectives: To investigate the possible involvement of the uterine clock system in fasting-induced uterine dysfunction, we examined core clock gene expressions in the uterus using a 28-h interval-fed mouse model.

Methods: Young female mice (8 wk of age) were divided into 3 groups: group I (ad libitum feeding), group II (time-restricted feeding, initial 4 h of the active period every day), and group III (time-restricted feeding for 8 h with a 28-h cycle). Groups II and III have the same fasting interval of 20 h. After analyzing feeding and wheel running behaviors during 2 wk of dietary restriction, mice were sacrificed at 4-h intervals, and the expression profiles of clock genes in the uterus and liver were examined by qPCR.

Results: The mice in group I took food mainly during the dark phase and those in group II during the initial 4 h of the dark phase, whereas those in group III delayed feeding time by 4 h per cycle. In all groups, spontaneous wheel running was observed during the dark phase. There was no difference in the quantity of feeding and the amount of running exercise among the 3 groups during the second week. The mRNA expressions of peripheral clock genes, Bmal1, Clock, Per1, Per2, Cry1, Nr1d1, and Dbp and a clock-controlled gene, Fabp1, in the uterus showed rhythmic oscillations with normal sequential expression cascade in groups I and II, whereas their expressions decreased and circadian cycles disappeared in group III. In contrast, liver core clock genes in group III showed clear circadian cycles.

Conclusions: Fluctuations in the timing of the first food intake impair the uterine clock oscillator system to reduce clock gene expressions and abolish their circadian rhythms.

Keywords: circadian rhythms; clock gene; dysmenorrhea; meal timing; uterine function.