Abstract
Background
Skipping breakfast is associated with dysmenorrhea in young women. This suggests that the delay of food intake in the active phase impairs uterine functions by interfering with circadian rhythms.
Objective
To examine the relationship between the delay of feeding and uterine circadian rhythms, we investigated the effects of the first meal occasion in the active phase on the uterine clock.
Methods
Zeitgeber time (ZT) was defined as ZT 0 (8:45) with lights on and ZT 12 (20:45) with lights off. Young female mice (8 weeks of age) were divided into 3 groups: group I (ad-libitum feeding), group II (time-restricted feeding during ZT12–16, initial 4 hours of the active period), and group III (time-restricted feeding during ZT20–24, last 4 hours of the active period, a breakfast-skipping model). After two weeks of dietary restriction, mice in each group were sacrificed at 4-hour intervals and the expression profiles of uterine clock genes, Bmal1, Per1, Per2, and Cry1, were examined.
Results
qPCR and Western blot analyses demonstrated synchronized circadian clock gene expression within the uterus. Immunohistochemical analysis confirmed that Bmal1 protein expression was synchronized among the endometrium and myometrium. In groups I and II, mRNA expression of Bmal1 was elevated after ZT12 at the start of the active phase. In contrast, Bmal1 expression was elevated just after ZT20 in group III, showing that the uterine clock rhythm had shifted 8 hours backward. The changes in Bmal1 protein expression were confirmed by Western blot analysis.
Conclusion
This study is the first to indicate that time-restricted feeding regulates a circadian rhythm of the uterine clock that is synchronized throughout the uterine body. These findings suggest that the uterine clock system is a new candidate to explain the etiology of breakfast skipping-induced uterine dysfunction.
Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice
