Zhang Qin, Dong Zhen, Wu Xi, Yan Jie, Gao Ji-Min
Zhejiang Province Key Laboratory of Biotechnology and Application Mode, Wenzhou Medical University, Wenzhou 325035, China; MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China; Center for Systems Biology, Soochow University, Suzhou 215006, China. E-mail:
Sheng Li Xue Bao. 2013 Aug 25;65(4):395-401.
The circadian clock has been linked to female reproductive physiology and endocrine in mammals. Epidemiological studies of female shift workers have shown increased rates of abnormal reproduction and adverse pregnancy. But little is known how the circadian rhythms affect reproduction. The aim of the present study was to investigate the influences of circadian rhythms on estrous cycle in female mice using clock gene Rev-erb-α knock out (Rev-erb-α(-/-)) mice. To test the fertility of Rev-erb-α(-/-) mice, litter sizes were counted after mating with C57BL/6J male mice. HE staining was used to observe the change of follicle development. The number of embryos of Rev-erb-α(+/+) and Rev-erb-α(-/-) female mice was compared 1.5 d after mating with C57BL/6J male mice. Then Rev-erb-α(+/+) and Rev-erb-α(-/-) female mice were housed to adult, and daily vaginal lavage with 0.9% saline was used to monitor estrous cycle for at least 30 days. Quantity of various cells was counted on specified smears views after staining. We observed estrous cycles of Rev-erb-α(+/+) and Rev-erb-α(-/-) female mice using line plots and periodic spectrograms. The results showed that the Rev-erb-α(-/-) female mice were infertility, and the number of embryos of Rev-erb-α(-/-) females was less than that of Rev-erb-α(+/+) females. However, the follicle development of Rev-erb-α(-/-) female mice was normal. The estrous cycle of Rev-erb-α(-/-) female mice was 3.22 days longer than that of Rev-erb-α(+/+) female mice. The results suggest that loss of Rev-erb-α prolongs estrous cycle, which is probably one of the reasons for female mice infertility, and circadian rhythm is important for mammalian estrous cycle.
昼夜节律与哺乳动物的雌性生殖生理和内分泌有关。对女性轮班工作者的流行病学研究表明，异常生殖和不良妊娠的发生率有所增加。但昼夜节律如何影响生殖却知之甚少。本研究的目的是使用生物钟基因Rev-erb-α敲除（Rev-erb-α(-/-)）小鼠来研究昼夜节律对雌性小鼠发情周期的影响。为了测试Rev-erb-α(-/-)小鼠的生育能力，将其与C57BL/6J雄性小鼠交配后统计产仔数。采用苏木精-伊红（HE）染色观察卵泡发育的变化。将Rev-erb-α(+/+)和Rev-erb-α(-/-)雌性小鼠与C57BL/6J雄性小鼠交配1.5天后，比较两者的胚胎数量。然后将Rev-erb-α(+/+)和Rev-erb-α(-/-)雌性小鼠饲养至成年，每天用0.9%生理盐水进行阴道灌洗，以监测发情周期至少30天。染色后在特定涂片视野上计数各种细胞的数量。我们使用线图和周期谱图观察Rev-erb-α(+/+)和Rev-erb-α(-/-)雌性小鼠的发情周期。结果显示，Rev-erb-α(-/-)雌性小鼠不育，Rev-erb-α(-/-)雌性小鼠的胚胎数量少于Rev-erb-α(+/+)雌性小鼠。然而，Rev-erb-α(-/-)雌性小鼠的卵泡发育正常。Rev-erb-α(-/-)雌性小鼠的发情周期比Rev-erb-α(+/+)雌性小鼠长3.22天。结果表明，Rev-erb-α的缺失会延长发情周期，这可能是雌性小鼠不育的原因之一，并且昼夜节律对哺乳动物的发情周期很重要。
