Kobayashi Momoko, Watanabe Kaya, Matsumura Ritsuko, Anayama Nozomi, Miyamoto Akio, Miyazaki Hitoshi, Miyazaki Koyomi, Shimizu Takashi, Akashi Makoto
Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
The Research Institute for Time Studies, Yamaguchi University, Yamaguchi, Yamaguchi, Japan.
Genes Cells. 2018 Jun 19. doi: 10.1111/gtc.12605.
Circadian dysfunction perturbs the female reproductive cycle. In particular, mice lacking the clock gene Bmal1 show severe infertility, implying that BMAL1 plays roles in ovulation and luteinization. Here, we examined temporal changes in clock gene expression in the ovary and oviduct before and during gonadotropin-induced follicular growth, ovulation, and luteinization in sexually immature mice. While the oviduct did not show a drastic change in clock gene expression, Bmal1 expression in the ovary was higher than that in control mice during the period from 4 to 16 hr after human chorionic gonadotropin (hCG) administration. Bmal1 expression reached a maximum at 16 hr after hCG administration, when follicle luteinization occurred. In an interesting manner, administration of hCG to ex vivo-cultured oviduct triggered a shorter circadian period and inevitably resulted in phase advance. Together, our present data suggest that LH surge induces continuous expression of BMAL1 in the mouse ovary and modulates circadian phase in the mouse oviduct.
昼夜节律功能障碍会扰乱雌性生殖周期。具体而言,缺乏生物钟基因Bmal1的小鼠表现出严重的不育,这意味着BMAL1在排卵和黄体化过程中发挥作用。在此,我们研究了性未成熟小鼠在促性腺激素诱导卵泡生长、排卵和黄体化之前及期间,卵巢和输卵管中生物钟基因表达的时间变化。虽然输卵管中生物钟基因表达没有剧烈变化,但在人绒毛膜促性腺激素(hCG)给药后4至16小时期间,卵巢中Bmal1的表达高于对照小鼠。Bmal1表达在hCG给药后16小时达到最大值,此时卵泡发生黄体化。有趣的是,对体外培养的输卵管给予hCG会引发较短的昼夜节律周期,并不可避免地导致相位提前。总之,我们目前的数据表明,促黄体生成素激增会诱导小鼠卵巢中BMAL1的持续表达,并调节小鼠输卵管中的昼夜节律相位。