睡眠剥夺致雌性大鼠生育力下降及其机制

Sleep deprivation induced fertility decline in female rats and its mechanism

睡眠是人体维持时辰节律稳态的关键生理过程,主客观原因导致的睡眠剥夺(SD,sleep deprivation)十分常见。SD与生育相关研究正日益引起重视。本研究采用改良多平台睡眠剥夺法(MMPM)建立雌性Wistar大鼠的睡眠剥夺模型,考察大鼠一般情况、卵巢病理、动情周期、交配率和妊娠率,判断SD对雌性大鼠生育力的影响情况;应用新一代测序(NGS)技术,通过RNA测序(RNA-Seq,RNA sequencing)和DNA甲基化测序,研究SD雌性大鼠卵巢转录组及表观遗传的差异。研究结果表明SD导致雌性大鼠动情周期异常、妊娠率下降、卵巢病理结构改变;SD大鼠卵巢组织发现了101个显著差异表达基因(52个上调基因和49个下调基因),SD50组与对照组之间发现26个甲基化显著差异区域,但上述101个差异基因的所有位点,均未检测到甲基化水平变化。SD雌性大鼠的生育指标差异表明SD导致雌性Wistar大鼠生育力下降;SD大鼠卵巢的差异表达基因及甲基化差异显示SD可能通过基因转录、表观遗传调控来影响雌性动物性腺功能。

Sleep is a key physiological process to maintain the homeostasis of the human circadian rhythm,and sleep deprivation(SD)caused by subjective and objective reasons is very common.The research on the relationship between SD and fertility is attracting more and more attention.In this study,the modified multiple platform method(MMPM)was used to establish the sleep deprivation model of female Wistar rats.The general conditions,ovarian pathology,oestrus cycle,mating rate and pregnancy rate of the rats were investigated to determine the effect of SD on the fertility of female rats;The new generation sequencing(NGS)technology was used to study the differences of ovarian transcriptome and epigenetic in SD female rats by RNA sequencing(RNA-Seq)and DNA methylation sequencing.The results showed that SD led to abnormal estrous cycle,decreased pregnancy rate and pathological changes of ovary in female rats;101 significantly differentially expressed genes(52 up-regulated genes and 49 down-regulated genes)were found in the ovarian tissue of SD rats,and 26 methylation significantly different regions were found between the SD50 group and the control group,but no changes in methylation levels were detected at all sites of the above 101 differentially expressed genes.The difference of fertility index of SD female rats showed that SD led to the decrease of fertility of female Wistar rats;The differentially expressed genes and methylation differences in the ovaries of SD rats indicate that SD may affect the gonadal function of female animals through gene transcription and epigenetic regulation.