Continuous Light Exposure Influences The Luteinization And Luteal Function In Female Mice And Its Mechanism

In recent years,with the changes of people's lifestyle,more and more of the childbearing couples live with irregular schedules(i.e.staying up late)and suffer from decreased fertility and abortion.The relationship between the staying up late and fertility is still not exactly addressed,while previous studies clearly indicate continuous light exposure may disruptthe circadian rhythm of the female miceand cause melatonin secretion disorder.And moreover,the female mice are anovulatory and present polycystic ovarian morphology.Luteal phase defect(LPD),with an incidence of about 5%in women,is one of the most common endocrine diseases to cause abortion.The LPD patients usually represent luteinization disorder,inadequate progesterone secretion,menstrual cycle disorder and infertility.Melatonin is anantioxidant hormone secreted from pineal gland,and used to improve luteal function in clinic,while the mechanism is not still fully understood.In conclusion,the effects and mechanism of continuous light and melatonin on luteinization and luteal function are still unclear until now,and thus,should be investigatedObjective:To observe whether continuous light may affect luteinization and luteal function in female mice,and explore the effect and mechanism of melatonin on the luteal function of female mice under continuous light.Methods:In this study,the female mice under continuous light were used to simulate staying up late.Then,the changes of ovarian tissue were explored by HE staining,qRT-PCR,immunohistochemistry and western blotResearch contents:The experimental mice were divided into 4 groups:the control group,the continuous light group,the melatonin 1 mg/kg group and the melatonin 3 mg/kg group.From the 15th day of modeling,the melatonin groups were injected intraperitoneally with melatonin at the corresponding dose,lasting up to 42 days.After successful modeling,a series of experiments were conducted to study the effect of continuous light on the luteal formation and function in female mice,and to explore the effect of melatonin on the luteal function of female mice under continuous light and the specific mechanism.Results:This study found that,compared with the control group,the luteal retention time shortened(P<0.05),the level of progesterone in serum decreased(P<0.001),the number of luteal in ovary decreased(P<0.01),the expression of luteinization related genes(Lhcgr,Star,Ptgfr and Runx2)were down-regulation(P<0.05),the level of luteinization related proteins(CYP11A1 and SFRP4)decreased,the expression of clock genes(Clock and Per1)were down-regulation(P<0.05),the expression of Mt1 was down-regulation(P<0.05),and the level of MT1 protein decreased in the continuous light group female mice.Compared with the continuous light group,the luteal retention time prolonged(P<0.05),the level of progesterone in serum increased(P<0.001),the number of luteal in ovary increased(P<0.01),the expression of luteinization related genes(Lhcgr,Star,Ptgfr and Runx2)were up-regulation(P<0.05),the level of luteinization related proteins(CYP11A1 and SFRP4)increased,the expression of clock genes(Clock and Per1)were up-regulation(P<0.05),the expression of Mtl was up-regulation(P<0.05),and the level of MT1 protein increased in the melatonin 3 mg/kg group female mice.Furthermore,after 2 hours of hCG injection,the level of pERK protein in ovary decreased in the continuous light group,but increased in the melatonin 3 mg/kg group.Conclusion:Continuous light leads to shorten luteal retention time,reduce number of corpus luteum,and decrease progesterone secretion in female mice.Continuous light down-regulates the expression of Lhcgr,Star,Ptgfr,Runx2 and other genes in the ovary of female mice,inhibits the luteinization and reduces the secretion of progesterone.Continuous light may down-regulates the expression of Clock,Per1 and Mtl in the ovary of female mice,blocks ERK activation,thus inhibits the MAPK/ERK signaling pathway and reduces the luteinization.Melatonin is useful to promote luteinization in granulosa cells and improve luteal phase defect caused by dysrhythmia through activating the ERK directly or indirectly,and then activating MAPK/ERK signaling pathway.