Impact Of Chronic Intrauterine Hypoxia On Ovarian Reserve Of Rat Offspring

Objectives:1.To investigate the effects of fetal growth restriction(FGR)induced by chronic intrauterine hypoxia during pregnancy ovarian reserve at different developmental stages in offspring,based on the chronic intrauterine hypoxia model of SpragueDawley rats.2.To analyze the difference of miRNA expression profiles in the offspring ovarian tissues between the CIH group and the normal control group,and to explore the possible mechanism of these differentially expressed miRNA on ovarian reserve of rat offspring.Methods:Healthy female SD rats(n=20)were conceived by fertile male SD rats.On gestation day 3(GD3),pregnant SD rats were randomly divided into 2 groups:normal control group(n = 8)and CIH group(n = 12).The CIH group consisted of12 rats exposed to a hypoxia condition from gestational days 4 to 21.Four hours after hypoxia on the first day of hypoxia,4 pregnant rats were randomly selected from the normal controls group and the CIH group for arterial blood gas analysis.Body and ovary weight were measured in offspring rats.Histological observation and follicle count were performed on ovarian tissue sections of rat offspring.Differentially expressed miRNA in ovarian of CIH group and normal control group offspring female rats were screened by digital gene expression profiles.Results:1.CIH can lead to fetal growth restriction(P<0.05),but low birth weight progenies will catch-up growth during lactation(P<0.05).2.Compared with the normal control group,rats of CIH significantly depleted primordial follicles by 27.1% at postnatal day 5(PN5),40.0% at PN20 and 41.6% at PN40 in offspring(P<0.05).3.CIH programmed to 11 differentially expressed miRNA in ovarian of offspring female SD rats,including 5 up-regulations and 6 down-regulations.These miRNAs have been associated with cell proliferation,regulation,apoptosis and ovarian vascularization.Conclusions:CIH can diminish offspring ovarian reserve in rats.CIH programmed to differentially expressed miRNA in ovarian of offspring female SD rats,which might be the possible mechanism of CIH related the decline in ovarian reserve.