Effect Of Cold Exposure On Reproductive Function Of Female Rats And Its Preliminary Mechanism

Background:The physiological function of the organism can often be affected by ambient temperature.Cold as an important environmental factor can damage many systems.Cold exposure poses a serious threat to public health,and is widely considered as a global challenge for human health.According to the epidemiological investigation,male and female have different sensitivities to cold.Cold can cause many adverse effects on female health.However,many of the mechanisms have not yet been revealed and systematically elaborated.Objective:Our aim was to evaluate the effects of cold exposure on the functions of the ovary and uterus and understand about the mechanisms in female rats.To simulate the effect of cold exposure on female menstrual cycle through the change of estrus cycle in female rats.Our aim is to observe the effects of cold exposure on the secretion level of hormones and the expression of related genes in female rats by morphological and molecular biological analyses.And to illustrate its possible mechanism of the endocrine disruption effect of cold exposure.Methods:The female SD rats were divided into two groups.The rats in control group were housed in standard temperature conditions(n=12),and those in the cold group were exposed to minus 10 ?,4 h per day for 2 weeks.During cold exposure,the animals' body weights,food and water consumption were measured.The estrous cycle of rats was examined by vaginal exfoliative cytology every day.At the end of the experiment the ovaries and uteri of each rat were dissected after euthanasia and weighed.The histopathological changes of the ovary and uterus of the female rats were observed by HE staining.And histomorphology of the uterus was performed to assess height of the luminal epithelium.The serum levels of estradiol(E2),luteinizing hormone(LH),follicle stimulating hormone(FSH),progesterone(P)and prolactin(Prl)were determined through radioimmunoassay using a kit.The gene expression levels of estrogen receptor(ER),luteinising hormone receptor(LHR),progesterone receptor(PR)and prolactin receptor(PrlR)in the ovary and uterus were tested by RT-qPCR.Results:(1)The observed body weight gain was relatively normal in the first week.Compared with the control group,the cold exposure group showed significantly reduced rates in body weight gain from day 8 to day 14(p < 0.05 and p < 0.01).The food and water consumption of the rats in cold group were significantly higher than those in control group(p < 0.05 and p < 0.01).The coefficients for the ovary and uterus showed no significant differences between the two groups(p > 0.05).(2)Significant changes were observed in each estrus cycle in the cold group compared with the control group.The estrus and diestrus phases were significantly increased after cold exposure(p < 0.05 and p < 0.01).However,the proestrus and metestrus phases showed no significant difference between the two groups.(3)The number of primordial follicles and primary follicles increased significantly in the ovaries of the cold group.We found a significant decrease in the diameter of the ovarian granular layer and theca cell layer in the cold group.And the lumen of the uterus was narrowed or connected,and the luminal epithelium of the intimal layer was irregular papillary in the uteri of the cold group.The endometrium and muscular layer showed edema and decreased or irregular shaped glands.Histomorphology study demonstrated that the uterine epithelium height in the cold group was significantly lower than that of the control group(p < 0.05).(4)Cold exposure caused a significant reduction serum P levels in female rats(p < 0.05).Compared with the control rats,the cold group has significantly higher level of serum LH(p < 0.05).Serum E2 and Prl in the cold group had a tendency to decrease.The level of serum FSH showed no significant differences between the two groups.(5)LHR mRNA expression was higher(p < 0.05)in the ovary in the cold-exposed female rats.A significant increase(p < 0.05)in PR mRNA expression was observed in the uterus of cold-exposed female rats.Cold exposure caused a significant reduction(p < 0.05)in the ER gene in the uterus.Conclusion:With the prolongation of cold exposure time,cold exposure can decrease the rats weight gain,increase food intake and water consumption.Cold exposure induced estrus cycle irregularity and some alterations in the morphology of the ovary.Cold exposure impairs the function of the ovary probably by changing the level of serum LH and increasing LHR expression.Cold exposure induced a significant reduction of uterine epithelium height.Cold exposure causes alterations in the morphology of the uterus probably because of the effect of progesterone,the increase in the PR level and the decrease in the ER level.