The Potential Risk Assessment Of Hypertension Of ART Mice Offspring And Mechanism Research

Objective: Assisted reproductive technology is an effective means for the treatment of infertility.Since the first test-tube baby was born in 1978,the number of ART offspring has amounted to millions,and showed a trend of increasing year by year,the offspring's health has been paid more and more attention to.Compared with normal birth children,ART offspring suffer an increased risk of multiple pregnancy,premature birth,low birth weight,congenital malformations and genetic imprinting defects,whether the risk of cancer and metabolic syndrome increases is not clear yet.In this experiment,mice model were used to study the influence of ART on offspring's cardiovascular health.Using the offspring mice serum,myocardial and renal tissue,we preliminarily explore the possible mechanism leading to cardio-vascular anomalies of ART offspring.Methods: The C57 BL / 6(B6)female mice and DBA / 2(D2)males were used to get B6D2F1 mice(F1)as control group.Treatment group including: transplantation group(in vivo fertilization and embryo transfer),superovulation groups(stimulate ovulation and in vivo fertilization),IVF group(stimulate ovulation and in vitro fertilization-embryo transplantation)and IVM group(in vitro maturation of oocyte,in vitro fertilization-embryo transplantation).Each group of mice were randomly divided into three groups.Each group of mice respectively had blood pressure measuring in 8 weeks,24 weeks,40 weeks,and then used the eyeball blood collection method for whole blood.Then mice were sacrificed and organ/body weights were measured.The m RNA expression level of Agtr1 b in kidneys and Ece1 in cardiac muscle were measured with q-PCR.Western Blot was used to test the protein expression level of Ece1 in cardiac muscle.Results: Compared with normal group,8 weeks mice of transplantation group's systolic blood pressure increased,P < 0.05,statistically significant.Superovulation groups of 8 weeks(P < 0.05)and 40 weeks(P = 0.003)of female's systolic blood pressure were higher than normal group,and 24 weeks of male mice's systolic blood pressure had no difference with normal group.In IVF group,female in 40 weeks had a higher systolic blood pressure than normal group and transplantation group;systolic blood pressure of female in 8 weeks was higher than normal group;female in 24 weeks had a higher systolic blood pressure compared with transplantation group,P < 0.05,statistically significant.In the IVM group,systolic blood pressure of male mice in 40 weeks were higher than normal group(P = 0.003)and transplantation group(P < 0.05).Average pressure showed that,24 weeks of IVF group(P = 0.005)and superovulation groups(P < 0.05)in female were higher than normal group;40 weeks of IVF group's average pressure was higher than transplantation group in female mice,P<0.05,statistically significant.Diastolic blood pressure showed that,8 weeks of superovulation group was higher than normal group in male;24 weeks of female mice's diastolic blood pressure was higher than normal group;and 40 weeks of IVM group were higher than that of normal group in males and females,P < 0.05,statistically significant.The remaining groups of male and female had no statistical differences compared with normal group.In addition,40 weeks of females of IVF and the IVM heart body weight ratio is higher than normal group,P < 0.05,statistically significant.40 weeks age of male and female mice kidney Agtr1 b gene m RNA expression level had no difference between groups.In 40 weeks age of IVF male mice,Ece1 m RNA relative transcriptional level in cardiac muscle was higher than that of normal group and transplantation group,P < 0.05.40 weeks age of IVF female Ece1 relative transcriptional level was higher than the normal group,P < 0.05,statistically significant.In 40 weeks age of IVM female mice,Ece1 relative transcriptional level was higher than transplantation group(P = 0.004)and normal group(P < 0.05),suggesting that IVM and IVF female mice with older age may had an increasing level of Ece1 transcription in cardiac muscle tissue.In 40 weeks age of IVF male mice,myocardial Ece1 protein relative expression was higher than normal group(P = 0.003)and transplantation group(P = 0.001).In 40 weeks age of females,the relative expression of myocardial Ece1 protein IVF and IVM group were both higher than that of normal group,P < 0.05,statistically significant.Compared with the transplant group,the significance were also existed(P < 0.05).Conclusion: ART may affect the blood pressure of offspring mice,especially in old age mice;ART may cause the elderly female's heart weight ratio to increase;The blood pressure and heart weight ratio of ART mice increased may be related to the increasing level of myocardial Ece1 m RNA and protein expression;The ART had a greater impact on elderly female than male in Cardiovascular health.