Regulation Of Oxytocin Receptor(OXTR) Overexpression On Adipose Tissue Development,Energy Metabolism And Reproduction

With the development of economy and social modernization,incidence of obesity and infertility are increasing in China and globally.Accumulation of excessive adipose tissue leads to obesity.One of the main causes of female infertility is ovulation disorder.Investigation of key regulators in metabolic process and infertility is ever demanding.OXTR,a receptor of oxytocin,plays an important role in many aspects including reproductive lactation,social function,maternal behavior and energy metabolism.Absence of OXTR leads to variety of diseases.However,the effect of OXTR over expression has never been studiedIn order to explore the effects of over-expressed OXTR on development of mouse adipose tissue,energy metabolism and reproduction,we used a transgenic technology to generate a stable OXTR over-expressed transgenic mouse model(⁺⁺Oxtr).The experimental investigation found that the growth and reproduction of male⁺⁺Oxtr mice were grossly normal.When compared with wild-type mice,the body weight of⁺⁺Oxtr mice was lighter and body temperature was higher with a same food intake.The basal metabolic rate is higher.Histology study on adipose tissues found that⁺⁺Oxtr mice had less fat accumulation.Tissue section and H&E staining results showed that⁺⁺Oxtr mice had smaller white fat cells.Further study shown that OXTR overexpression induced up-regulation of the brown adipose-associated genes in white adipose tissue,causing browning of white adipose.⁺⁺Oxtr females showed no abnormal growth but impaired fertility.⁺⁺Oxtr female showed abnormal ovulation during the entire reproductive process,but their uterine function was not significantly impaired.Tissue sections of ovary tissues of female⁺⁺Oxtr mice were found to have cystic follicles and abnormally high expression of genes related to follicular development and ovulation.Therefore,we speculated that overexpression of OXTR induced the formation of cystic follicles,a similar disease that causes infertility in human.⁺⁺Oxtr mice cannot ovulate normally and have reproductive disorders.In this study,we used a transgenic mouse model of OXTR overexpression and found that overexpressing OXTR can regulate adipose tissue development and energy metabolism in male mice,and impair development of ovarian follicles and ovulation,revealing its new biological functions.These studies are important for prevention and cure of male obesity and female infertility.They provide new potential drug targets and may have important clinical application value.