Mechanism Of Androgen Programming During Pregnancy In Offspring Rats Obesity

ObjectiveThis study was to explore the role of androgen programming during pregnancy in the occurrence of offspring obesity,and to provide a theoretical basis for further understanding the mechanism of obesity.MethodTaking SD rats as the research object,20 pregnant female SD rats were randomly divided into two groups:the intervention group?T group,N=10?was given testosterone intervention at the third week of pregnancy?subcutaneous injection of 2ml of 2.5g/L testosterone solution?olive oil as the solvent?in the neck back,4 injections every other day?,and the control group?C group,N=10?was given olive oil in equal amounts.Normal feed was given to the offspring rats and weaned 3 weeks later.32 offspring rats in group T?half male and female?,of which 16?half male and female?were fed with normal feed?T+C group?,16 were fed with high-fat diet?T+HF group?;32 offspring rats in group C?half male and female?,of which 16?half female and male?were fed with normal feed?C+C group?and 16 were fed with high-fat feed?C+HF group?.The offspring rats were killed after 13 weeks of feeding.Body weight,abdominal fat and other morphological indicators were measured.Blood samples of rats were collected and serum sex hormones and biochemical indexes were detected.And the hypothalamus,pituitary,liver,kidney and adipose tissue were collected for immunohistochemistry,RT-PCR and Western blot to detect the mRNA and protein expression levels of appetite regulation,lipid production/metabolic factors in hypothalamus,pituitary and adipose tissue.One-way analysis of variance?LSD-t test as multiple comparisons?and 2×2 factorial design analysis of variance were used for statistical tests.Results1.In male offspring rats,abdominal fat and abdominal fat coefficient increased after testosterone intervention during pregnancy?P<0.05?;After the high-fat diet was given to the offspring,the abdominal fat and abdominal fat coefficient were increased?P<0.05?.There was an interaction between testosterone intervention during pregnancy and high-fat diet intervention on abdominal fat and abdominal fat coefficient(P_T*HF<0.05).After testosterone intervention during pregnancy,the offspring were given high-fat diet intervention again,and the accumulation of abdominal fat was more obvious.2.The testosterone intervention during pregnancy increased the anal genital distance?AGD?of female offspring?P<0.05?,and increased in abdominal fat and abdominal fat coefficient after pregnancy testosterone intervention+high-fat diet intervention?P<0.05?.3.Testosterone intervention during pregnancy increased sex hormone binding globulin?SHBG?in offspring male rats,and decreased free testosterone?FT?,dehydroepiandrosterone?DHEA?,and gonadotropin-releasing hormone?GnRH??P<0.05?;High-fat intervention increased the cholesterol and high-density lipoprotein?HDL?of male offspring,and the GnRH decreased?P<0.05?.4.Testosterone intervention during pregnancy increased blood glucose in female offspring,and high-fat diet intervention reduced triglyceride?TG??P<0.05?.5.Immunohistochemistry showed that testosterone intervention and high-fat diet intervention reduced the expression of leptin receptor?LEPR?and kisspeptin in the hypothalamus of offspring rats.Conclusion1.Androgen exposure during pregnancy could promote the occurrence of obesity in offspring rats,and this effect was more obvious after the testosterone intervention during pregnancy and the high-fat diet environment exposed to offspring.2.Testosterone intervention during pregnancy inhibited GnRH release,LEPR and kisspeptin expression,which resulted in the suppression of the hypothalamic appetite suppression center,and played an important role in the occurrence of obesity.