| Background BPA is a common plasticizer material,especially suitable for the industrial production of phenol and epoxy resins and polycarbonate plastics,and is commonly used to make many common items in our lives.In our daily lives,the main way BPA is exposed is through dietary exposure into the body.Recent studies have shown that BPA exposure during prenatal pregnancy will lead to changes in the intestinal flora of offspring,a decrease in the level of short-chain fatty acid-producing bacteria,and the change of short-chain fatty acid level can affect short-chain fatty acid-G protein-coupled receptor signaling,thereby changing the functional differentiation and permeability of the embryonic intestine,resulting in metabolic disorders and other related phenotypes in the later life of the body.Objective 56-day specific pathogen free(SPF)grade C57BL/6N WT male female mice were selected,and after one week of adaptive rearing,the ratio of one male and two females per cage was taken to check the pubic plug,and the confirmed pregnant female mice were randomly divided into six groups: 0.01% DMSO,10 n M BPA,100 n M BPA,1000 n M BPA,HFiD+DMSO,HFiD+1000n M,The experiment was carried out in two parts: the first part of the embryonic offspring experiment had at least six pregnant mice in each group,and the subsequent lactating adult sub-mouse experiment set up at least ten pregnant mice in each group.Female mice were given BPA exposure through drinking water from the first day of confirmed pregnancy to delivery,dietary fiber supplementation(dietary inulin)was given to the high-fiber diet intervention group,and the rest of the groups were given a normal diet,while each group was paired with a surrogate group according to the time of pregnancy,and the female mice who were not exposed to BPA were substituted for three weeks after delivery,and the female mice were given normal diet feeding during lactation,and randomly divided into two groups after the offspring reached three weeks.High-fat diet and normal diet were given up to19 W by sex.The embryos in the abdomen were dissected one day before the birth of the mother,and the offspring were dissected at 3W and 19 W time points for experiments: gene expression detection related to intestinal differentiation and development,intestinal permeability detection,plasma enteroendocrine hormone PYY,GLP-1 content detection and lipid metabolism index detection.At the same time,the weight and growth status of offspring are continuously recorded.Research methods Select 56 day old C57BL/6N WT male and female mice of specific pathogen free(SPF)grade,and after adaptive feeding for one week,adopt the ratio of one male to two female per cage to check the yin suppository.The confirmed pregnant female mice were randomly divided into six groups: 0.01% DMSO,10 n M BPA,100 n M BPA,1000 n M BPA,HFiD+DMSO,and HFiD+1000 n M.The experiment was conducted in two parts:The first part discusses the effects of BPA exposure during pregnancy on the intestinal development and function of fetal rats.At least six pregnant rats in each group were exposed to BPA through drinking water from the first day of pregnancy until GD18.5,with a normal diet;The high fiber diet intervention group was given dietary fiber supplementation(dietary inulin supplementation).GD18.5: Fetal mice were dissected and used for experiments: detection of gene expression related to intestinal differentiation and development,detection of intestinal permeability,detection of plasma levels of intestinal endocrine hormones PYY and GLP-1 in offspring,and detection of lipid metabolism indicators.The second part explores the effects of BPA exposure during pregnancy on the development and function of the offspring’s intestines,as well as the relationship between BPA exposure and abnormal lipid metabolism in the offspring’s adulthood.At least ten pregnant rats were set up in each experimental group,and BPA exposure was given through drinking water from the first day of pregnancy confirmation to delivery,with a normal diet;The high fiber diet intervention group was given dietary fiber supplementation(dietary inulin supplementation).After birth,the offspring were fed a normal diet and were not exposed to BPA.The offspring were raised to wean for three weeks.After weaning,the offspring were randomly divided into a high fat diet and a normal diet group,and were fed HFD and NCD until 19 W,respectively.The offspring were harvested at 3W and 19 W time points for experiments: detection of gene expression related to intestinal differentiation and development,detection of intestinal permeability,detection of plasma levels of intestinal endocrine hormones PYY and GLP-1 in offspring,and detection of lipid metabolism indicators.Results1.BPA exposure during pregnancy will affect the intestinal development,differentiation and permeability of offspring.Compared with the control group,the expression of PAX4,PAX6 and CDX2 mRNA genes related to intestinal development and differentiation in the BPA exposure group during embryonic and lactation gradually decreased with the increase of dose,and the expression of PAX4,PAX6 and CDX2 mRNA decreased significantly in the1000 n M BPA group compared with the control group(P <0.05),this effect persisted in the high-fat diet-fed group in adulthood until 19 W in adulthood.At the same time,histopathological observation showed that BPA exposure during pregnancy also led to increased intestinal permeability in offspring,and the expression of intestinal tight junction protein TJP-1 mRNA in the 1000 n M BPA exposure group decreased significantly(P<0.05)compared with the control group,and this change continued until19 W in adulthood in the high-fat diet feeding group of offspring.2.BPA exposure during pregnancy will affect the secretion and expression of intestinal endocrine hormones PYY and GLP-1 in offspringCompared with the control group,the contents of enteral endocrine hormones PYY and GLP-1 in the offspring of the BPA exposure group gradually decreased with the increase of dose compared with the control group,and the content of intestinal endocrine hormone GLP-1 decreased significantly in the 1000 n M BPA group compared with the control group(P<0.05),and this effect continued until 19 W in the high-fat diet feeding group in adulthood,and at 19 W,the plasma content of PYY and GLP-1 in male offspring decreased statistically significantly in the 1000 n M BPA group compared with the control group(P <0.05),while only the female offspring had a statistically significant decrease in plasma GLP-1 content(P<0.05).3.BPA exposure during pregnancy promotes HFD-induced lipid metabolism abnormalities in adulthood in offspringThere were no obvious metabolic disorders in the offspring of 3W in the BPA exposure group during pregnancy,and there were no significant differences in lipid metabolism-related indexes TG,T-CHO,HDL-C,LDL-C,LEP,ADPN and females in the offspring general diet group after feeding to 19 W.The test results of the subsequent offspring in the adult high-fat diet feeding group were 19W;The contents of plasma TG,T-CHO,LDL-C,LEP and ADPN in male offspring showed a gradual increase trend with the increase of exposure dose during pregnancy,and the plasma contents of TG,T-CHO and ldl-C in the 1000 n M BPA group were statistically different from the control group(P<0.05),while the plasma HDL-C content decreased with the increase of the exposure dose during pregnancy,and the difference in plasma HDL-C content in the1000 n M BPA group compared with the control group was statistically significant(P<0.05)。Similar to males,lipid metabolism indexes TG,T-CHO,LDL-C,HDL-C,LEP, AND ADPN showed similar trends and statistical differences at 19 W in female offspring.In general,under the induction of HFD,the offspring of male females in adulthood showed a phenotype related to lipid metabolism disorders in the BPA exposure group during pregnancy,and there was a dose-response relationship.4.High-fiber dietary intervention during pregnancy can improve BPA intestinal development and permeability changes induced by exposure during pregnancy.In the high-fiber diet intervention group,the expression of PAX4,PAX6,CDX2 mRNA and the expression of TJP-1 mRNA of intestinal tight junction protein TJP-1mRNA in the 1000 n M BPA+HFiD group were significantly increased compared with the 1000 n M BPA exposure group at the embryonic stage,and the differences were statistically significant(P <0.05)。 At the same time,the expression of PAX4,PAX6,CDX2 mRNA and the expression of TJP-1 mRNA of intestinal nexus protein TJP-1 in male female offspring during lactation were increased,and the expression of PAX4,PAX6,CDX2 mRNA and TJP-1 mRNA of intestinal nexus protein TJP-1 mRNA in the1000 n M BPA+HFiD group were significantly increased(P <0.01)。 The length and density of the small intestinal villi also improved significantly.In the subsequent adult high-fat diet feeding group,the expression of PAX4,PAX6,CDX2 mRNA and the expression of intestinal nexus TJP-1 mRNA in the offspring male and female offspring were still increased,and compared with the 1000 n M BPA exposure group,the expression of intestinal developmental differentiation-related genes PAX4,PAX6,CDX2 mRNA and the intestinal nexus protein TJP-1 in the 1000 n M BPA+HFiD group were still increased The expression of mRNA was significantly increased(P<0.01).5.High-fiber dietary intervention during pregnancy can improve the effect of BPA exposure during pregnancy on the secretion and expression of intestinal endocrine hormones PYY and GLP-1 in offspring.In the high-fiber diet intervention group,the contents of enteroendocrine hormones PYY and GLP-1 in the embryonic stage of the high-fiber intervention group were increased,and compared with the 1000 n M BPA exposure group,the plasma GLP-1content of the 1000 n M BPA+HFiD group increased statistically significantly(P<0.05),while the plasma contents of enteral endocrine hormones PYY and GLP-1 in the male and female offspring of the high-fiber intervention group during lactation were increased,and compared with the 1000 n M BPA exposure group,the plasma GLP-1content of male and female offspring in the 1000 n M BPA+HFiD group increased statistically significantly(P <0.05)。In the subsequent adult high-fat diet feeding group,the contents of enteral endocrine hormones PYY and GLP-1 in the plasma of male and female offspring in the high-fiber intervention group were increased,and compared with the 1000 n M BPA exposure group,the plasma plasma PYY and GLP-1 contents of male offspring in the 1000 n M BPA+HFiD group were significantly increased(P<0.05),and the plasma GLP-1 content of female offspring was increased statistically significantly(P<0.05)。6.High-fiber diet intervention during pregnancy can improve BPA lipid metabolism abnormalities in adult-induced high-fat feeding offspring induced by exposure during pregnancy.The study found that during lactation,the plasma contents of TG,T-CHO,LDL-C,HDL-C,LEP and ADPN in each group did not show significant changes and did not produce lipid metabolism-related phenotypes,while the plasma lipid metabolism index detection in the adult high-fat feeding group found that after the introduction of HFiD dietary intervention in the male female offspring of the 1000 n M BPA dose group and the DMSO group,the plasma content of TG,T-CHO,LDL-C,LEP and ADPN decreased,HDL-C content increased.Compared with 1000 n M BPA and 1000 n M BPA,the plasma contents of TG,T-CHO,LDL-C and hdl-C in male and female offspring were statistically significant(P<0.05),and the plasma LEP and ADPN contents only showed a downward trend but no statistical difference.The experimental results showed that the intervention of high-fiber diet during pregnancy could correct and improve the lipid metabolism disorders mediated by BPA exposure during pregnancy in the high-fat feeding group of offspring,and make the lipid metabolism indexes close to the control group DMSO,and this trend appeared in both male and female offspring.Conclusions1.BPA exposure during pregnancy affects the intestinal development of offspring,as well as the secretion and expression of intestinal endocrine hormones PYY and GLP-1,and these changes are related to abnormal lipid metabolism in adulthood in offspring.2.High-fiber diet during pregnancy can significantly improve the effect of BPA exposure during pregnancy on intestinal development and intestinal permeability and intestinal endocrine hormone expression in adulthood high-fat feeding offspring,thereby improving metabolic abnormalities in adulthood... |
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