Effects Of Gen-X Exposure During Pregnancy On Thyroid Function In Pregnant Rats And Development In Their Offspring

BackgroundHexafluoropropylene oxide dimer acid(HFPO-DA,trade name Gen-X)is a new alternative compound as a straight chain perfluoroalkyl material(PFAS)and Perfluorooctanoic acid(PFOA).Because of its unique short chain structure,short halflife and low accumulation in living organisms that the current society is widely used in chemical and daily necessities manufacturing industry.However,there is a lack of sufficient evidence and researches on the harm or potential risks of human and ecological environment,especially for high-risk groups such as pregnant,maternal and children.Therefore,the potential harm and possible mechanism of Gen-X have attracted great attention from the whole society.ObjectiveThe present study investigated the effects of Gen-X exposure on thyroid function in gestational rats and development of offspring fetal rats.The objective is to provide evidence for exploring the potential risks and effects of Gen-X exposure on pregnancy,maternal and newborn.MethodsSprague-Dawley(SD)rats at gestation days(GD)0.5 were randomly divided into 4groups: control(without Gen-X),low(1 mg/kg),medium(10 mg/kg)and high dose group(100 mg/kg),with 8 rats in each group.During GD0.5-19.5,pregnant rats were given Gen X daily following the prescribed doses.All rats were euthanized on GD19.5and the serum of pregnant rats was collected by heart puncture.Then,the fetal birth weight,body length and tail length were measured and recorded.Thyroid tissue morphology was observed by hematoxylin and eosin staining for observe and evaluate the pathological changes;The levels of maternal serum thyroid stimulating hormone(TSH),total tetraiodothyronine(TT4)and total triiodothyronine(TT3)were detected using ELISA kits,and the level of maternal serum Gen X was detected by HPLCMS/MS.Results1 Effect of Gen-X exposure during pregnancy on growth and development of their offspringCompared with the control group,the birth weight,body length and tail length of fetal rats decreased with the increase of exposure dose,showing an obvious negative correlation.In addition,the birth weight,body length and tail length of fetal rats after Gen-X exposure in 100mg/kg group were significantly decreased,and the difference was statistically significant(P<0.05).2 Determination of Gen-X in serum of pregnant ratsThe results of the determination of Gen-X in the serum of pregnant mice showed that the serum Gen-X level was positively correlated with the exposure dose.Compared with the control group,the average level of serum Gen-X in 10mg/kg and 100mg/kg dose groups was significantly increased(P < 0.05),and the difference was statistically significant.3 Effects of Gen X exposure during pregnancy on thyroid function in pregnant ratsThe results of thyroid hormone levels in the blood of pregnant rats suggested that the thyroid hormone TSH levels in the 10mg/kg and 100mg/kg dose groups were significantly increased(P < 0.05),and the difference was statistically significant.In100mg/kg dose group,TSH,TT3 and TT3/TT4 ratio levels were significantly increased(P<0.05),and the differences were statistically significant.But no significant difference was found in TT4 test results among all dose groups(P > 0.05).It was found that pathological sections of thyroid tissue of pregnant mice suggested that thyroid tissue morphologies were changed in the Gen-X exposure group of100mg/kg.Compared with the control group and the medium-low dose group,it was found that part of thyroid follicular cavities were reduced,thyroid follicular glia were reduced and thyroid follicular hyperplasia was observed.Conclusion100mg/kg dose HFPO-DA exposure caused maternal thyroid hormone to be disturbed by damaging the thyroid microstructure,and thus lead to intrauterine growth retardation of offspring.