| Organochlorine pesticides are organic compounds that contain organochlorine elements used to control plant diseases and pests.Although the production and use of OCPs has been banned in China,OCPs can still be detected in a variety of environmental and biological media because of its strong anti-degradation ability and persistent existence in the environment.OCPs are lipophilic and bioaccumulative,which can be biologically enriched and biomagnified through the food chain and eventually enter animals and humans,which has a serious impact on the ecological environment and human health.Not only animal experiments have confirmed that OCPs has reproductive toxicity,immunotoxicity and carcinogenicity,but also many epidemiological studies have confirmed that the accumulation of OCPs in human body has adverse effects on health,including neurotoxicity,immunotoxicity,reproductive abnormalities,endocrine disorders,birth defects and even cancer.As a sensitive group of pregnant women,the level of OCPs exposure during pregnancy and its influencing factors are worth paying attention to.Telomere is a complex consisting of a specific binding protein and a TTAGGG hexanucleotide repeat sequence in tandem at the end of chromosomes of eukaryotic cells,which has the function of maintaining genome stability and chromosome integrity.With the increase of cell division times,the telomere length is shortened correspondingly.When the telomere length reaches a certain critical value,cells will undergo senescence or apoptosis.Therefore,telomere length can determine the cell lifespan.A large number of epidemiological studies have found that the shortening of telomere length is related to many aging-related diseases.In addition to normal shortening during cell division,telomere length is also affected by internal and external environmental factors.The individual difference of telomere length in adults is mainly determined by the telomere length of the newborn and the wear rate in the later stage of life,and the telomere length shortens faster in early life than in adulthood.Therefore,the factors related to the shortening of neonatal or initial telomere length have an important impact on the health status or disease occurrence of individuals,and neonatal telomere length can be used as an early biomarker of lifelong disease risk.However,the current studies on the influencing factors of telomere length are mainly limited to adults,and there are relatively few studies on the influencing factors of neonatal telomere length.The effect of intrauterine environmental exposure on neonatal telomere length has not been determined to a large extent.Therefore,this study conduct a prospective birth cohort study on the neonatal cord blood OCPs exposure level and its influencing factors,and further clarifies the association between prenatal OCPs exposure and telomere length in neonatal cord blood.Part Ⅰ Exposure level of organochlorine pesticides during pregnancy and its influencing factors.Objective: The purpose of this study is to analyze the exposure level of OCPs during pregnancy and its influencing factors.Methods: It selects 1035 pairs of mothers and infants recruited from Wuhan,China,as the research object.Neonatal cord blood samples are collected and nine OCPs()concentrations in cord blood are measured by liquid-liquid extraction combined with gas chromatography-tandem mass spectrometry.The OCPs content in serum is corrected by serum total lipid.The correlation between OCPs is evaluated,and the generalized linear model is used to analyze the possible influencing factors of OCPs exposure during pregnancy,including maternal age,pre-pregnancy BMI,maternal education level,parity,average annual family income,passive smoking during pregnancy,gestational diabetes mellitus,hypertensive disorder complicating pregnancy and infant gender.Results: The detection rates of various OCPs ranges from 14.1% to 100.0%,among which the detection rates of p,p′-DDE,β-HCH,α-HCH,γ-HCH,p,p′-DDD and p,p′-DDT are higher than 50%,and they are respectively 100.0%,99.8%,83.1%,80.5%,60.0% and 51.9%.Meanwhile,the concentrations of these six OCPs are also relatively higher,with a median of 33.90 ng/g,8.67 ng/g,0.22 ng/g,0.33 ng/g,0.12 ng/g and 0.15ng/g respectively.There is a weak positive correlation between the six major OCPs(rs=0.13-0.52,P<0.01).α-HCH,β-HCH,γ-HCH,p,p′-DDD,p,p′-DDE and p,p′-DDT are all positively correlated(P<0.01).The concentration of OCPs cord blood is significantly correlated with maternal age,pre-pregnancy BMI,maternal education level,parity,passive smoking during pregnancy and infant gender,and the influencing factors of different types of OCPs are also different.Conclusions: Pregnant women in Wuhan are widely exposed to OCPs,especiallyβ-HCH and p,p′-DDE.Maternal age,pre-pregnancy BMI,education level,parity,passive smoking during pregnancy and infant gender may affect OCPs concentration during pregnancy.Part Ⅱ Study on the association between organochlorine pesticide exposure during pregnancy and telomere length in neonatal cord bloodObjective:The study aims to investigate the association between the OCPs exposure concentration during pregnancy and telomere length in neonatal cord blood.Methods: In this part,based on 168 subjects whose OCPs have been detected in Part I,the cross-sectional design is adopted and the relative telomere length of neonatal cord blood leukocytes is measured by the method of fluorescence quantitative PCR.The six major OCPs(α-HCH,β-HCH,γ-HCH,p,p’-DDD and p,p’-DDE)converted by Log2 are correlated with the relative telomere length of cord blood leukocytes by the generalized linear regression model,and the possible confounding factors are adjusted.Stratified analysis is conducted to analyze the effect of infant gender(male,female),maternal age(< 25,25-30,≥30 years old)and pre-pregnancy BMI(< 18.5,18.5-24,≥24kg/ m2)on the association between OCPs concentration during pregnancy and telomere length in neonatal cord blood.Wald test is used to evaluate the interaction between different groups and serum OCPs concentration in cord blood on the telomere length of neonatal leukocytes.Results: 1.After correcting the concocting factors,telomere length is shortened by0.024(95% CI:-0.041,-0.007)for every two-fold increase of γ-HCH concentration in cord blood.No significant association between other OCPs and cord blood telomere length is observed.2.The results of gender stratification analysis show that,in male infants,the telomere length in cord blood is shortened by 0.042(95% CI:-0.070,0.014)for every two-fold increase of γ-HCH concentration during pregnancy.In female infants,the telomere length in neonatal cord blood is increased by 0.018(95%CI: 0.002,0.035),0.017(95%CI: 0.002,0.032),0.031(95%CI: 0.015,0.047)respectively for every two-fold increase of α-HCH,p,p′-DDD and p,p′-DD concentration during pregnancy.3.The results of maternal age stratification analysis show that,for pregnant women under 25 years old,the telomere length in cord blood is shortened by 0.025(95%CI:-0.040,-0.011),0.053(95%CI:-0.096,-0.010)and 0.384(95%CI:-0.701,0.067)respectively for every two-fold increase of α-HCH,p,p′-DDD and p,p′-DD concentration during pregnancy.For pregnant women from 25 to 30 years old,the telomere length in cord blood is shortened by 0.025(95%CI:-0.047,-0.003)for every two-fold increase of α-HCH concentration during pregnancy.4.The results of pre-pregnancy BMI stratification analysis show that,in the normal pre-pregnancy BMI group(18.5≦BMI<24kg/m2),the telomere length in cord blood is shortened by 0.027(95% CI:-0.049,-0.006)for every two-fold increase of γ-HCH concentration during pregnancy.In the overweight pre-pregnancy BMI group(BMI≥24kg/m2),the telomere length in cord blood is shortened by 0.111(95% CI:-0.203,-0.018)and 0.036(95% CI:-0.049,-0.023)respectively for every two-fold increase of β-HCH and p,p′-DDT concentration during pregnancy.Conclusions: There is an association between OCPs concentration during pregnancy and neonatal telomere length,which may be affected by the infant gender,maternal age and pre-pregnancy BMI.Whether OCPs exposure may have long-term harm to human health by affecting neonatal telomere length needs to be confirmed by future studies. |
PDF Full Text Request