大鼠孕期PM2.5和高温暴露对子代体重增长及甲状腺激素水平的影响OA
Effects of prenatal PM2.5 and heat exposure on offspring body weight gain and thyroid hormone levels in rats
[背景]大气细颗粒物(PM2.5)污染和全球变暖问题日趋严重,孕期 PM2.5 和高温暴露对胎儿及子代远期发育构成潜在威胁,但二者联合暴露对子代体格发育的影响及其机制尚不清楚. [目的]探究大鼠孕期 PM2.5 和高温单独及联合暴露对子代体重发育以及甲状腺激素(THs)水平的影响. [方法]本研究采用 8周龄 SPF级 Wistar大鼠作为实验对象,雌雄按 2∶1比例合笼交配.确认妊娠后,将 36只孕鼠随机分为 4组:PM2.5+高温组、PM2.5 暴露组、高温暴露组及对照组.PM2.5 暴露通过每日气管滴注法实施,每只大鼠滴注 2 mg·mL-1 的悬浮液 0.3 mL;高温暴露条件为(38.0±1.0)℃,每日暴露 1 h.所有暴露处理均自妊娠第 7日开始,持续至第 13日结束.仔鼠饲养至出生后第 42天(PND42),每周测量体重 2次.于 PND42采集血浆,采用酶联免疫吸附试验检测游离三碘甲状腺原氨酸(FT3)和游离甲状腺素(FT4)水平.采用线性混合效应模型分析 PM2.5 与高温暴露的交互作用对仔鼠体重及体重增量的影响,并采用单因素方差分析方法比较各时点仔鼠体重及 PND42时 THs水平的组间差异,采用 Spearman秩相关分析THs水平与体重变化的相关性. [结果]孕期 PM2.5 暴露以及 PM2.5 与高温联合暴露均与仔鼠部分发育时点体重升高相关:PM2.5 暴露组仔鼠在 PND7和 PND21时体重高于对照组,联合暴露组在 PND7及 PND21~35期间体重高于对照组(P<0.05),且上述体重变化在雌性仔鼠中更为明显.高温暴露组仔鼠出生体重低于其余各组(P<0.05),但随着发育该差异逐渐消失.PM2.5 暴露组仔鼠血浆 FT3 水平高于高温暴露组和对照组(P<0.05),但该差异仅在雌性仔鼠中具有统计学意义(P<0.05).仔鼠血浆 FT3水平与 PND7~42各时间点体重呈正相关,在全部仔鼠中相关系数为 0.316~0.539(P<0.05),在雌性仔鼠中为0.419~0.706(P<0.05),雄性仔鼠中未见统计学意义. [结论]孕期 PM2.5 暴露以及 PM2.5 与高温联合暴露可能影响仔鼠出生后的体重发育,该影响具有时间依赖性,且在雌性仔鼠中表现更为明显.孕期高温暴露与仔鼠出生体重降低及后续追赶性生长趋势有关.THs可能在孕期 PM2.5 与高温暴露影响雌性仔鼠体格发育中发挥重要作用,需进一步研究阐明.
[Background]The escalating challenges of fine particulate matter(PM2.5)pollution and global warming pose significant threats to human health.Previous studies have demonstrated that pre-natal exposure to PM2.5 and heat is associated with restricted fetal and offspring growth.Howev-er,the combined effects of co-exposure to PM2.5 and heat remain poorly understood,and the underlying biological mechanisms have yet to be elucidated. [Objective]To investigate the independent and combined effects of maternal exposure to PM2.5 and heat on offspring growth and thyroid hormone levels in rats. [Methods]Eight-week-old SPF Wistar rats were used.Females and males were mated at a 2:1 ratio.After confirming pregnancy,36 preg-nant rats were randomly assigned to four groups:combined PM2.5 and heat exposure,PM2.5 exposure,heat exposure,and control.PM2.5 exposure was administered via intratracheal instillation(0.3 mL,2 mg·mL-1)daily.Heat exposure was conducted in a programmable constant temperature and humidity chamber maintained at(38.0±1.0)℃for 1 h daily.Exposures were administered from gestational days(GD)7 to 13.Offspring were raised for 42 postnatal days(PND),with body weight measured twice weekly at fixed time points.On PND42,blood was collected to separate plasma for the measurement of free triiodothyronine(FT3)and free thyroxine(FT4)levels using enzyme-linked immunosorbent assay.Linear mixed-effects models were used to examine the interactive effects of PM2.5 and heat exposure on offspring body weight and weight gain.One-way analysis of variance was conducted to compare the differences in offspring body weight at each time point and thyroid hormone levels among groups.Correlations between thyroid hormone levels and weight changes were assessed using Spearman's rank correlation analysis. [Results]Both prenatal PM2.5 exposure alone and its combination with heat exposure were associated with higher offspring body weight at specific postnatal time points.Offspring in the PM2.5 exposure group had higher body weight than controls on PND7 and PND21,while those in the combined exposure group had higher body weight on PND7 and PND21-35(P<0.05),and this effect was stronger in female offspring.The heat exposure group showed significantly lower birth weight than other groups(P<0.05),but this difference gradually dis-appeared during development.Plasma FT3 levels were higher in the PM2.5 exposure group than in the heat exposure and the control groups(P<0.05),but this difference was statistically significant only in female offspring.Plasma FT3 levels were positively correlated with body weight from PND7 to PND42,with correlation coefficients of 0.316-0.539 in all offspring(P<0.05)and 0.419-0.706 in females(P<0.05),while no significant correlation was observed in males. [Conclusion]Prenatal exposure to PM2.5 alone or a combination of PM2.5 and heat may affect postnatal body weight gain in offspring in a time-dependent manner,with more pronounced effects observed in female offspring.Heat exposure alone leads to reduced early-stage weight followed by a trend toward catch-up growth.The findings suggest a specific role of thyroid hormones in the effects of prenatal PM2.5 and heat exposure on offspring growth,a relationship that warrants further investigation.
李慧君;王怀林;麦麦提敏江·吾拉音;卜玉媛;王琼
中山大学公共卫生学院,广东 广州 510080中山大学附属第八医院,广东 深圳 518033西安交通大学第二附属医院新疆医院(新疆维吾尔自治区人民医院白鸟湖医院),新疆 乌鲁木齐 830001中山大学公共卫生学院,广东 广州 510080中山大学公共卫生学院,广东 广州 510080
医药卫生
细颗粒物高温孕期体重发育甲状腺激素
fine particulate matterheat exposurepregnancybody weight developmentthyroid hormone
《环境与职业医学》 2026 (6)
762-768,7
国家自然科学基金项目(42475190,42075178) This study was funded.
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