Transgenerational effects and transmission mechanisms of paternal PM<sub>2.5</sub> exposure on growth and development in offspring

ZHANG Zhonghao; WANG Jiankang; HE Mengchao; SUN Lei; CHEN Qing; LIU Jinyi; CAO Jia

doi:10.16016/j.2097-0927.202502009

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Transgenerational effects and transmission mechanisms of paternal PM_2.5 exposure on growth and development in offspring

Monographic Reports | 更新时间：2025-07-27

- Transgenerational effects and transmission mechanisms of paternal PM_2.5 exposure on growth and development in offspring
- Journal of Army Medical University Vol. 47, Issue 15, Pages: 1741-1749(2025)
- 作者机构：
  
  1.陆军军医大学（第三军医大学）军事预防医学系军事毒理学教研室，重庆
  2.陆军军医大学（第三军医大学）防卫勤训练大队野战医学教研室，新疆呼图壁
- 作者简介：
  
  CAO Jia， E-mail： caojia1962@126.com
- 基金信息：
  
  the National Key Research and Development Program(2022YFC2702900);the Major Special Project for Four Major Chronic Diseases(2023ZD0519000)
- DOI：10.16016/j.2097-0927.202502009
  CLC： R122.7;R339.3;R394.1
- Received：06 February 2025，
  
  Revised：21 May 2025，
  
  Accepted：27 June 2025，
  
  Published：15 August 2025
- 稿件说明：
移动端阅览
张中豪，王建康，何孟超，等.父源PM_2.5暴露影响子代生长发育的跨代效应及传递机制研究［J］.陆军军医大学学报，2025，47（15）：1741-1749.DOI：10.16016/j.2097-0927.202502009.

ZHANG Z H，WANG J K，HE M C，et al.Transgenerational effects and transmission mechanisms of paternal PM_2.5 exposure on growth and development in offspring［J］.J Army Med Univ，2025，47（15）：1741-1749.DOI：10.16016/j.2097-0927.202502009.
张中豪，王建康，何孟超，等.父源PM_2.5暴露影响子代生长发育的跨代效应及传递机制研究［J］.陆军军医大学学报，2025，47（15）：1741-1749.DOI：10.16016/j.2097-0927.202502009. DOI：

ZHANG Z H，WANG J K，HE M C，et al.Transgenerational effects and transmission mechanisms of paternal PM_2.5 exposure on growth and development in offspring［J］.J Army Med Univ，2025，47（15）：1741-1749.DOI：10.16016/j.2097-0927.202502009. DOI：

摘要

目的

研究父源PM

2.5

暴露对子代生长发育影响的跨代效应，初步探讨精子DNA甲基化修饰在跨代传递中的作用。

方法

按简单随机分组法将8周龄C57BL/6雄鼠分为过滤空气（filtered air，FA）组、未过滤空气（unfiltered air，UA）组和浓缩环境PM

2.5

（concent

rated ambient PM

2.5

，CAP）组，每组10只，自2019年11月至2020年4月进行暴露。暴露结束后，与未暴露过PM

2.5

的正常雌鼠交配获得F1代，逐代繁殖到F2~F3代，所有子代饲养在无PM

2.5

环境中。记录子代的出生体质量、出生数量和性别比例，监测体质量增长情况，计算心脏、肝脏、肺脏和脑的脏器系数。对CAP组与FA组及其得到的F1代精子DNA进行全基因组甲基化测序，筛选差异甲基化区域，分析差异甲基化区域相关基因及通路。

结果

与FA组F1代相比，CAP组F1代小鼠出生体质量显著降低（

0.05），F2~F3代组间出生体质量无显著差异，未发现F1~F3代各组间性别比例和出生数量的显著改变。与FA组子代相比，CAP组F1~F3代体质量增长迟缓，且在雄性中更为显著（

0.05），CAP组F1代雄性小鼠肝脏器系数显著升高（

0.01），未发现F1~F3代各组间心脏、肺脏、脑系数的显著改变。CAP组与FA组相比检测到37 997个差异甲基化区域，其F1代差异甲基化区域的数量减少约50%。F0和F1代精子中的差异甲基化修饰基因可能与发育过程相关，其中包括印记基因（

Gnas

、

Igf2

）及代谢基因（

Ppard

、

Rps6kb1

）。

结论

父源PM

2.5

暴露可导致子代出生体质量下降及跨代生长迟缓，对表型效应的影响在代际传递过程中逐渐减弱，精子中发育相关基因的甲基化改变可能是介导此跨代效应的机制之一。

Abstract

Objective‍　‍To investigate the transgenerational effects of paternal PM

2.5

exposure on offspring growth and development

and to preliminarily elucidate the role of sperm DNA methylation modifications in mediating these effects. Methods‍　‍Eight-week-old male C57BL/6 mice were randomly divided into filtered air (FA)

unfiltered air (UA)

and concentrated PM

2.5

(CAP) groups

with 10 animals in each group. The exposure was conducted from November 2019 to April 2020

and then

these male mice were mated with unexposed females to generate F1 offspring

which were bred successively to produce F2 and F3 generations. All the offspring were living in PM

2.5

-free environment. The birth body weight

birth number

and sex ratio of the offspring were recorded

body weight growth was monitored

and organ coefficients of the heart

liver

lung

and brain were calculated. Whole-genome methylation sequencing was performed on the sperm DNA of the CAP group

FA group

and their F1 generation offspring to screen for differentially methylated regions

and the genes and pathways associated with

these regions were analyzed. Results‍　‍When compared with the F1~F3 offspring of the FA group

the CAP group had significantly reduced birth body weight in the F1 generation (

0.05)

no statistical differences were observed in the birth body weight in the F2 and F3 generations (

0.05)

or either in the sex ratio and birth number among the F1

F2 and F3 generations. Compared with the FA group offspring

the F1~F3 offspring of CAP group exhibited delayed body weight gain

especially in the males (

0.05)

the CAP-F1 male generation had obviously elevated liver organ coefficient (

0.01)

but no statistical changes were observed in the heart

lung

or brain coefficients among the F1~F3 generations. Between the FA group and the CAP group

37 997 differentially methylated regions were detected

with a reduction of approximately 50% in the number of differentially methylated regions in the F1 generation. Differentially methylated genes in F0 and F1 sperm were potentially related to developmental processes

including imprinting genes (

Gnas

Igf2

) and metabolic genes (

Ppard

Rps6kb1

). Conclusion‍　‍Paternal exposure to PM

2.5

leads to reduced birth weight and intergenerational growth retardation in offspring. Its impact on phenotypic effects is gradually weakened during intergenerational transmission. Changes in the methylation of development-related genes in sperm may be one of the mechanisms mediating this intergenerational effect.

关键词

Keywords

references

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Transgenerational effects and transmission mechanisms of paternal PM2.5 exposure on growth and development in offspring

DOI：10.16016/j.2097-0927.202502009

摘要

Abstract

关键词

Keywords

references

Transgenerational effects and transmission mechanisms of paternal PM_2.5 exposure on growth and development in offspring