邻苯二甲酸酯暴露与女性生殖健康

doi:10.19586/j.2095-2341.2025.0143

生物技术进展 ›› 2026, Vol. 16 ›› Issue (1): 68-75.DOI: 10.19586/j.2095-2341.2025.0143

邻苯二甲酸酯暴露与女性生殖健康

赵靖舒¹(), 李欢¹, 杜盈萱¹, 崔静雅², 张东煜¹, 罗云耀¹, 宋昊柯¹, 隋宏书¹(), 马文龙³(), 孙雨彤¹(), 杨艳⁴()

^1.山东第一医科大学临床与基础医学院组织学与胚胎学系，济南 250117
^2.山东第一医科大学口腔医学院，济南 250117
^3.山东第一医科大学药学院，济南 250117
^4.山东第一医科大学临床与基础医学院形态学实验室，济南 250117

收稿日期:2025-10-16 接受日期:2025-11-28 出版日期:2026-01-25 发布日期:2026-02-12
通讯作者: 隋宏书,马文龙,孙雨彤,杨艳
作者简介:赵靖舒 E-mail:2190461955@qq.com
基金资助:
国家自然科学基金项目(81670004);山东第一医科大学校级大学生创新创业训练计划项目(2025104391049)

Phthalate Exposure and Female Reproductive Health

Jingshu ZHAO¹(), Huan LI¹, Yingxuan DU¹, Jingya CUI², Dongyu ZHANG¹, Yunyao LUO¹, Haoke SONG¹, Hongshu SUI¹(), Wenlong MA³(), Yutong SUN¹(), Yan YANG⁴()

^1.Department of Histology and Embryology，College of Clinical and Basic Medicine，Shandong First Medical University，Jinan 250117，China
^2.College of Stomatology，Shandong First Medical University，Jinan 250117，China
^3.College of Pharmacology，Shandong First Medical University，Jinan 250117，China
^4.Morphology Laboratory，College of Clinical and Basic Medicine，Shandong First Medical University，Jinan 250117，China

Received:2025-10-16 Accepted:2025-11-28 Online:2026-01-25 Published:2026-02-12
Contact: Hongshu SUI,Wenlong MA,Yutong SUN,Yan YANG

摘要/Abstract

摘要：

邻苯二甲酸酯(phthalate esters，PAEs)是一类广泛存在的环境内分泌干扰物，可通过多种途径导致人群普遍暴露，对女性生殖健康构成显著威胁。目前流行病学研究结果尚不一致，PAEs对卵巢、子宫及妊娠结局的毒性机制仍未完全阐明，限制了风险精准评估与防控策略的制定。系统总结了PAEs的人体暴露特征，重点探讨了其通过干扰多种激素平衡与信号通路介导的多重生殖毒性，包括抑制卵泡发生、降低抗苗勒管激素水平及扰乱类固醇生成；增加多囊卵巢综合征风险；促进子宫平滑肌瘤增殖与内膜异位症侵袭；并显著增加胚胎着床障碍、胎盘发育异常、妊娠丢失和早产等不良结局风险。整合多学科证据，系统解析了PAEs的作用机制，为全面评估其对女性的生殖风险及制定针对性干预措施提供了科学依据。

关键词: 邻苯二甲酸酯, 女性生殖健康, 内分泌干扰

Abstract:

Phthalate esters （PAEs） are a class of widely distributed environmental endocrine disruptors that can lead to widespread human exposure through multiple pathways， posing significant threats to female reproductive health. Current epidemiological findings remain inconsistent， and the toxic mechanisms of PAEs on the ovaries， uterus， and pregnancy outcomes have not yet been fully elucidated， which limits accurate risk assessment and the development of prevention and control strategies. This review systematically summarized the characteristics of human exposure to PAEs， with a focus on their multifaceted reproductive toxicity mediated by disrupting various hormonal balances and signaling pathways. Key manifestations and mechanisms include inhibiting folliculogenesis， reducing anti-Müllerian hormone levels， disrupting steroidogenesis， increasing the risk of polycystic ovary syndrome， promoting the proliferation of uterine leiomyomas and the invasion of endometriosis， as well as significantly elevating the risks of adverse outcomes such as embryo implantation failure， abnormal placental development， pregnancy loss， and preterm birth. By integrating multidisciplinary evidence， this study systematically deciphered the mechanisms of action， providing a scientific basis for comprehensively assessing the female reproductive risks associated with PAEs and formulating targeted intervention measures.

Key words: phthalates, female reproductive health, endocrine disruption

中图分类号:

Q492

赵靖舒, 李欢, 杜盈萱, 崔静雅, 张东煜, 罗云耀, 宋昊柯, 隋宏书, 马文龙, 孙雨彤, 杨艳. 邻苯二甲酸酯暴露与女性生殖健康[J]. 生物技术进展, 2026, 16(1): 68-75.

Jingshu ZHAO, Huan LI, Yingxuan DU, Jingya CUI, Dongyu ZHANG, Yunyao LUO, Haoke SONG, Hongshu SUI, Wenlong MA, Yutong SUN, Yan YANG. Phthalate Exposure and Female Reproductive Health[J]. Current Biotechnology, 2026, 16(1): 68-75.

图/表 1

参考文献 35

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靶向功能	过程	主要毒性效应	关键证据/生物标志物	潜在核心机制
卵巢功能	卵泡发生与储备	卵巢储备功能下降	尿液中MMP、MiBP、MEHP水平升高；血清AMH水平降低、FSH水平升高	干扰PI3K/AKT、MAPK通路；影响DNA损伤修复基因；表观遗传改变
	类固醇生成	激素紊乱，排卵障碍	血清雌二醇、孕酮水平异常	抑制CYP19A1、STAR等关键酶表达；干扰cAMP、ERK1/2信号
	多囊卵巢综合征	增加PCOS风险严重程度	PCOS患者尿液中多种PAEs代谢物水平升高与雄激素等呈正相关	干扰HPO轴功能；诱导胰岛素抵抗
子宫健康	子宫平滑肌瘤	促进肌瘤发生与存活	DEHP暴露与风险正相关；MEHHP水平与细胞存活率相关	激活色氨酸-犬尿氨酸-AHR信号通路
子宫健康	子宫内膜异位症	增强内膜细胞侵袭与存活能力	患者尿液中DEHP代谢物水平高；异位病灶体积增大	提升MMPs活性；激活NF-κB、STAT3炎症通路
妊娠结局	胚胎着床与胎盘发育	着床失败，胎盘功能异常	动物模型中着床率下降；胎盘血管生成因子表达下调	改变GATA6、CDX2表达；引起胎盘表观遗传改变
妊娠结局	妊娠维持	妊娠丢失、早产风险增加	流产女性尿液中MEP、MBP等浓度高；早产与MEHP、MECPP相关	诱导氧化应激与炎症反应；干扰子宫内膜容受性

靶向功能	过程	主要毒性效应	关键证据/生物标志物	潜在核心机制
卵巢功能	卵泡发生与储备	卵巢储备功能下降	尿液中MMP、MiBP、MEHP水平升高；血清AMH水平降低、FSH水平升高	干扰PI3K/AKT、MAPK通路；影响DNA损伤修复基因；表观遗传改变
	类固醇生成	激素紊乱，排卵障碍	血清雌二醇、孕酮水平异常	抑制CYP19A1、STAR等关键酶表达；干扰cAMP、ERK1/2信号
	多囊卵巢综合征	增加PCOS风险严重程度	PCOS患者尿液中多种PAEs代谢物水平升高与雄激素等呈正相关	干扰HPO轴功能；诱导胰岛素抵抗
子宫健康	子宫平滑肌瘤	促进肌瘤发生与存活	DEHP暴露与风险正相关；MEHHP水平与细胞存活率相关	激活色氨酸-犬尿氨酸-AHR信号通路
子宫健康	子宫内膜异位症	增强内膜细胞侵袭与存活能力	患者尿液中DEHP代谢物水平高；异位病灶体积增大	提升MMPs活性；激活NF-κB、STAT3炎症通路
妊娠结局	胚胎着床与胎盘发育	着床失败，胎盘功能异常	动物模型中着床率下降；胎盘血管生成因子表达下调	改变GATA6、CDX2表达；引起胎盘表观遗传改变
妊娠结局	妊娠维持	妊娠丢失、早产风险增加	流产女性尿液中MEP、MBP等浓度高；早产与MEHP、MECPP相关	诱导氧化应激与炎症反应；干扰子宫内膜容受性

邻苯二甲酸酯暴露与女性生殖健康

Phthalate Exposure and Female Reproductive Health

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