孕期暴露邻苯二甲酸酯对胎盘功能的影响及其机制研究进展

doi:10.3969/j.issn.1674-8115.2021.09.020

摘要/Abstract

摘要：

邻苯二甲酸酯（phthalates，PAEs）在生活中广泛存在，是一类典型的环境内分泌干扰物（environmental endocrine disruptors，EEDs）。胎盘富含激素受体，使其对EEDs高度敏感。孕期暴露于PAEs，其代谢物可以透过胎盘，通过干扰激素受体影响胎盘功能。胎盘功能障碍将导致胎儿生长受限，甚至引起胎儿死亡。孕期PAEs暴露与胎盘功能异常相关的机制包括侵润/融合、氧化应激、细胞分化/凋亡、激素分泌和脂质积累等。该文总结了孕期PAEs暴露水平概况，综述PAEs对胎盘功能的影响及相关研究进展，并探讨当前研究可能存在的局限性，为未来深入研究PAEs影响胎盘功能的分子机制提供参考。

关键词: 邻苯二甲酸酯, 环境内分泌干扰物, 孕期暴露, 胎盘功能障碍

Abstract:

Phthalates (PAEs) are widespread in life and are a class of environmental endocrine disruptors (EEDs). The abundance of hormone receptors makes the placenta highly sensitive to EEDs. During pregnancy, women can be exposed to PAEs, and their metabolites can pass through the placenta and affect its function by interfering with hormone receptors.The dysfunction of placenta will result in fetal growth restriction or, if more severe, fetal death. Functional placental disruptions linked to phthalates exposures include invasion/migration, oxidative stress, cell differentiation/apoptosis, hormone secretion and lipid accumulation.In this paper, the exposure level of PAEs during pregnancy is summarized, the mechanism for the effect of phthalates on placenta is reviewed, and the possible limitations of these studies are discussed, aiming to provide insights for further studies on the potential molecular mechanism through which PAEs disrupt placental function.

Key words: phthalate (PAE), environmental endocrine disruptor (EED), prenatal exposure, placental dysfunction

中图分类号:

张前龙, 田英. 孕期暴露邻苯二甲酸酯对胎盘功能的影响及其机制研究进展[J]. 上海交通大学学报(医学版), 2021, 41(9): 1261-1266.

Qian-long ZHANG, Ying TIAN. Progress in the influence of prenatal exposure to phthalates on placental function and its mechanism[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(9): 1261-1266.

图/表 1

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Country	Number	Gestational period	Metabolite of PAEs								Reference
Country	Number	Gestational period	MMP	MEP	MnBP	MiBP	MBzP	MDEHP	MCOP	Unit	Reference
China	3 103	≤14 weeks	11.99	11.99	47.27		0.08	13.9		µg·g^-1；median	［16］
China	210	≤12 weeks		8.30	19.72	11.59		40.09		ng·mL^-1；GM	［12］
China	210	13‒27weeks		6.09	27.77	10.69		43.93		ng·mL^-1；GM	［12］
China	210	28‒40 weeks		4.42	24.67	9.73		35.13		ng·mL^-1；GM	［12］
Japan	111	9‒40weeks	5.7	7.75	46.6		3.57	18.5		ng·mL^-1；median	［17］
America	446	20‒28 weeks	1.6	41.1	9.4	7.1	5.5	75.5	20.5	µg·g^-1；GM	［18］
America	378	18‒22 weeks	1.92	47.0	13.7	9.57	9.47	14.01		ng·mL^-1；median	［19］
America	50	≤12 weeks，22‒24 weeks	1.3	68.7	17.9	1.6	7.7	38.0		ng·mL^-1；median	［20］
America	596	Progestation		40.8	10.4	6.5	2.7	47.0		ng·mL^-1；median	［4］
America	132	6，21 and 35 weeks		37.7	10.2	6.3	2.5	36.1		ng·mL^-1；median	［4］
America	380	18‒22 weeks， 24‒32 weeks	2.2	46.7	16.3	10.8	11.9	92.8/（nmol·L^-1）		ng·mL^-1；median	［21］
America	168	≤13 weeks		30.37	6.04	3.46	2.98	65.58	15.40	ng·mL^-1；GM	［22］
America	168	14‒27 weeks		28.14	5.36	4.03	2.94	64.43	12.19	ng·mL^-1；GM	［22］
America	168	≥28 weeks		28.14	6.98	5.34	3.31	69.91/（nmol·L^-1）	13.32	ng·mL^-1；GM	［22］
America	753	≤13 weeks		28.4	6.36	3.97	3.31	71.7/（nmol·L^-1）	14.5	ng·mL^-1；GM	［23］
Canada	2 000	˂13 weeks	ND	28.00	12.00		5.20	18.1		ng·mL^-1；median	［24］
Canada	370	≤13 weeks	ND	25.00	12.00		5.40	57.50/（nmol·L^-1）		ng·mL^-1；median	［25］
Netherlands	100	≥20 weeks	ND	222.0	62.2	57.1	11.7	76.9		µg·g^-1；median	［26］
Norway	116	13‒27 weeks		55.0	25.0	20.0	11.0	66.0		ng·mL^-1；median	［27］
Spain	391	≤12 weeks		246.0	27.1	28.4	10.6	87.8		µg·g^-1；median	［28］
Spain	391	28‒40 weeks		386.0	28.1	29.8	10.0	80.0		µg·g^-1；median	［28］
France	473	23‒29 weeks		94.0	43.4	39.4	18.2	330.0/（nmol·L^-1）	3.86	ng·mL^-1；median	［5］
Greece	239	10‒13 weeks		132.6	33.2	38.7	7.0	47.6		µg·g^-1；median	［29］

Country	Number	Gestational period	Metabolite of PAEs								Reference
Country	Number	Gestational period	MMP	MEP	MnBP	MiBP	MBzP	MDEHP	MCOP	Unit	Reference
China	3 103	≤14 weeks	11.99	11.99	47.27		0.08	13.9		µg·g^-1；median	［16］
China	210	≤12 weeks		8.30	19.72	11.59		40.09		ng·mL^-1；GM	［12］
China	210	13‒27weeks		6.09	27.77	10.69		43.93		ng·mL^-1；GM	［12］
China	210	28‒40 weeks		4.42	24.67	9.73		35.13		ng·mL^-1；GM	［12］
Japan	111	9‒40weeks	5.7	7.75	46.6		3.57	18.5		ng·mL^-1；median	［17］
America	446	20‒28 weeks	1.6	41.1	9.4	7.1	5.5	75.5	20.5	µg·g^-1；GM	［18］
America	378	18‒22 weeks	1.92	47.0	13.7	9.57	9.47	14.01		ng·mL^-1；median	［19］
America	50	≤12 weeks，22‒24 weeks	1.3	68.7	17.9	1.6	7.7	38.0		ng·mL^-1；median	［20］
America	596	Progestation		40.8	10.4	6.5	2.7	47.0		ng·mL^-1；median	［4］
America	132	6，21 and 35 weeks		37.7	10.2	6.3	2.5	36.1		ng·mL^-1；median	［4］
America	380	18‒22 weeks， 24‒32 weeks	2.2	46.7	16.3	10.8	11.9	92.8/（nmol·L^-1）		ng·mL^-1；median	［21］
America	168	≤13 weeks		30.37	6.04	3.46	2.98	65.58	15.40	ng·mL^-1；GM	［22］
America	168	14‒27 weeks		28.14	5.36	4.03	2.94	64.43	12.19	ng·mL^-1；GM	［22］
America	168	≥28 weeks		28.14	6.98	5.34	3.31	69.91/（nmol·L^-1）	13.32	ng·mL^-1；GM	［22］
America	753	≤13 weeks		28.4	6.36	3.97	3.31	71.7/（nmol·L^-1）	14.5	ng·mL^-1；GM	［23］
Canada	2 000	˂13 weeks	ND	28.00	12.00		5.20	18.1		ng·mL^-1；median	［24］
Canada	370	≤13 weeks	ND	25.00	12.00		5.40	57.50/（nmol·L^-1）		ng·mL^-1；median	［25］
Netherlands	100	≥20 weeks	ND	222.0	62.2	57.1	11.7	76.9		µg·g^-1；median	［26］
Norway	116	13‒27 weeks		55.0	25.0	20.0	11.0	66.0		ng·mL^-1；median	［27］
Spain	391	≤12 weeks		246.0	27.1	28.4	10.6	87.8		µg·g^-1；median	［28］
Spain	391	28‒40 weeks		386.0	28.1	29.8	10.0	80.0		µg·g^-1；median	［28］
France	473	23‒29 weeks		94.0	43.4	39.4	18.2	330.0/（nmol·L^-1）	3.86	ng·mL^-1；median	［5］
Greece	239	10‒13 weeks		132.6	33.2	38.7	7.0	47.6		µg·g^-1；median	［29］

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