表1
不同孕期PM2.5暴露对母婴甲状腺功能影响的研究
Table1.Studies on effects of PM2.5 exposure on maternal and infant thyroid function across different gestational periods
2022, 39(12):1417-1422.doi:10.11836/JEOM22160
由于胎儿甲状腺激素在妊娠早期几乎完全依赖于母体，因此妊娠早期母体甲状腺功能与胎儿生长发育密切相关。有研究表明儿童神经功能缺陷，包括智力低下、认知迟缓和运动神经发育障碍是孕早期甲状腺功能减退引起的主要并发症[1-3]。虽然碘摄入不足是甲状腺功能不全的常见原因，但也有越来越多的研究结果表明大气污染是甲状腺功能障碍的重要影响因素之一。本综述将概述PM2.5暴露在妊娠期对母婴甲状腺功能产生的影响和不良后果。
甲状腺由甲状腺滤泡的上皮细胞组成，具有合成、储存和分泌甲状腺激素的功能。胎儿的生长发育与甲状腺激素密切相关，甲状腺功能对正常妊娠也至关重要。妊娠期作为女性的特殊时期，母体内分泌系统的分泌和代谢都会发生明显变化，甲状腺激素水平也发生一定改变，而母体甲状腺功能的细微变化都会对胎儿产生影响[4-5]。胎儿的甲状腺发育是从妊娠第6周开始的，在妊娠的前3个月里胎儿自身不能产生足够的甲状腺激素，从而高度依赖胎盘转移甲状腺素[6]。当母体四碘甲状腺原氨酸（thyroxine, T4）和三碘甲状腺原氨酸（triiodothyronine, T3）通过胎盘转移扩散后，胎儿甲状腺激素水平可以达到与成人相似的浓度范围，从而确保胎儿正常的生长发育[7]。
党晓平等[8]研究表示，孕期亚临床甲状腺功能减退会影响新生儿的甲状腺功能，且主要导致新生儿高促甲状腺激素血症的发生。Tapia-Martínez等[9]研究也发现，妊娠期和哺乳期母体甲状腺激素缺乏会导致子代甲状腺功能异常。荷兰的一项前瞻性队列研究结果表示，母体甲状腺激素水平与胎儿大脑灰质体积呈倒 “U” 形关系，胎儿大脑发育易受到母体甲状腺功能改变的影响，尤其在妊娠早期这种影响最为明显[10]。
甲状腺功能受下丘脑-垂体-甲状腺轴的调节，其稳态易受到环境污染物干扰。
妊娠前三个月，是胎儿对母体甲状腺功能障碍最敏感的时期。一项具有9931名孕妇的大型队列研究发现，在妊娠首月暴露于PM2.5会导致孕妇轻度甲状腺功能障碍，当孕妇妊娠前3个月均暴露在PM2.5环境中，其整个孕期的甲状腺功能都可能为异常状态，这可能提示暴露于 PM2.5会对婴⼉甲状腺激素稳态存在危害作⽤[11]。Zhou等[12]表示，孕早期PM2.5暴露与胎儿双顶径、头围、股骨长度和肱骨长度的大小具有关联，并且母体血清游离甲状腺素（free thyroxine, FT4）水平是PM2.5暴露与胎儿生长之间的中介。武汉的一项出生队列研究结果同样表明，孕前和孕早期母体PM2.5暴露与孕妇的FT4水平呈负相关，而FT4降低提示中枢性甲状腺功能的减退，可能会造成母体甲状腺功能障碍[13]。Qiu等[14]研究发现，孕早期PM2.5与金属混合暴露后会导致母体血清游离甲状腺素和血清游离三碘甲状腺素（serum free triiodothyronine, FT3）水平降低。武汉市一项出生队列研究发现，当母亲在妊娠前三个月暴露于PM2.5可能与妊娠第10—17周时母体较低的血清FT4浓度和FT4/FT3值有关，而FT4/FT3值作为人体将甲状腺素转化为三碘甲状腺原氨酸的有效指标，当其下降时提示母体可能正处于甲状腺功能减退的状态[15]。
孕中期作为胎儿开始在体内产生自己的T4的时间点，对于胎儿正在发育的甲状腺来说，这恰巧是胎儿甲状腺的敏感阶段。美国加州的一项调查发现，产前PM2.5暴露与新生儿血清总甲状腺素（total thyroxine, TT4）水平之间有关联，尤其在妊娠中期，而新生儿足跟血中较高的TT4浓度与儿童认知发育和神经发育有关，因此在胎儿阶段过高的甲状腺激素水平会对儿童正常生长产生一定有害影响[16]。Zhao等[17]的研究认为，在孕中期PM2.5暴露会引起母体FT4水平降低，这可能会增加母亲患低甲状腺素血症的风险，而母体低甲状腺素血症与子代神经发育缺陷之间存在因果关系，因此PM2.5暴露对子代发育的影响值得关注。妊娠中期作为PM2.5暴露的窗口期之一，该阶段PM2.5暴露对母婴甲状腺功能的影响更需重点关注，但目前国内外相关研究均较少。
比利时的ENVIRONAGE出生队列研究了孕晚期PM2.5暴露对胎儿和母体甲状腺激素的影响，表示妊娠晚期 PM2.5暴露与脐带血中的促甲状腺激素（thyroid stimulating hormone, TSH ）水平和FT4/FT3值呈负相关，通过中介分析得出脐带血FT4是孕晚期PM2.5暴露与胎儿出生体重之间关联的中介[18]。西班牙的一项调查结果显示，母亲在怀孕期间接触PM2.5与婴儿出生时的TT4水平呈正相关，在孕第31~37周关联性达到最强[19]。Ilias等[20]在希腊雅典开展的研究结果表示，孕晚期PM2.5 暴露与母体TSH之间存在剂量反应关系，在正常的甲状腺功能状态下这种关系更为明显，而过低的TSH会导致母体甲状腺激素释放不足。Neven等[21]研究发现，当孕晚期暴露于PM2.5与较低的胎盘碘浓度有关，这表示环境空气污染可能会干扰碘的正常摄取，导致胎儿神经发育不完善。Harari-Kremer等[22]发现当孕晚期暴露于PM2.5会提高新生儿患中枢性发热的风险，而患有短暂性中枢性发热的新生儿会出现暂时的甲状腺激素分泌不足。青岛的一项时间序列研究结果与Harari-Kremer等的发现具有相似性，结果表明，当孕产妇在产前两个月期间PM2.5暴露会增加新生儿患先天性甲状腺功能减退症的概率[23]。
不同孕期PM2.5暴露对母婴甲状腺功能影响的研究见表1。
不同孕期PM2.5暴露对母婴甲状腺功能影响的研究
Table1.Studies on effects of PM2.5 exposure on maternal and infant thyroid function across different gestational periods
有研究表明，PM2.5可以穿过胎盘屏障，进入胎儿体内。黑炭作为PM2.5的组分之一，有研究者表示在胎盘组织中发现了黑炭颗粒的存在，并且发现胎盘黑炭负荷量与孕期母亲黑炭暴露之间存在正相关，这可能是细颗粒物可以通过胎盘屏障转移到胎盘内的重要证据之一[26]。在动物模型实验和体外模型实验中也发现细颗粒物可以到达胎盘进入胎儿体内，对胎盘功能和后代健康都产生直接影响[27]。PM2.5对儿童造成的不良后果主要通过两种机制引起：①直接穿过胎盘，从而到达胎儿自身循环；②细颗粒物导致母体和胎盘组织发生氧化应激、炎症、DNA修饰等[28]。Yue等[29]研究显示，妊娠期暴露于PM2.5会导致胎盘的组织病理学变化和血管损伤，PM2.5暴露会降低母体血窦和胎儿血管的平均面积，并抑制CD31蛋白表达。一项动物实验表示，当孕期小鼠暴露于PM2.5，首先会诱导母体肺部炎症，然后引起全身和胎盘炎症，并破坏胎盘血管生成影响胎儿的正常生长[30]。Lu等[31]的动物实验也表明，健康小鼠妊娠期间暴露于PM2.5污染后，可在胎盘组织中检测到炎症指标白细胞介素-4的增高。一项坦桑尼亚的前瞻性研究报道，当妊娠期PM2.5暴露水平较高时，胎盘会出现炎症性病变，增高胎儿患血栓的可能[32]。妊娠期PM2.5暴露也可通过影响DNA修饰引发部分胎盘病理改变。Maghbooli等[33]研究发现，在妊娠前3个月PM2.5与胎盘DNA甲基化水平改变相关，而DNA甲基化模式等改变可以调节免疫反应和炎症基因抑制胎盘功能。美国的一项出生队列研究显示，孕妇在怀孕期间接触PM2.5会改变胎盘脂质和葡萄糖代谢相关基因表达，这可能表明妊娠期PM2.5暴露会改变胎盘代谢功能影响胎儿生长和胎儿产后发育[34]。
与尿碘相比，使用胎盘碘浓度作为长期妊娠积累标志更为可靠和准确，它受饮食波动影响较小，可以保护胎儿免受母体碘摄入暂时不足的影响，并且胎盘碘可能是观察新生儿甲状腺激素水平的较好指标[35-36]。比利时ENVIRONAGE出生队列研究显示，妊娠晚期PM2.5暴露与胎盘碘负荷较低有关，其中胎盘碘可能会对新生儿甲状腺激素水平产生影响[37]。Neven等[21]研究也表示，孕晚期PM2.5暴露与胎盘碘浓度之间存在负相关，这种下降表明环境大气污染可能会干扰胎盘对碘的正常摄取。在碘缺乏状态下，机体会增加对PM2.5暴露的敏感性，PM2.5及其附着的⽔溶性阴离⼦暴露可作为碘摄取抑制剂影响甲状腺功能[38]。因此了解孕期PM2.5暴露与胎盘碘摄取、母婴甲状腺功能间的关系，对于预防孕妇的不良妊娠结局和胎⼉的神经⽣长发育具有重要的意义。
母亲甲状腺功能异常与围生期并发症风险增加有关，包括早产、低出生体重、胎盘早剥、先兆子痫以及胎儿神经发育异常等[39-40]。由于甲状腺功能极易受到环境干扰，有证据表明孕期是PM2.5污染影响胎儿生长发育的重要窗口期[41-42]。孕早期母体甲状腺激素升高对胎儿神经发育起到关键作用。Li等[13]研究表示，孕早期PM2.5暴露和24个月大的子代神经发育状况具有相关性，母体甲状腺激素在孕前PM2.5暴露与子代神经发育之间起到中介作用。出生体重作为反映宫内环境的重要指标，也是新生儿发病率和死亡率的重要预测指标。Janssen等[18]研究指出，孕前和孕早期是母亲PM2.5暴露对胎儿生长受限的易感关键窗口期，并表示由于PM2.5暴露可能会破坏胎盘在生长激素和脂肪酸调节方面的作用，从而导致胎儿出生体重较轻。此外，一项在上海市开展回顾性队列研究表示，孕中期母亲暴露于大气污染物可能会导致新生儿出生体重降低[43]。上海-闵行出生队列的研究表示，产前暴露PM2.5及其主要化学成分与儿童1~6岁时身高（身长）别体重Z评分和年龄别体重比值降低相关[44]。一项动物实验研究结果发现，孕鼠产前暴露PM2.5会导致子代小鼠出现焦虑行为和血清FT3水平增高，此结果可能与子代小鼠甲状腺激素通路相关基因的改变有关[45]。Wang等[46]研究表示PM2.5中的有机物、黑炭、硫酸盐、硝酸盐可能是导致新生儿低出生体重的主要物质，当孕晚期暴露于PM2.5及其成分与孕产妇 FT4 水平之间存在负相关，母体FT4在PM2.5暴露和新生儿低出生体重之间起到中介作用。因此，进一步研究PM2.5暴露的危害对保护子代健康也起到重要作用。
孕期暴露于PM2.5污染孕产妇子代表现出体重较轻、神经行为能力减弱等不良妊娠结局可能与氧化应激、炎症或DNA修饰有关。有研究发现孕早期自然流产的孕妇的血清TSH和血清丙二醛水平较高，并且血清TSH与超氧化物歧化酶水平呈负相关，母体甲状腺障碍导致氧化应激增强和抗氧化防御能力丧失是妊娠中止的原因之一[47]。产前和产后早期PM2.5暴露与儿童自闭症谱系障碍发病率之间存在关联，PM2.5可以诱导母体发生炎症反应，增加促炎细胞因子，这些促炎细胞因子可以直接穿过胎盘到达胚胎，对胎儿产生不良影响[48]。Zeng等[49]表示，BAI1基因甲基化可能在孕期母体暴露于PM2.5污染导致子代大脑发育异常中起到中介作用。Zhang等[50]研究表示，妊娠期与哺乳期小鼠PM2.5暴露会导致子代的空间学习和记忆受损，这可能与母体氧化应激、炎症反应和CREB/BDNF信号通路的调节有关。一项动物实验研究表明，小鼠孕期PM2.5暴露后，其胎盘细胞的增殖能力会受到抑制，并改变胎盘中的营养转运蛋白表达，导致胎儿营养供应中断影响胎儿正常发育[51]。Kingsley等[52]报道称，住所靠近道路主干道受PM2.5污染较为严重的孕妇，其子代低出生体重与胎盘LINE-1甲基化较低之间具有相关性。有研究显示PM2.5暴露会导致小鼠甲状腺的组织学改变和甲状腺功能障碍发生，PM2.5暴露通过Rap1/PI3K/AKT通路激活GLIS3，以促进与甲状腺激素合成相关蛋白的表达[53]。
毋庸置疑，细颗粒物空气污染无处不在，PM2.5暴露导致的甲状腺功能改变已成为国内外研究重点，早期甲状腺功能改变会对健康产生长期影响，进一步了解细颗粒物对妊娠期妇女、胎儿及新生儿健康造成的影响存在其特有价值和重要性。新疆地处中国西北边陲，亚欧大陆腹部，远离海洋，外环境碘资源较为匮乏，碘缺乏病一直是防治的重点。并且新疆气候干旱，当秋冬季发生沙尘天气时，大气质量较差，针对当地妊娠期妇女这一特殊群体，关注PM2.5污染暴露与甲状腺疾病关联性也显得尤为重要，控制PM2.5污染和宣传其暴露危害性已迫在眉睫，这将有助于减少由细颗粒物暴露引起的妊娠期疾病，并对胎儿和新生儿健康成长起到一定保护作用。
表1 不同孕期PM2.5暴露对母婴甲状腺功能影响的研究
Table 1Studies on effects of PM2.5 exposure on maternal and infant thyroid function across different gestational periods
| [1] |
PREZIOSO G, GIANNINI C, CHIARELLI F. Effect of thyroid hormones on neurons and neurodevelopment[J]. Horm Res Paediatr, 2018, 90(2): 73-81. DOI: 10.1159/000492129 |
| [2] |
MAHADIK K, CHOUDHARY P, ROY P K. Study of thyroid function in pregnancy, its feto-maternal outcome; a prospective observational study[J]. BMC Pregnancy Childbirth, 2020, 20(1): 769. DOI: 10.1186/s12884-020-03448-z |
| [3] |
GUO J L, WU M, GAO X, et al. Meconium exposure to phthalates, sex and thyroid hormones, birth size and pregnancy outcomes in 251 Mother–Infant Pairs from Shanghai[J]. Int J Environ Res Public Health, 2020, 17(21): 7711. DOI: 10.3390/ijerph17217711 |
| [4] |
ZHANG C, YANG X, ZHANG Y, et al. Association between maternal thyroid hormones and birth weight at early and late pregnancy[J]. J Clin Endocrinol Metab, 2019, 104(12): 5853-5863. DOI: 10.1210/jc.2019-00390 |
| [5] |
MOLETI M, DI MAURO M, STURNIOLO G, et al. Hyperthyroidism in the pregnant woman: Maternal and fetal aspects[J]. J Clin Transl Endocrinol, 2019, 16: 100190. |
| [6] |
YANG X, YU Y, ZHANG C, et al. The association between isolated maternal hypothyroxinemia in early pregnancy and preterm birth[J]. Thyroid, 2020, 30(12): 1724-1731. DOI: 10.1089/thy.2019.0818 |
| [7] |
VERHAGEN N J E, GOWACHIRAPANT S, WINICHAGOON P, et al. Iodine supplementation in mildly iodine-deficient pregnant women does not improve maternal thyroid function or child development: A secondary analysis of a randomized controlled trial[J]. Front Endocrinol (Lausanne), 2020, 11: 572984. DOI: 10.3389/fendo.2020.572984 |
| [8] |
党晓平, 胡小剑, 贾毅, 等. 妊娠合并亚临床甲状腺功能减退症TSH值对新生儿甲功的影响[J]. 延安大学学报(医学科学版), 2020, 18(4): 51-54. DANG X P, HU X J, JIA Y, et al. Correlation analysis between maternal subclinical hypothyroidism and neonatal abnormal thyroid function and the effect of TSH on neonatal thyroid function[J]. J Yan'an Univ (Med Sci Ed), 2020, 18(4): 51-54. |
| [9] |
TAPIA-MARTÍNEZ J, TORRES-MANZO A P, FRANCO-COLÍN M, et al. Maternal thyroid hormone deficiency during gestation and lactation alters metabolic and thyroid programming of the offspring in the adult stage[J]. Horm Metab Res, 2019, 51(6): 381-388. DOI: 10.1055/a-0896-0968 |
| [10] |
JANSEN T A, KOREVAAR T I M, MULDER T A, et al. Maternal thyroid function during pregnancy and child brain morphology: A time window-specific analysis of a prospective cohort[J]. Lancet Diabetes Endocrinol, 2019, 7(8): 629-637. DOI: 10.1016/S2213-8587(19)30153-6 |
| [11] |
GHASSABIAN A, PIEROTTI L, BASTERRECHEA M, et al. Association of exposure to ambient air pollution with thyroid function during pregnancy[J]. JAMA Netw Open, 2019, 2(10): e1912902-e1912902. DOI: 10.1001/jamanetworkopen.2019.12902 |
| [12] |
ZHOU Y, ZHU Q, WANG P, et al. Early pregnancy PM2.5 exposure and its inorganic constituents affect fetal growth by interrupting maternal thyroid function[J]. Environ Pollut, 2022, 307: 119481. DOI: 10.1016/j.envpol.2022.119481 |
| [13] |
LI J, LIAO J, HU C, et al. Preconceptional and the first trimester exposure to PM2.5 and offspring neurodevelopment at 24 months of age: Examining mediation by maternal thyroid hormones in a birth cohort study[J]. Environ Pollut, 2021, 284: 117133. DOI: 10.1016/j.envpol.2021.117133 |
| [14] |
QIU L, SHEN W, YE C, et al. Association of exposure to PM2.5-bound metals with maternal thyroid function in early pregnancy[J]. Sci Total Environ, 2022, 810: 151167. DOI: 10.1016/j.scitotenv.2021.151167 |
| [15] |
ZHANG X, HUELS A, MAKUCH R, et al. Association of exposure to ambient particulate matter with maternal thyroid function in early pregnancy[J]. Environ Res, 2022, 214: 113942. DOI: 10.1016/j.envres.2022.113942 |
| [16] |
HOWE C G, ECKEL S P, HABRE R, et al. Association of prenatal exposure to ambient and traffic-related air pollution with newborn thyroid function: Findings from the children’s health study[J]. JAMA Netw Open, 2018, 1(5): e182172. DOI: 10.1001/jamanetworkopen.2018.2172 |
| [17] |
ZHAO Y, CAO Z, LI H, et al. Air pollution exposure in association with maternal thyroid function during early pregnancy[J]. J Hazard Mater, 2019, 367: 188-193. DOI: 10.1016/j.jhazmat.2018.12.078 |
| [18] |
JANSSEN B G, SAENEN N D, ROELS H A, et al. Fetal thyroid function, birth weight, and in utero exposure to fine particle air pollution: A birth cohort study[J]. Environ Health Perspect, 2017, 125(4): 699-705. DOI: 10.1289/EHP508 |
| [19] |
IRIZAR A, TXINTXURRETA A, MOLINUEVO A, et al. Association between prenatal exposure to air pollutants and newborn thyroxine (T4) levels[J]. Environ Res, 2021, 197: 111132. DOI: 10.1016/j.envres.2021.111132 |
| [20] |
ILIAS I, KAKOULIDIS I, TOGIAS S, et al. Atmospheric pollution and thyroid function of pregnant women in Athens, Greece: A pilot study[J]. Med Sci (Basel), 2020, 8(2): 19. |
| [21] |
NEVEN K, COX B, GYSELAERS W, et al. Host and environmental determinants of placental iodine concentrations[J]. Environ Epidemiol, 2019, 3: 286. |
| [22] |
HARARI-KREMER R, CALDERON-MARGALIT R, KOREVAAR T I M, et al. Associations between prenatal exposure to air pollution and congenital hypothyroidism[J]. Am J Epidemiol, 2021, 190(12): 2630-2638. DOI: 10.1093/aje/kwab187 |
| [23] |
PAN S, NI W, LI W, et al. Effects of PM2.5 and PM10 on congenital hypothyroidism in Qingdao, China, 2014-2017: A quantitative analysis[J]. Ther Adv Endocrinol Metab, 2019: 10. DOI: 10.1177/2042018819892151 |
| [24] |
KOREVAAR T I M, CHAKER L, JADDOE V W V, et al. Maternal and birth characteristics are determinants of offspring thyroid function[J]. J Clin Endocrinol Metab, 2016, 101(1): 206-213. DOI: 10.1210/jc.2015-3559 |
| [25] |
NEVEN K Y, MARIEN C B D, JANSSEN B G, et al. Variability of iodine concentrations in the human placenta[J]. Sci Rep, 2020, 10(1): 161. DOI: 10.1038/s41598-019-56775-3 |
| [26] |
BOVÉ H, BONGAERTS E, SLENDERS E, et al. Ambient black carbon particles reach the fetal side of human placenta[J]. Nat Commun, 2019, 10(1): 3866. DOI: 10.1038/s41467-019-11654-3 |
| [27] |
BONGAERTS E, NAWROT T S, VAN PEE T, et al. Translocation of (ultra)fine particles and nanoparticles across the placenta; a systematic review on the evidence of in vitro, ex vivo, and in vivo studies[J]. Part Fibre Toxicol, 2020, 17(1): 56. DOI: 10.1186/s12989-020-00386-8 |
| [28] |
BEHLEN J C, LAU C H, LI Y, et al. Gestational exposure to ultrafine particles reveals sex-and dose-specific changes in offspring birth outcomes, placental morphology, and gene networks[J]. Toxicol Sci, 2021, 184(2): 204-213. DOI: 10.1093/toxsci/kfab118 |
| [29] |
YUE H, JI X, ZHANG Y, et al. Gestational exposure to PM2.5 impairs vascularization of the placenta[J]. Sci Total Environ, 2019, 665: 153-161. DOI: 10.1016/j.scitotenv.2019.02.101 |
| [30] |
TAO S, ZHANG X, TIAN F, et al. Maternal exposure to ambient PM2.5 causes fetal growth restriction via the inhibition of spiral artery remodeling in mice[J]. Ecotoxicol Environ Saf, 2022, 237: 113512. DOI: 10.1016/j.ecoenv.2022.113512 |
| [31] |
LU X, FU H, HAN F, et al. Lipoxin A4 regulates PM2.5-induced severe allergic asthma in mice via the Th1/Th2 balance of group 2 innate lymphoid cells[J]. J Thorac Dis, 2018, 10(3): 1449-1459. DOI: 10.21037/jtd.2018.03.02 |
| [32] |
WYLIE B J, MATECHI E, KISHASHU Y, et al. Placental pathology associated with household air pollution in a cohort of pregnant women from dar es salaam, tanzania[J]. Environ Health Perspect, 2017, 125(1): 134-140. DOI: 10.1289/EHP256 |
| [33] |
MAGHBOOLI Z, HOSSEIN-NEZHAD A, ADABI E, et al. Air pollution during pregnancy and placental adaptation in the levels of global DNA methylation[J]. PLoS One, 2018, 13(7): e0199772. DOI: 10.1371/journal.pone.0199772 |
| [34] |
KAUR K, LESSEUR C, DEYSSENROTH M A, et al. PM2.5 exposure during pregnancy is associated with altered placental expression of lipid metabolic genes in a US birth cohort[J]. Environ Res, 2022, 211: 113066. DOI: 10.1016/j.envres.2022.113066 |
| [35] |
NEVEN K Y, COX B, VRIJENS K, et al. Determinants of placental iodine concentrations in a mild-to-moderate iodine-deficient population: An ENVIRONAGE cohort study[J]. J Transl Med, 2020, 18(1): 426. DOI: 10.1186/s12967-020-02601-8 |
| [36] |
KARAOGLAN M, İŞBILEN E. The role of placental iodine storage in the neonatal thyroid stimulating hormone surge: Iodine as a driving force to adapt the terrestrial life[J]. J Endocrinol Invest, 2021, 44(5): 1041-1052. DOI: 10.1007/s40618-020-01399-y |
| [37] |
NEVEN K Y, WANG C, JANSSEN B G, et al. Ambient air pollution exposure during the late gestational period is linked with lower placental iodine load in a belgian birth cohort[J]. Environ Int, 2021, 147: 106334. DOI: 10.1016/j.envint.2020.106334 |
| [38] |
MILLER C N, RAYALAM S. The role of micronutrients in the response to ambient air pollutants: Potential mechanisms and suggestions for research design[J]. J Toxicol Environ Health B Crit Rev, 2017, 20(1): 38-53. DOI: 10.1080/10937404.2016.1261746 |
| [39] |
MARTÍNEZ M, SOLDEVILA B, LUCAS A, et al. Hypothyroidism during pregnancy and its association to perinatal and obstetric morbidity: A review[J]. Endocrinol Diabetes Nutr (Engl Ed), 2018, 65(2): 107-113. |
| [40] |
MARAKA S, OSPINA N M S, O'KEEFFE D T, et al. Subclinical hypothyroidism in pregnancy: A systematic review and meta-analysis[J]. Thyroid, 2016, 26(4): 580-590. DOI: 10.1089/thy.2015.0418 |
| [41] |
LIU N M, MIYASHITA L, MAHER B A, et al. Evidence for the presence of air pollution nanoparticles in placental tissue cells[J]. Sci Total Environ, 2021, 751: 142235. DOI: 10.1016/j.scitotenv.2020.142235 |
| [42] |
GHAZI T, NAIDOO P, NAIDOO R N, et al. Prenatal air pollution exposure and placental DNA methylation changes: Implications on fetal development and future disease susceptibility[J]. Cells, 2021, 10(11): 3025. DOI: 10.3390/cells10113025 |
| [43] |
蔡任之, 钱耐思, 虞慧婷, 等. 母亲孕中期空气污染暴露与新生儿出生体重的相关性[J]. 环境与职业医学, 2017, 34(6): 479-482. DOI: 10.13213/j.cnki.jeom.2017.16800CAI R Z, QIAN N S, YU H T, et al. Association between maternal air pollution in second trimester and birth weight[J]. J Environ Occup Med, 2017, 34(6): 479-482. DOI: 10.13213/j.cnki.jeom.2017.16800 |
| [44] |
SUN X, LIU C, LIANG H, et al. Prenatal exposure to residential PM2.5 and its chemical constituents and weight in preschool children: A longitudinal study from Shanghai, China[J]. Environ Int, 2021, 154: 106580. DOI: 10.1016/j.envint.2021.106580 |
| [45] |
LI S, LIU Y, LIU B, et al. Maternal urban particulate matter exposure and signaling pathways in fetal brains and neurobehavioral development in offspring[J]. Toxicology, 2022, 474: 153225. DOI: 10.1016/j.tox.2022.153225 |
| [46] |
WANG X, LIU C, ZHANG M, et al. Evaluation of maternal exposure to PM2.5 and its components on maternal and neonatal thyroid function and birth weight: A cohort study[J]. Thyroid, 2019, 29(8): 1147-1157. DOI: 10.1089/thy.2018.0780 |
| [47] |
RAMANDEEP K, KAPIL G, HARKIRAN K. Correlation of enhanced oxidative stress with altered thyroid profile: Probable role in spontaneous abortion[J]. Int J Appl Basic Med Res, 2017, 7(1): 20-25. DOI: 10.4103/2229-516X.198514 |
| [48] |
AHADULLAH, YAU S Y, LU H X, et al. PM2.5 as a potential risk factor for autism spectrum disorder: Its possible link to neuroinflammation, oxidative stress and changes in gene expression[J]. Neurosci Biobehav Rev, 2021, 128: 534-548. DOI: 10.1016/j.neubiorev.2021.06.043 |
| [49] |
ZENG Z, XU X, WANG Q, et al. Maternal exposure to atmospheric PM2.5 and fetal brain development: Associations with BAI1 methylation and thyroid hormones[J]. Environ Pollut, 2022, 308: 119665. DOI: 10.1016/j.envpol.2022.119665 |
| [50] |
ZHANG M, LIU W, ZHOU Y, et al. Neurodevelopmental toxicity induced by maternal PM2.5 exposure and protective effects of quercetin and vitamin C[J]. Chemosphere, 2018, 213: 182-196. DOI: 10.1016/j.chemosphere.2018.09.009 |
| [51] |
ZHU N, JI X, GENG X, et al. Maternal PM2.5 exposure and abnormal placental nutrient transport[J]. Ecotoxicol Environ Saf, 2021, 207: 111281. DOI: 10.1016/j.ecoenv.2020.111281 |
| [52] |
KINGSLEY S L, ELIOT M N, WHITSEL E A, et al. Maternal residential proximity to major roadways, birth weight, and placental DNA methylation[J]. Environ Int, 2016, 92-93: 43-49. DOI: 10.1016/j.envint.2016.03.020 |
| [53] |
TANG S, LI D, DING H, et al. GLIS3 mediated by the Rap1/PI3K/AKT signal pathway facilitates real-ambient PM2.5 exposure disturbed thyroid hormone homeostasis regulation[J]. Ecotoxicol Environ Saf, 2022, 232: 113248. DOI: 10.1016/j.ecoenv.2022.113248 |
[基金项目] 国家自然科学基金地区科学基金项目（82160650，82260648）
[作者简介]
[收稿日期] 2022-05-10
引用格式
周婧,
张玲,
王琛琛, 等.
孕期PM2.5暴露致母婴甲状腺功能影响的研究进展
[J].环境与职业医学,
2022, 39(12): 1417-1422.
doi:10.11836/JEOM22160.
ZHOU Jing , ZHANG Ling , WANG Chenchen , WU Shunhua . Research progress on effects of PM2.5 exposure during pregnancy on maternal and infant thyroid function .Journal of Environmental & Occupational Medicine, 2022, 39(12): 1417-1422. doi:10.11836/JEOM22160.