环境重金属暴露与子宫内膜异位症

doi:10.12280/gjszjk.20210136

摘要/Abstract

摘要：

子宫内膜异位症（EMs）发生发展机制包括内分泌、遗传、免疫和环境因素。环境污染会导致水源、土壤以及空气中积累大量重金属,如铁、镍和镉等元素。妇女暴露于这些重金属,大量重金属进入体内,在其体内与某些有机成分结合形成金属络合物或金属整合物,后者促进活性氧（ROS）的产生。ROS通过激活丝裂原活化蛋白激酶（MAPK）途径,加重机体氧化应激,进而促进内膜细胞的增殖和对异位病灶的侵袭。部分重金属如镉、镍等,在体内能与雌激素受体（ER）特异性结合,产生类雌激素效应,干扰内分泌代谢,增加女性罹患EMs的风险。综述妇女暴露于环境重金属与EMs的相关性及研究进展,为探讨EMs发生发展机制积累新的资料。

关键词: 金属,重, 子宫内膜异位症, 环境污染, 氧化性应激, 铁, 镍, 镉

Abstract:

The etiological and pathophysiological mechanisms of endometriosis (EMs) include endocrine, genetic, immune and environmental factors. Environmental pollution can lead to the accumulation of a large number of heavy metal elements, such as iron, nickel and cadmium, in water, soil and air. If women were exposed to this kind of environment, a lot of these heavy metals could enter into their bodies. After that, these heavy metals were combined with some organic compounds in body to form the metallic integration or metal-protein complex that promote the production of harmful reactive oxygen species (ROS). Many studies have showed that ROS promotes the proliferation of endometrial cells and the invasion of ectopic lesions by activating the mitogen-activated protein kinase (MAPK) pathway and aggravating oxidative stress. Some heavy metals, such as cadmium and nickel, can specifically bind with estrogen receptor (ER) in the body, by which the estrogen-like effects were induced so as to interfere with endocrine and metabolism, and to increase the risk of EMs in women. This paper reviews the correlation between the environmental heavy metal exposure and the pathophysiological mechanism of EMs, as well as the research progress, as to add a new reference for us to explore the etiology and pathophysiology of EMs.

Key words: Metals, heavy, Endometriosis, Environmental pollution, Oxidative stress, Iron, Nickel, Cadmium

沈凌超, 纪冬梅. 环境重金属暴露与子宫内膜异位症[J]. 国际生殖健康/计划生育, 2021, 40(6): 504-508.

SHEN Ling-chao, JI Dong-mei. Environmental Heavy Metal Exposure and Endometriosis[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(6): 504-508.

参考文献 42

[1]	郎景和. 对子宫内膜异位症认识的历史、现状与发展[J]. 中国实用妇科与产科杂志, 2020, 36(3):193-196. doi: 10.19538/j.fk2020030101. doi: 10.19538/j.fk2020030101
[2]	Lin YH, Chen YH, Chang HY, et al. Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies[J]. Int J Mol Sci, 2018, 19(8):2385. doi: 10.3390/ijms19082385. doi: 10.3390/ijms19082385 URL
[3]	Caporossi L, Capanna S, Viganò P, et al. From Environmental to Possible Occupational Exposure to Risk Factors: What Role Do They Play in the Etiology of Endometriosis?[J]. Int J Environ Res Public Health, 2021, 18(2):532. doi: 10.3390/ijerph18020532. doi: 10.3390/ijerph18020532 URL
[4]	Rehman K, Fatima F, Waheed I, et al. Prevalence of exposure of heavy metals and their impact on health consequences[J]. J Cell Biochem, 2018, 119(1):157-184. doi: 10.1002/jcb.26234. doi: 10.1002/jcb.26234 URL
[5]	Tytła M. Assessment of Heavy Metal Pollution and Potential Ecological Risk in Sewage Sludge from Municipal Wastewater Treatment Plant Located in the Most Industrialized Region in Poland-Case Study[J]. Int J Environ Res Public Health, 2019, 16(13):2430. doi: 10.3390/ijerph16132430. doi: 10.3390/ijerph16132430 URL
[6]	Ghorbani MR, Ghanavati N, Babaenejad T, et al. Assessment of the potential ecological and human health risks of heavy metals in Ahvaz oil field, Iran[J]. PLoS One, 2020, 15(11):e0242703. doi: 10.1371/journal.pone.0242703. doi: 10.1371/journal.pone.0242703 URL
[7]	Kumar S, Sharma A. Cadmium toxicity: effects on human reproduction and fertility[J]. Rev Environ Health, 2019, 34(4):327-338. doi: 10.1515/reveh-2019-0016. doi: 10.1515/reveh-2019-0016 URL
[8]	Mwilola PN, Mukumbuta I, Shitumbanuma V, et al. Lead, Zinc and Cadmium Accumulation, and Associated Health Risks, in Maize Grown near the Kabwe Mine in Zambia in Response to Organic and Inorganic Soil Amendments[J]. Int J Environ Res Public Health, 2020, 17(23):9038. doi: 10.3390/ijerph17239038. doi: 10.3390/ijerph17239038 URL
[9]	Bloom MS, Fujimoto VY, Steuerwald AJ, et al. Background exposure to toxic metals in women adversely influences pregnancy during in vitro fertilization (IVF)[J]. Reprod Toxicol, 2012, 34(3):471-481. doi: 10.1016/j.reprotox.2012.06.002. doi: 10.1016/j.reprotox.2012.06.002 URL
[10]	Thézénas ML, De Leo B, Laux-Biehlmann A, et al. Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions[J]. Sci Rep, 2020, 10(1):1495. doi: 10.1038/s41598-020-58362-3. doi: 10.1038/s41598-020-58362-3 URL
[11]	Kobayashi H, Yamada Y, Kawahara N, et al. Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis[J]. Oncol Rep, 2019, 41(3):1729-1738. doi: 10.3892/or.2018.6946. doi: 10.3892/or.2018.6946 pmid: 30592289
[12]	Członkowska A, Litwin T, Dusek P, et al. Wilson disease[J]. Nat Rev Dis Primers, 2018, 4(1):21. doi: 10.1038/s41572-018-0018-3. doi: 10.1038/s41572-018-0018-3 pmid: 30190489
[13]	Hao Y, Pang Y, Yan H, et al. Association of maternal serum copper during early pregnancy with the risk of spontaneous preterm birth: A nested case-control study in China[J]. Environ Int, 2019, 122:237-243. doi: 10.1016/j.envint.2018.11.009. doi: 10.1016/j.envint.2018.11.009 URL
[14]	Arumugam K. Endometriosis and infertility: raised iron concentration in the peritoneal fluid and its effect on the acrosome reaction[J]. Hum Reprod, 1994, 9(6):1153-1157. doi: 10.1093/oxfordjournals.humrep.a138649. doi: 10.1093/oxfordjournals.humrep.a138649 pmid: 7962392
[15]	Van Langendonckt A, Casanas-Roux F, Eggermont J, et al. Characterization of iron deposition in endometriotic lesions induced in the nude mouse model[J]. Hum Reprod, 2004, 19(6):1265-1271. doi: 10.1093/humrep/deh182. doi: 10.1093/humrep/deh182 pmid: 15105391
[16]	Mori M, Ito F, Shi L, et al. Ovarian endometriosis-associated stromal cells reveal persistently high affinity for iron[J]. Redox Biol, 2015, 6:578-586. doi: 10.1016/j.redox.2015.10.001. doi: 10.1016/j.redox.2015.10.001 URL
[17]	Kajiyama H, Suzuki S, Yoshihara M, et al. Endometriosis and cancer[J]. Free Radic Biol Med, 2019, 133:186-192. doi: 10.1016/j.freeradbiomed.2018.12.015. doi: 10.1016/j.freeradbiomed.2018.12.015 URL
[18]	和儒林, 刘玉环. 活性氧簇、氧化应激与子宫内膜异位症的关系研究进展[J]. 中华妇产科杂志, 2019, 54(3):206-209. doi: 10.3760/cma.j.issn.0529-567x.2019.03.015. doi: 10.3760/cma.j.issn.0529-567x.2019.03.015
[19]	Vallée A, Lecarpentier Y. Curcumin and Endometriosis[J]. Int J Mol Sci, 2020, 21(7):2440. doi: 10.3390/ijms21072440. doi: 10.3390/ijms21072440 URL
[20]	Polak G, Barczyński B, Wertel I, et al. Disrupted iron metabolism in peritoneal fluid may induce oxidative stress in the peritoneal cavity of women with endometriosis[J]. Ann Agric Environ Med, 2018, 25(4):587-592. doi: 10.26444/aaem/75802. doi: 10.26444/aaem/75802 URL
[21]	Hsu AL, Townsend PM, Oehninger S, et al. Endometriosis may be associated with mitochondrial dysfunction in cumulus cells from subjects undergoing in vitro fertilization-intracytoplasmic sperm injection, as reflected by decreased adenosine triphosphate production[J]. Fertil Steril, 2015, 103(2):347-352.e1. doi: 10.1016/j.fertnstert.2014.11.002. doi: 10.1016/j.fertnstert.2014.11.002 URL
[22]	Sreerangaraja Urs DB, Wu WH, Komrskova K, et al. Mitochondrial Function in Modulating Human Granulosa Cell Steroidogenesis and Female Fertility[J]. Int J Mol Sci, 2020, 21(10):3592. doi: 10.3390/ijms21103592. doi: 10.3390/ijms21103592 URL
[23]	Atkins HM, Bharadwaj MS, O′Brien Cox A, et al. Endometrium and endometriosis tissue mitochondrial energy metabolism in a nonhuman primate model[J]. Reprod Biol Endocrinol, 2019, 17(1):70. doi: 10.1186/s12958-019-0513-8. doi: 10.1186/s12958-019-0513-8 URL
[24]	Atkins HM, Appt SE, Taylor RN, et al. Systemic Iron Deficiency in a Nonhuman Primate Model of Endometriosis[J]. Comp Med, 2018, 68(4):298-307. doi: 10.30802/AALAS-CM-17-000082. doi: 10.30802/AALAS-CM-17-000082 URL
[25]	Burgovа EN, Khristidis YI, Kurkov AV, et al. The Inhibiting Effect of Dinitrosyl Iron Complexes with Thiol-containing Ligands on the Growth of Endometrioid Tumours in Rats with Experimental Endometriosis[J]. Cell Biochem Biophys, 2019, 77(1):69-77. doi: 10.1007/s12013-019-00865-6. doi: 10.1007/s12013-019-00865-6 URL
[26]	Silva N, Senanayake H, Waduge V. Elevated levels of whole blood nickel in a group of Sri Lankan women with endometriosis: a case control study[J]. BMC Res Notes, 2013, 6:13. doi: 10.1186/1756-0500-6-13. doi: 10.1186/1756-0500-6-13 URL
[27]	Yuk JS, Kim YJ, Yi KW, et al. High rate of nickel allergy in women with endometriosis: a 3-year population-based study[J]. J Obstet Gynaecol Res, 2015, 41(8):1255-1259. doi: 10.1111/jog.12707. doi: 10.1111/jog.12707 URL
[28]	Borghini R, Porpora MG, Casale R, et al. Irritable Bowel Syndrome-Like Disorders in Endometriosis: Prevalence of Nickel Sensitivity and Effects of a Low-Nickel Diet. An Open-Label Pilot Study[J]. Nutrients, 2020, 12(2):341. doi: 10.3390/nu12020341. doi: 10.3390/nu12020341 URL
[29]	Anderson G. Endometriosis Pathoetiology and Pathophysiology: Roles of Vitamin A, Estrogen, Immunity, Adipocytes, Gut Microbiome and Melatonergic Pathway on Mitochondria Regulation[J]. Biomol Concepts, 2019, 10(1):133-149. doi: 10.1515/bmc-2019-0017. doi: 10.1515/bmc-2019-0017 pmid: 31339848
[30]	Yuk JS, Shin JS, Shin JY, et al. Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based Nested Case-Control Study[J]. PLoS One, 2015, 10(10):e0139388. doi: 10.1371/journal.pone.0139388. doi: 10.1371/journal.pone.0139388 URL
[31]	Babaahmadifooladi M, Jacxsens L, Van de Wiele T, et al. Assessment of bioaccessible and dialyzable fractions of nickel in food products and their impact on the chronic exposure of Belgian population to nickel[J]. Food Chem, 2021, 342:128210. doi: 10.1016/j.foodchem.2020.128210. doi: 10.1016/j.foodchem.2020.128210 URL
[32]	Razumova Z, Govorov I, Östensson E, et al. Cadmium Intake as a Prognostic Factor in Endometrial Cancer: A Swedish Cohort-Based Study[J]. Nutr Cancer, 2021 Feb 17:1-9. Epub ahead of print. doi: 10.1080/01635581.2021.1883681. doi: 10.1080/01635581.2021.1883681
[33]	Prichystalova R, Caron-Beaudoin E, Richardson L, et al. An approach to classifying occupational exposures to endocrine disrupting chemicals by sex hormone function using an expert judgment process[J]. J Expo Sci Environ Epidemiol, 2021, 31(4):753-768. doi: 10.1038/s41370-020-0253-z. doi: 10.1038/s41370-020-0253-z URL
[34]	Wallace DR. Nanotoxicology and Metalloestrogens: Possible Involvement in Breast Cancer[J]. Toxics, 2015, 3(4):390-413. doi: 10.3390/toxics3040390. doi: 10.3390/toxics3040390 pmid: 29051471
[35]	曹现岭, 孙振高. 子宫内膜异位症的遗传学发病机制研究进展[J]. 国际生殖健康/计划生育杂志, 2019, 38(1):67-70,82. doi: 10.3969/j.issn.1674-1889.2019.01.014. doi: 10.3969/j.issn.1674-1889.2019.01.014
[36]	Prajapati A, Chauhan G, Shah H, et al. Oncogenic transformation of human benign prostate hyperplasia with chronic cadmium exposure[J]. J Trace Elem Med Biol, 2020, 62:126633. doi: 10.1016/j.jtemb.2020.126633. doi: S0946-672X(20)30198-X pmid: 32818862
[37]	Choudhury C, Mazumder R, Kumar R, et al. Cadmium induced oxystress alters Nrf2-Keap1 signaling and triggers apoptosis in piscine head kidney macrophages[J]. Aquat Toxicol, 2021, 231:105739. doi: 10.1016/j.aquatox.2020.105739. doi: 10.1016/j.aquatox.2020.105739 URL
[38]	Krugner-Higby L, Rosenstein A, Handschke L, et al. Inguinal hernias, endometriosis, and other adverse outcomes in rhesus monkeys following lead exposure[J]. Neurotoxicol Teratol, 2003, 25(5):561-570. doi: 10.1016/s0892-0362(03)00076-x. doi: 10.1016/s0892-0362(03)00076-x pmid: 12972069
[39]	Lai GL, Yeh CC, Yeh CY, et al. Decreased zinc and increased lead blood levels are associated with endometriosis in Asian Women[J]. Reprod Toxicol, 2017, 74:77-84. doi: 10.1016/j.reprotox.2017.09.001. doi: 10.1016/j.reprotox.2017.09.001 URL
[40]	Delsouc MB, Ghersa F, Ramírez D, et al. Endometriosis progression in tumor necrosis factor receptor p55-deficient mice: Impact on oxidative/nitrosative stress and metallomic profile[J]. J Trace Elem Med Biol, 2019, 52:157-165. doi: 10.1016/j.jtemb.2018.12.013. doi: S0946-672X(18)30664-3 pmid: 30732877
[41]	Pollack AZ, Louis GM, Chen Z, et al. Trace elements and endometriosis: the ENDO study[J]. Reprod Toxicol, 2013, 42:41-48. doi: 10.1016/j.reprotox.2013.05.009. doi: 10.1016/j.reprotox.2013.05.009 pmid: 23892002
[42]	Nasiadek M, Stragierowicz J, Klimczak M, et al. The Role of Zinc in Selected Female Reproductive System Disorders[J]. Nutrients, 2020, 12(8):2464. doi: 10.3390/nu12082464. doi: 10.3390/nu12082464 URL