Chromium levels in placental tissue and neural tube defects: Association and mechanistic study

Yongyan Chen; Yingnan Guo; Chengrong Wang; Jufen Liu; Lei Jin; Zhiwen Li; Aiguo Ren; Linlin Wang

doi:10.1016/j.envpol.2024.124126

Chromium levels in placental tissue and neural tube defects: Association and mechanistic study

Environ Pollut. 2024 May 10:352:124126. doi: 10.1016/j.envpol.2024.124126. Online ahead of print.

Authors

Yongyan Chen¹, Yingnan Guo¹, Chengrong Wang¹, Jufen Liu¹, Lei Jin¹, Zhiwen Li¹, Aiguo Ren¹, Linlin Wang²

Affiliations

¹ Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
² Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China. Electronic address: linlinwang@bjmu.edu.cn.

PMID: 38735460
DOI: 10.1016/j.envpol.2024.124126

Abstract

Human exposure to chromium (Cr) is common but little is known about its adverse effects on pregnancy outcomes. This study aimed to explore the association between Cr exposure and the risk of neural tube defects (NTDs) and the underlying mechanisms of Cr-induced NTDs. 593 controls and 408 NTD cases with placentas were included in this study. Chromium trichloride (Cr(III)) and potassium dichromate (Cr(VI)) were intragastrically administered to pregnant mice and the number of NTDs was recorded. The odds ratio for total NTDs in the highest exposure group in placenta was 4.18 (95% confidence interval (CI), 1.97-8.84). The incidence of fetal NTDs in mice administered with Cr(III) showed a dose-response relationship. Cr(VI) didn't show teratogenicity of NTDs whereas increased the stillbirth rate. Prenatal exposure to Cr(III) increased levels of oxidative stress and apoptosis in fetal mice. RNA-sequencing results indicated significant enrichment of the MAPK pathway. RT-qPCR and Western blot analysis revealed that Cr(III) induced increased expression of p-JNK, p-P38, and Casp3. Toxicological effects can be partly antagonized by antioxidant supplementation. High chromium exposure was associated with increased human NTD risks. Excessive Cr(III) exposure can induce NTDs in fetal mice by increasing apoptosis through upgrading oxidative stress and then activating JNK/P38 MAPK signaling pathway.

Keywords: Birth defects; Chromium; JNK/ P38 MAPK signaling pathways; Neural tube defects.