Maternal Exposure to 2,4-Di-tert-butylphenol During Pregnancy in a Mouse Model Leads to Abnormal Development of the...

The occurrence of congenital anomalies of the kidney and urinary tract (CAKUT) is influenced by intrauterine environmental factors, and maternal exposure to endocrine-disrupting chemicals (EDCs) during pregnancy may affect the kidney development of offspring. 2,4-Di-tert-butylphenol (2,4-DTBP) is a high-production volume chemical classified as an EDC, which has been detected in humans and has been found to increase mortality and malformation rates in zebrafish embryos. Its effects on mammalian development are still unknown. In this study, a maternal mouse model exposed to 2,4-DTBP throughout pregnancy was established by gavage. The overall conditions of the maternal mice and their offspring were observed, and the concentrations of 2,4-DTBP in maternal serum and offspring tissues were measured using liquid chromatography-tandem mass spectrometry. Exposure to 2,4-DTBP of 75 µg/g·day during pregnancy markedly reduced the early pregnancy rate in mice to 41.75% (95% CI: 33.53-49.97%; n = 139), compared to 82.29% (95% CI: 74.18-90.39%; n = 85) in the controls (p < 0.0001), with a relative risk (RR) of 0.51 (95% CI: 0.41-0.63). 2,4-DTBP could accumulate in maternal mice and be transferred to embryos and internal organs of the offspring, and is associated with the elevated risk of CAKUT in the offspring, primarily manifesting as hydronephrosis/ureteral dilation. The CAKUT rate of DTBP-75 group is 33.59% (95% CI: 17.62-49.56%; N = 9, n = 56), compared to 11.85% (95% CI: 2.43-21.28%; N = 9, n = 67) in the controls (p = 0.02), RR = 2.53 (95% CI: 1.18-5.42). These findings enhance the understanding of the health risks posed by 2,4-DTBP and provide a theoretical basis for environmental monitoring in public health.