Prenatal Phthalate Exposure, Leptin in Early Childhood, and Mediating Role of DNA Methylation

Currently, research on the association of prenatal phthalate
exposure
with leptin, as well as the mediating role of DNA methylation, is
insufficient. A birth cohort in China was conducted, followed by pregnancy
to early childhood. During the follow-up period, measurements were
conducted for 160 mother-child pairs, including maternal urinary phthalate
concentrations in three trimesters, DNA methylation in cord blood,
and leptin levels in children’s plasma. The present study found
that maternal urinary levels of specific phthalate metabolites, particularly
MiBP (adjusted percent change [95% CI]; −6.62 [−11.73
to −1.22] in the third trimester], MnBP (adjusted percent change
[95% CI]; −7.81 [−14.26 to −0.87] in the second
trimester), ΣDBP (adjusted percent change [95% CI], −9.62
[−16.77 to −1.84] in the second trimester), and ΣLMWP
(adjusted percent change [95% CI], −11.58 [−21.06 to
−0.96] in the second trimester), were negatively associated
with leptin levels in early childhood. Similarly, the phthalate mixture
also showed a more prominent negative association with leptin levels
in the second and third trimesters. Mediation analysis identified
two CpGs that significantly mediated the association between phthalate
exposure and leptin levels, annotated to genes including RORA-AS1, PLCD3, etc. Molecular docking further revealed
that MiBP has a strong binding affinity and good spatial complementarity
with DNA methyltransferases, providing a molecular basis for the association
between MiBP and DNA methylation. In conclusion, prenatal exposure
to MiBP, MnBP, ΣDBP, ΣLMWP, and mixed phthalates was associated
with lower leptin levels in early childhood, possibly due to DNA methylation
changes at multiple sites.