Developmental manganese exposure, but not concurrent lead, alters social processing selectively in male mice

Exposure to multiple environmental pollutants, including heavy metals, during fetal life and early childhood, represents a major public health concern. Although the effects of exposure to a single metal are well documented, the impact of combined exposure to two or more metals remains underexplored. We investigated the neurobehavioral effects and hippocampal transcriptome changes in mouse offspring whose mothers were exposed to lead (Pb) and manganese (Mn), individually and in combination, via drinking water from two weeks prior to conception until the end of lactation. Developmental Mn exposure selectively impaired social recognition in adult males, an effect that disappeared when exposure occurred in combination with Pb exposure. Interestingly, the antagonistic interaction between Pb and Mn was further supported by biomonitoring and transcriptomic data. The latter also revealed sex-dependent vulnerability, especially to Pb, with males exhibiting a greater number of deregulated genes than females.