Picture the liver as an orchestra with two different scores: one for boys, one for girls. Sex hormones and growth hormone conduct these scores. If fake conductors, harmful substances from the environment, step into the orchestra pit early in life, they start rewriting the notes.
Scientists gave mice seven different toxicants (arsenic, lead, bisphenol A and others) from two weeks before the parents mated until three weeks after birth. The animals were then raised free of exposures, and their livers were checked at three weeks, five months and ten months. Each toxicant made its own edits, and the edits in males and females hardly overlapped. In males, gene activity changed more often; in females, chemical marks on DNA did. Most importantly, the toxicants scrambled the natural sex differences. In males, many male genes fell silent while female genes woke up instead. For example, exposure to tributyltin lowered the activity of 38 male genes and raised the activity of 10 female genes in males.
This means early exposures do not just cause temporary glitches; they reprogram the liver's sex program, and males are more prone to this feminization. Toxicants were already known to harm the liver, but it was unclear how they act at the molecular level in each sex. Now we know that every toxicant leaves a unique signature, and these signatures barely overlap between males and females. This helps explain why men and women have different susceptibilities to liver disease, and it could lead to biomarkers of early exposure.
Only two genes kept altered expression across all three life stages: Tmem200b in females exposed to PM2.5-CHI and Ces1d in males exposed to lead. The other thousands of changes came and went with age.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.