Epigenetic impact of hypothyroidism on the functional differentiation of the mammary gland in rats

Abstract

Mammary gland (MG) lactogenic differentiation involves epigenetic mechanisms. We have previously shown that hypothyroidism(HypoT) alters the MG transcriptome in lactation. However, the role of thyroid hormones (T3 and T4 a.k.a. THs) in epigeneticdifferentiation of MG is still unknown. We used a model of post-lactating HypoT rats to study in MG: a) Methylation and expression levelof Gata3, Elf5, Stat6, Stat5a, Stat5b; b) Expression of Lalba, IL-4Rα and Ncoa1 mRNA; c) Histone H3 acetylation and d) Estrogen andprogesterone concentration in serum. HypoT increases the estrogen serum level, decreases the progesterone level, promotes methylationof Stat5a, Stat5b and Stat6, decreasing their mRNA level and of its target genes (Lalba and IL-4Rα) and increases the Ncoa1 mRNAexpression and histone H3 acetylation level. Our results proved that HypoT alters the post-lactation MG epigenome and couldcompromise mammary functional differentiation.