Maternal Melatonin Contributes to Offspring Hair Follicle Development Through Transcriptional Regulation of the AP-1 Complex and MAPK Pathway

Maternal melatonin (MT) readily crosses the placental barrier to enter the fetal circulation, and it holds the potential to enhance hair follicle (HF) development, possibly augmented through nutritional interventions during pregnancy. However, the specific impact of maternal MT treatment on fetal HF development remains largely unexplored. In this study, we implanted pregnant rabbits with 10 mg of MT-containing and non-MT-containing silica gel microcapsules. We then assessed HF density and the extent of HF cell apoptosis in the neonatal rabbits. Our findings revealed that maternal MT implantation significantly reduced HF cell apoptosis and promoted an increased HF density in the neonates. Mechanistically, this process involved MT downregulating the expression of JUN/FOS and AP-1, while concurrently upregulating equol expression and reducing norepinephrine levels. Analysis of key protein expression within the MAPK pathway indicated that maternal MT activated this pathway. These results suggest that maternal MT treatment promotes beneficial HF development in offspring. Notably, the transcriptional regulation of JUN/FOS members of the AP-1 complex emerges as a pivotal factor mediating the beneficial effects of MT on neonatal hair follicle development.