Juppi, H.-K.; Korhonen, T.-M.; Sievanen, T.; Kovanen, V.; Kujala, U. M.; Aukee, P.; Cronin, N.; Sipila, S.; Karvinen, S.; Laakkonen, E. K.

Menopause is associated with unfavorable changes in body composition. Skeletal muscle cells are targets of hormonal regulation and are affected by the interplay between coding and non-coding RNAs. Muscle transcriptome, including messenger-RNA (mRNA), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) has not previously been studied in women during the menopausal transition. Thus, we took a multi-RNA omics approach to get insight into transcriptome-wide events of menopause. Our study included baseline and follow-up muscle samples from seven early (EarlyMT) and 17 late perimenopausal (LateMT) women transitioning to early postmenopause during the study. Total RNA was sequenced and differential expression (DE) of the transcriptome was investigated. The potential gene functions were investigated with pathway analyses and protein level expression with Western Blot. We found 30 DE mRNA genes in EarlyMT and 19 in LateMT participating in pathways controlling cell death, growth, and interactions with external environment. Lack of protein level changes may indicate a specific role of the regulatory RNAs during menopause. Ten DE lncRNA transcripts were identified but did not result in DE lncRNAs genes. No DE miRNAs were found. Despite the lack of DE findings in regulatory RNAs, we identified putative regulatory networks, likely to be affected by estradiol availability. The changes in gene expression were correlated with observed changes in body composition variables, indicating muscularity and adiposity regulators to be affected by menopausal transition. In essence, the observed DE genes and their regulatory networks may offer novel mechanistic insights on factors affecting body composition during and after menopause.