Altered placental expression of small humanin-like peptides in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is characterized by maternal insulin resistance and hyperglycemia and has been associated with placental mitochondrial alterations. Small humanin-like peptides (SHLP1-6), encoded within the mitochondrial 16S rRNA region, have been described as mitochondria-derived peptides (MDPs) with reported cytoprotective and metabolic effects in experimental settings. However, their expression in placental tissues from GDM pregnancies has not been previously investigated.

Placental tissues were obtained from women with GDM and normoglycemic controls following cesarean delivery. Maternal fasting glucose, fasting insulin, glycated hemoglobin A1c (HbA1c), and the homeostatic model assessment for insulin resistance (HOMA-IR) were recorded. Total RNA was isolated from placental samples, and the mRNA expression levels of SHLP1-6 were quantified using quantitative real-time polymerase chain reaction (PCR). In addition, Humanin and SHLP2 peptide levels were assessed at the protein level. Group comparisons and correlation analyses were performed to evaluate associations between placental SHLP expression and maternal metabolic parameters within each group.

Placental expression levels of all six SHLP transcripts were significantly reduced in the GDM group compared with controls. Lower placental SHLP expression was significantly associated with higher HOMA-IR and HbA1c values. In addition, reduced SHLP transcript levels were associated with increased neonatal birth weight. Consistently, Humanin and SHLP2 levels were significantly reduced in both serum and placental samples in the GDM group.

This study demonstrates that placental mRNA levels of SHLPs are reduced in pregnancies complicated by GDM and are associated with maternal metabolic status. The integration of transcriptional findings with targeted peptide measurements supports the notion that altered placental SHLP expression is linked to metabolic disturbances in GDM and warrants further investigation into the role of MDPs in placental adaptation during diabetic pregnancy.