Mots-C
Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1, Mitochondrial-derived peptide MOTS-c
MOTS‑c protects against placental injury via Nrf2 activation in hypoxia‑induced intrauterine growth restriction mice.
Chen. Dan D; Zhao. Hui-Min HM; Sun. Xiao-Lin XL; Xing. Zhi-Xuan ZX; Li. Sheng-Peng SP; Li. Shuai-Chao SC; Wu. Ya-Xian YX; Pang. Qing-Feng QF; Huang. Jian-Feng JF
Key Findings
- Low placental MOTS‑c levels were linked to smaller fetal weight under hypoxia
- MOTS‑c treatment (5 mg/kg) improved fetal growth, increased placental angiogenesis, and reduced oxidative stress in hypoxic mice
- The protective effects required Nrf2 activation; they disappeared in Nrf2‑knockout mice or when Nrf2 was blocked
Practical Outcomes
- MOTS‑c may act as an Nrf2‑activating antioxidant, which is of interest for longevity and metabolic health, but the evidence is limited to a pregnancy model in mice. No human dosing or safety data are available, so any self‑experimentation would be highly experimental and should proceed with caution.
Summary
In a mouse study, giving the tiny peptide MOTS‑c helped protect the placenta from low‑oxygen damage and let babies grow bigger by boosting blood‑vessel growth and cutting oxidative stress, but only when the Nrf2 antioxidant pathway was working. This suggests MOTS‑c can turn on Nrf2, a key defender against oxidative damage, though the work was done in pregnant mice, not people.
Abstract
Intrauterine growth restriction (IUGR) is a leading cause of perinatal morbidity and mortality. Oxidative stress is a key factor in the pathogenesis of IUGR. The transcription factor nuclear factor erythroid 2‑related factor 2 (Nrf2) is a key regulator of the cellular antioxidant response. MOTS‑c, a 16‑amino acid peptide derived from the mitochondria, regulates oxidative stress related pathways. However, the effects of MOTS‑c on IUGR remain unclear. The present study aimed to investigate the role of MOTS‑c in hypoxia‑induced placental restriction and IUGR and its underlying mechanisms. Wild‑type and Nrf2 knockout (KO) maternal mice were exposed to hypoxia from gestational days 11 to 17.5 to establish the IUGR model. Human umbilical vein endothelial cells (HUVECs) were used for <i>in vitro</i> assays. Maternal serum and placenta MOTS‑c concentration were measured using an enzyme‑linked immunosorbent assay. Hematoxylin and eosin staining, reverse transcription‑quantitative PCR, western blotting, immunohistochemistry and immunofluorescence techniques were employed to evaluate the effects of MOTS‑c treatment on IUGR. It was found that reduced placental content of MOTS‑c was positively correlated with low fetal weight in mice with hypoxia‑induced IUGR. The administration of MOTS‑c (5 mg/kg) significantly attenuated hypoxia‑induced IUGR by promoting placental angiogenesis and inhibiting oxidative stress‑mediated placental dysfunction. Furthermore, these protective effects exerted by MOTS‑c were dependent on Nrf2 activation, as administration of MOTS‑c had no protective role in Nrf2 KO mice or HUVECs pre‑treated with ML385, a Nrf2 inhibitor. Taken together, the present study demonstrated that MOTS‑c mitigated placental injury in hypoxia‑induced IUGR by activation of the Nrf2 signaling pathway, thus potentially identifying a novel therapeutic strategy for hypoxia‑induced IUGR.
Study Information
pubmed
2025
2025-11-21T00:00:00.000Z
10.3892/ijmm.2025.5697
67