2. Academic Validation
  3. Melatonin Enhances the Myometrial Contraction Through MT2-PKC-NRF2/MAFF Signaling Pathway in Sows

Melatonin Enhances the Myometrial Contraction Through MT2-PKC-NRF2/MAFF Signaling Pathway in Sows

  • J Pineal Res. 2026 Mar;78(2):e70135. doi: 10.1111/jpi.70135.
Tongjuan Niu 1 2 3,  Yewen Zhou 1 2 3,  Guobin Qiu 1 2 3,  Jinglin Zhang 2 4,  Jiangpeng Liao 1 2 3,  Qing Zhang 1 2 3,  Shuai Yu 1 2 3,  Kemian Gou 1 2 3,  Sheng Cui 1 2 3,  Di Zhang 1 2 3
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
  • 2 Institute of Reproduction and Metabolism, Yangzhou University, Yangzhou, Jiangsu, China.
  • 3 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, China.
  • 4 Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, China.
PMID: 41854048 DOI: 10.1111/jpi.70135
Abstract

Spontaneous parturition in both humans and sows occurs predominantly at night. Melatonin is thought to facilitate nocturnal parturition in humans by synergistically enhancing myometrial contractions with oxytocin, but the precise underlying mechanisms remain unclear. In this study, in vivo analyses showed that melatonin levels in both serum and myometrium were significantly increased in laboring sows, accompanied by increased melatonin synthesized in the myometrium. Moreover, exogenous melatonin administration to pregnant sows potentially shifted parturition time. Functional studies demonstrated that melatonin supplementation significantly enhanced spontaneous myometrial contractility and sensitivity to oxytocin. Mechanistic investigations revealed that transcription factors NRF2 and MAFF were involved in the signaling pathway of melatonin, enhancing myometrial contractility. Silencing NRF2 or MAFF in melatonin-treated myometrial cells reduced the expression of contraction-associated proteins (CAPs) and attenuated Collagen gel contraction. Dual-luciferase reporter assays indicated that NRF2 and MAFF directly targeted the promoters of key contraction-associated genes, including PTGS2 and OXTR. Additionally, molecular analysis revealed that melatonin enhanced myometrial contraction by binding to the MT2 receptor. Furthermore, our results showed that PKC participated in melatonin-induced myometrial contraction by regulating NRF2 and MAFF expression. Collectively, our data reveal, for the first time, that the MT2-PKC-NRF2/MAFF axis mediates melatonin-enhanced myometrial contraction in sows. These findings advance our understanding of parturition initiation in mammals and may provide a novel theoretical basis for developing therapeutic strategies for preterm or delayed/prolonged labor.

Keywords

MAFF; NRF2; melatonin; myometrial contraction; parturition; sow.

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