2. Academic Validation
  3. MCT1 supports syncytiotrophoblast function and placental development in early pregnancy

MCT1 supports syncytiotrophoblast function and placental development in early pregnancy

  • J Reprod Immunol. 2025 Dec 29:173:104829. doi: 10.1016/j.jri.2025.104829.
Ruizhi Chen 1,  Jiahui Xiao 2,  Guanying You 2,  Linlin Wang 2,  Gang Feng 2,  Lianghui Diao 3,  Yuye Li 4
Affiliations

Affiliations

  • 1 Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Guangdong Engineering Technology Research Center of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics, Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), Shenzhen, China; Laboratory for Experimental Feto-Maternal Medicine, Department of Gynecology and Obstetrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg Center for Translational Immunology, University Medical Center Hamburg, Eppendorf, Hamburg, Germany.
  • 2 Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Guangdong Engineering Technology Research Center of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics, Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), Shenzhen, China.
  • 3 Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Guangdong Engineering Technology Research Center of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics, Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), Shenzhen, China. Electronic address: [email protected].
  • 4 Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Guangdong Engineering Technology Research Center of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics, Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), Shenzhen, China. Electronic address: [email protected].
PMID: 41478132 DOI: 10.1016/j.jri.2025.104829
Abstract

Spontaneous miscarriage affects approximately 15 % of clinically recognized pregnancies, often due to impaired placental development. While syncytiotrophoblast (STB) is essential for nutrient exchange and hormonal support, the molecular pathways that maintains function remain incompletely defined. Here, we identify Monocarboxylate Transporter 1 (MCT1) as a novel metabolic regulator of placental development. We show that MCT1 expression is markedly reduced in the villi of patients with spontaneous miscarriage, correlating with abnormal lactate accumulation. Using a mouse model, we demonstrate that MCT1 inhibition leads to pregnancy failure and impaired formation of the placental labyrinth, the key site for maternal-fetal exchange. Functional and transcriptomic analyses reveal that MCT1 deficiency disrupts syncytiotrophoblast organization and downregulates transcriptional regulators critical for trophoblast function. These findings suggest that MCT1 supports early pregnancy through the trophoblast gene regulatory networks and identify it as a potential target in reproductive failure.

Keywords

Labyrinth; Lactic acid; MCT1; Syncytiotrophoblast; Transcriptional regulation.

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