Cell type-specific placental signatures in polyendocrine metabolic ovary syndrome and metformin

Abstract

Polyendocrine metabolic ovarian syndrome (PMOS) is associated with adverse pregnancy outcomes and increased cardiometabolic risk in offspring, yet the underlying placental mechanisms remain poorly understood. Metformin is widely prescribed in these pregnancies despite limited mechanistic justification. Here we apply multimodal molecular analyses of placentas from healthy women and from women with PMOS randomized to placebo or metformin, all with uncomplicated pregnancies. PMOS placentas showed transcriptional downregulation across multiple cell types and shifts in cell type proportions. Specifically, syncytiotrophoblasts exhibited reduced expression activity of growth hormone receptor signaling and glycosaminoglycan biosynthesis. Endothelial cells displayed diminished receptor tyrosine kinase pathway activity, including VEGFC, despite increased cell proportion and hypervascularity. Intercellular communication networks were globally suppressed, including reductions in PDGF signaling from Hofbauer cells to fibroblasts. Metformin induced limited molecular changes in PMOS placentas, with associated transcriptional shifts linked to lower birth weight and higher childhood BMI. Our findings revealed cell type-specific alterations in the PMOS placentas that showed limited responsiveness to metformin. This supports further exploration of mechanism-based therapeutic alternatives for future pregnancy management.

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BibTeX RIS

BibTeX

@misc{jiang2026cell,
  title = {{Cell type-specific placental signatures in polyendocrine metabolic ovary syndrome and metformin}},
  author = {H. Jiang and X. Wang and E. Vanky and D. Parreira and E. Derisoud and P. R. Jannig and E. Nordenhok and A. Zhao and C. Li and S. Stridsklev and M. Holzmann and X. Li and C. M. Luthander and E. Stener-Victorin and Q. Deng},
  howpublished = {medRxiv},
  year = {2026},
  month = may,
  doi = {10.64898/2026.05.21.26353338},
  url = {https://www.medrxiv.org/content/10.64898/2026.05.21.26353338v3},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Cell type-specific placental signatures in polyendocrine metabolic ovary syndrome and metformin
AU  - H. Jiang
AU  - X. Wang
AU  - E. Vanky
AU  - D. Parreira
AU  - E. Derisoud
AU  - P. R. Jannig
AU  - E. Nordenhok
AU  - A. Zhao
AU  - C. Li
AU  - S. Stridsklev
AU  - M. Holzmann
AU  - X. Li
AU  - C. M. Luthander
AU  - E. Stener-Victorin
AU  - Q. Deng
PY  - 2026
DA  - 2026/05/21
PB  - medRxiv
DO  - 10.64898/2026.05.21.26353338
UR  - https://www.medrxiv.org/content/10.64898/2026.05.21.26353338v3
AB  - Polyendocrine metabolic ovarian syndrome (PMOS) is associated with adverse pregnancy outcomes and increased cardiometabolic risk in offspring, yet the underlying placental mechanisms remain poorly understood. Metformin is widely prescribed in these pregnancies despite limited mechanistic justification. Here we apply multimodal molecular analyses of placentas from healthy women and from women with PMOS randomized to placebo or metformin, all with uncomplicated pregnancies. PMOS placentas showed transcriptional downregulation across multiple cell types and shifts in cell type proportions. Specifically, syncytiotrophoblasts exhibited reduced expression activity of growth hormone receptor signaling and glycosaminoglycan biosynthesis. Endothelial cells displayed diminished receptor tyrosine kinase pathway activity, including VEGFC, despite increased cell proportion and hypervascularity. Intercellular communication networks were globally suppressed, including reductions in PDGF signaling from Hofbauer cells to fibroblasts. Metformin induced limited molecular changes in PMOS placentas, with associated transcriptional shifts linked to lower birth weight and higher childhood BMI. Our findings revealed cell type-specific alterations in the PMOS placentas that showed limited responsiveness to metformin. This supports further exploration of mechanism-based therapeutic alternatives for future pregnancy management.
ER  -

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