Macrophage to Myocyte Mitochondrial Transfer in the Myometrium: A Novel Mechanism for the Initiation of Labor

Authors

Nadeem, L., Sharma, A., Shankar, S., Aguiar-Cabeza, E., Pelletier, L., Juriscova, A., Shynlova, O., Lye, S.

Abstract

Labor initiation involves influx of peripheral monocytes into uterine tissue, where they differentiate into macrophages (Macs) and polarize toward pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes. Crosstalk between uterine myocytes (MYO) and Macs is implicated in myometrial activation, but the underlying mechanisms remain unclear. Using immunofluorescence and live-cell imaging, we show that M1-Macs (but not M2-Macs) form tunneling nanotubes (TNT) with MYOs, enabling direct, unidirectional mitochondrial transfer. TNT-mediated mitochondrial transfer enhances ATP production and 20-HSD expression in MYO. Functionally, M1-Macs induce intracellular and functional progesterone (P4) withdrawal in MYOs via 20-HSD mediated P4 metabolism and increased PR-A phosphorylation. In vivo, transfer of monocytes, carrying dendra-labelled mitochondria in pregnant mice confirm their myometrial recruitment, differentiation, polarization to M1-Macs, and M1-Mac/MYO mitochondrial transfer. Increased M1-Macs and mitochondrial transfer to MYOs are observed before labor onset, implicating M1-Macs/MYO interaction as key regulator of labor initiation and potentially a therapeutic target to prevent preterm birth.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 22 Aug 2026.

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