Work

The smooth muscle titin filament system regulates uterus contractility and implantation

Year: 2026

Type: article

Abstract: Coordinated uterine peristalsis positions embryos for implantation, but the mechanotransduction pathways controlling uterine wave coordination are not well defined. We combined smooth-muscle-specific deletion of titin M-band exons 1 and 2 with vertical agarose gel electrophoresis, mass spectrometry, uterine ring myography, imaging, transcriptomics, spatial proteomics, and targeted immunoblotting. We show that the myometrium expresses smooth-muscle titin and low-abundance full-length titin including the M-band kinase region. Conditional M-band deletion increased oxytocin-evoked force and area-under-the-curve while reducing coordinated wall motion, yielding fewer as well as crowded/mislocalized implantation sites and heavier placentas. Proteomics and immunoblotting identified disruption of an NBR1/p62 autophagy hub with downstream remodeling of excitability, metabolism, and wall mechanics. Reduced telokin and MLCK levels are consistent with impaired relaxation and increased Ca 2+ -sensitization. Together, these findings establish the titin M-band as a mechanotransductive signaling hub regulating peri-implantation motility with potential clinical relevance for optimizing implantation after in vitro fertilization and preventing ectopic pregnancy.

Source: iScience

DOI: 10.1016/j.isci.2026.117888