Flow-driven lumen remodeling and valve opening in the vas deferens

• 成果类型: Article
• 署名作者: Ying, Nicole Ng Shu; Lim, Qin Ying; Yamada, Gen; Hirashima, Tsuyoshi
• 署名单位: National University of Singapore; National University of Singapore; Kyoto University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2538135123
• 发表日期: 2026-09-15
• 页码: e2538135123
• 关键词: intravital imaging; male reproduction; mechano-signaling coupling; sperm transport; vas deferens; FLUID TRANSPORT; RHO-KINASE; contractility; noradrenaline; responses; subtypes; mice; EPIDIDYMIDIS; nerve

摘要

Biological ducts must transport fluids while preserving structural integrity, yet how mechano-signaling coordinates wall deformation with luminal flow in vivo remains unclear. Here, we combine intravital two-photon excitation microscopy, light-sheet imaging, and F & ouml;rster resonance energy transfer-based kinase biosensors to resolve ejaculation-like events in the mouse vas deferens. Acute phenylephrine stimulation elicits a sequence of luminal dynamics: an initial retrograde pressure-redistribution wave followed by a ballistic antegrade flow that propels dense sperm suspensions from the proximal to the distal duct. This contraction-driven flow opens a normally collapsed, wrinkled distal segment, driving progressive lumen expansion and unfolding of epithelial wrinkles. We show that the vas deferens actively modulates luminal geometry in response to these flow dynamics: ROCK activity in smooth muscle is required for global contraction and cAMP-associated signaling modulates this contractile response. By contrast, extracellular signal-regulated kinase activity in circumferential smooth muscle is dispensable for the ductal contraction but essential for active, flow-dependent remodeling of the distal lumen, forming the core of the mechano-signaling module that couples sperm flow to valve opening. These findings establish the vas deferens as an experimentally tractable model of ductal tissue hydraulics and reveal a mechano-signaling framework by which a tubular organ converts transient muscular input into robust, directional luminal transport.