Elevated contractility drives implantation failure in mouse embryos from aged females

Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung

Beitragende

  • Kate E. Cavanaugh - , University of California at San Francisco (Autor:in)
  • M. J. Franco-Oñate - , Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD) (Autor:in)
  • Nicole Horsley - , Stanford University (Autor:in)
  • Dilan Gokyer - , Northwestern University (Autor:in)
  • Tomiris Atazhanova - , Northwestern University (Autor:in)
  • Diana J. Laird - , University of California at San Francisco (Autor:in)
  • Patrick W. Oakes - , Loyola University Chicago (Autor:in)
  • Joan K. Riley - , Northwestern University (Autor:in)
  • Francesca E. Duncan - , Northwestern University (Autor:in)
  • Mary Ellen Pavone - , Northwestern University (Autor:in)
  • Matteo Molé - , Stanford University (Autor:in)
  • Ricard Alert - , Max-Planck-Institut für Physik komplexer Systeme, Zentrum für Systembiologie Dresden (CSBD), Technische Universität Dresden, Universitat de Barcelona, ICREA - Institució Catalana de Recerca i Estudis Avançats (Autor:in)
  • Orion D. Weiner - , University of California at San Francisco (Autor:in)

Abstract

Women in their mid-30s experience a marked decline in fertility. The origin of these fertility defects resides in the implantation capacity of the embryo itself, but the mechanistic basis of this impairment is not well understood. Here we identify a core mechanical defect in embryos from aged females that impairs their implantation competence. Using mouse models, we find that reproductive ageing drives excessive contractility in the trophectoderm, the outer epithelial lineage that enables implantation. This hypercontractility increases blastocyst tissue surface tension and viscosity, which hinders spreading during implantation. Elevated contractility is both necessary and sufficient for age-associated implantation failure. We identify non-invasive imaging signatures that infer embryo mechanics and predict implantation success for embryos of both young and aged females. Analyses of human embryos and in vitro fertilization clinical datasets reveal conserved age-associated mechanical alterations that correlate with implantation potential. Our work implicates embryo mechanics as a key regulator of reproductive longevity.

Details

OriginalspracheEnglisch
Seiten (von - bis)1799-1813
Seitenumfang15
FachzeitschriftNature cell biology
Jahrgang28
Ausgabenummer9
Frühes Online-Datum25 Aug. 2026
PublikationsstatusVeröffentlicht - Sept. 2026
Peer-Review-StatusJa

Externe IDs

PubMed 42642655

Schlagworte

ASJC Scopus Sachgebiete