Endometriosis disrupts oocyte metabolism and cortical granule function, impairing fertilization.

Abstract

Background: Endometriosis is a chronic inflammatory disease strongly associated with reduced oocyte quality and subfertility, yet the underlying cytoplasmic defects remain poorly understood.

Methods: Using a surgically induced autologous mouse model, we examined whether endometriosis alters oocyte metabolism, cortical granule (CG) biology, actin architecture, SNARE-regulated exocytosis, fertilization, and early embryonic activation.

Results: Endometriosis markedly increased intracellular reactive oxygen species and altered quinacrine-positive acidic vesicular compartments in ovulated oocytes. Although CG localization was preserved, endometriotic oocytes failed to undergo strontium chloride-induced CG exocytosis. These defects correlated with a significantly thickened cortical F-actin cytoskeleton and a substantial reduction in α-SNAP and NSF levels-two essential regulators of SNARE complex disassembly and membrane fusion. Functionally, endometriotic oocytes exhibited decreased fertilization rates without evidence of polyspermy, while their ability to undergo TPEN-induced parthenogenetic activation and second polar body extrusion remained unchanged.

Conclusions: These findings demonstrate that endometriosis impairs multiple aspects of cytoplasmic maturation-metabolic homeostasis, actin remodeling, and CG exocytotic machinery-ultimately reducing sperm-oocyte fusion efficiency while preserving early embryonic activation capacity. This mechanistic insight provides a foundation for understanding how endometriosis compromises oocyte competence.