Related Experiment Video
Updated: May 31, 2026
Establishment of an Experimental Mouse Model of Endometrioma to Study its Related Infertility
Published on: April 5, 2024
Integrative single-cell analysis reveals Bu-Shen-Huo-Xue Formula rescues iron-overloaded ovarian function via
Zhexin Ni1, Qianqian Zhao2, Yangshuo Li2
1Academy of Military Medical Sciences, Beijing 100850, China.
Background:
Ovarian endometriosis (OE) is a leading cause of female infertility. Our previous work identified iron overload-driven oxidative stress and mitochondrial dysfunction in granulosa cells as key pathogenic features, yet the mechanism of the clinically effective Bu-Shen-Huo-Xue Formula (BHF) remains unclear.
Purpose:
To determine how BHF mitigates OE-associated ovarian injury and infertility, and to identify key bioactive constituents and molecular targets.
Methods:
An OE mouse model was treated with BHF to evaluate pelvic adhesions, lesion volume, fibrotic remodeling, and reproductive outcomes. Integrated single-cell RNA sequencing (scRNA-seq) and Stereo-seq were used to define iron overload-associated ovarian niches. Granulosa cell mitochondrial function, ROS, senescence, and BNIP3-PINK1/Parkin-dependent mitophagy were assessed. Serum pharmacochemistry was performed to identify BHF constituents and validate target engagement.
Results:
BHF reduced pelvic adhesions, lesion volume, and fibrotic remodeling, and improved reproductive outcomes in OE mice. Iron overload established a corpus luteum-proximal immuno-fibrotic niche characterized by interferon programs and JAK-STAT activation; BHF attenuated this niche by suppressing CXCL10-mediated immune recruitment and fibroblast activation. At the follicular level, iron overload induced excessive BNIP3-PINK1/Parkin-dependent mitophagy, resulting in mitochondrial dysfunction, ROS accumulation, senescence, and stress-associated metabolic reprogramming; BHF restored mitochondrial homeostasis and alleviated these alterations. Ononin was identified as a major circulating constituent that directly binds BNIP3 and inhibits iron-induced mitophagy, preserving granulosa-cell function.
Conclusion:
BHF acts as a multi-target intervention that protects against OE-associated ovarian injury by dampening iron overload-linked immuno-fibrotic remodeling and restraining BNIP3-dependent mitophagy; ononin is a BNIP3-targeting bioactive component with therapeutic potential.
