Related Experiment Video
Updated: Nov 13, 2025
Establishment of an Experimental Mouse Model of Endometrioma to Study its Related Infertility
Published on: April 5, 2024
Target identification and drug discovery by data-driven hypothesis and experimental validation in ovarian
Minuo Yin1, Jiaming Zhang2, Xinliu Zeng1
1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Objective:
To identify targets and discover drugs for ovarian endometriosis (OE) DESIGN: A basic study based on a data-driven hypothesis and experimental validation SETTING: Center for Reproductive Medicine PATIENT(S)/ANIMAL(S): Fourteen patients with OE and 7 healthy donors were recruited, and 15 female C57/BL6 mice were involved.
Intervention(S):
Samples of OE lesions and normal endometrium were obtained. The ITPR1-knockdowned ectopic human endometrial stromal cells (HESCs) were subjected to ribonucleic acid (RNA) sequencing, cell-counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, and flow cytometry. Camptothecin was administered to HESCs and in an OE mouse model.
Main Outcome Measure(S):
ITPR1 expression in OE lesions and normal endometrium, cell proliferation and apoptosis of HESCs with ITPR1 knockdown or camptothecin treatment, and autograft volume in the OE mouse model RESULT(S): Two significant OE-relevant gene modules were identified and involved the PI3K/Akt and aging-relevant pathways. Fifteen hub genes were identified and confirmed, among which the most significant gene, ITPR1, was robustly elevated in OE lesions. RNA sequencing revealed that ITPR1 was highly relevant to cell proliferation and apoptosis, which was further confirmed by CCK-8 assay, EdU staining, and flow cytometry analysis. ITPR1 knockdown inhibited cell proliferation and induced HESC apoptosis. The candidate drugs targeting these modules were screened, among which camptothecin and irinotecan were identified as promising drugs. Both compounds suppressed HESC proliferation and induced apoptosis; ITPR1 expression was suppressed by camptothecin. The therapeutic effect of camptothecin was also validated in the OE mouse model.
Conclusion(S):
This study identified the therapeutic targets and promising drugs for OE and shed light on the use of camptothecin in OE treatment.
Insights
Researchers identified inositol trisphosphate 3-kinase A (ITPR1) as a key target for ovarian endometriosis (OE). Camptothecin effectively reduced OE cell growth and tumor size in a mouse model, showing therapeutic potential.
Area of Science:
- Reproductive biology
- Molecular medicine
- Genetics
Background:
- Ovarian endometriosis (OE) is a debilitating condition requiring novel therapeutic targets.
- Current treatment options for OE have limitations, necessitating the discovery of new drugs.
Purpose of the Study:
- To identify key molecular targets for ovarian endometriosis (OE).
- To discover and validate potential drug candidates for OE treatment.
Main Methods:
- Analysis of gene expression in OE lesions and normal endometrium.
- In vitro studies using human endometrial stromal cells (HESCs) with ITPR1 knockdown.
- In vivo validation using an OE mouse model treated with camptothecin.
Main Results:
- Inositol trisphosphate 3-kinase A (ITPR1) was significantly elevated in OE lesions and linked to cell proliferation.
- ITPR1 knockdown inhibited HESC proliferation and induced apoptosis.
- Camptothecin demonstrated efficacy in suppressing OE cell growth and reducing tumor burden in mice, with ITPR1 downregulation observed.
Conclusions:
- ITPR1 is a promising therapeutic target for ovarian endometriosis.
- Camptothecin shows significant therapeutic potential for OE treatment.
