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Updated: Jul 19, 2025
Isolation of Human Endometrial Stromal Cells for In Vitro Decidualization
Published on: September 1, 2018
Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target
Hanxi Zheng1,2, Xishi Liu1,3, Sun-Wei Guo3,4
1Department of Gynecology, Shanghai Obstetrics and Gynecology Hospital Fudan University Shanghai China.
Purpose:
To screen Zn2+-dependent histone deacetylase (HDAC) 1-11 in endometriotic cells and then evaluated the HDACs identified from the screening in ovarian endometrioma (OE) and deep endometriotic (DE) lesions, and to evaluate the therapeutic potential of HDAC8 inhibition in mice.
Methods:
Quantification of gene and protein expression levels of HDAC1-11 in endometriotic cells stimulated by TGF-β1, and immunohistochemistry analysis of Class I HDACs and HDAC6 in OE/DE lesion samples. The therapeutic potential of HDAC8 inhibition was evaluated by a mouse model of deep endometriosis.
Results:
The screening identified Class I HDACs and HDAC6 as targets of interest. Immunohistochemistry analysis found a significant elevation in HDAC8 immunostaining in both OE and DE lesions, which was corroborated by gene and protein expression quantification. For other Class I HDACs and HDAC6, their lesional expression was more subtle and nuanced. HDAC1 and HDAC6 staining was significantly elevated in DE lesions while HDAC2 and HDAC3 staining was reduced in DE lesions. Treatment of mice with induced deep endometriosis with an HDAC8 inhibitor resulted in significantly longer hotplate latency, a reduction of lesion weight by nearly two-thirds, and significantly reduced lesional fibrosis.
Conclusions:
These findings highlight the progression-dependent nature of specific HDAC aberrations in endometriosis, and demonstrate, for the first titme, the therapeutic potential of suppressing HDAC8.
Insights
Histone deacetylase (HDAC) 8 is elevated in endometriosis lesions. Inhibiting HDAC8 reduced lesion size and fibrosis in mice, showing therapeutic potential for endometriosis treatment.
Area of Science:
- Reproductive biology
- Molecular oncology
- Epigenetics
Background:
- Endometriosis is a complex gynecological disorder.
- Histone deacetylases (HDACs) play a role in gene regulation and cellular processes.
- Aberrant HDAC expression is implicated in various diseases, including cancer and endometriosis.
Purpose of the Study:
- To screen Zn2+-dependent HDACs (1-11) in endometriotic cells.
- To evaluate identified HDACs in ovarian endometrioma (OE) and deep endometriotic (DE) lesions.
- To assess the therapeutic potential of HDAC8 inhibition in a mouse model of endometriosis.
Main Methods:
- HDAC1-11 gene and protein expression quantified in endometriotic cells stimulated by TGF-β1.
- Immunohistochemistry performed on OE/DE lesion samples for Class I HDACs and HDAC6.
- HDAC8 inhibition efficacy evaluated in a mouse model of deep endometriosis.
Main Results:
- Class I HDACs and HDAC6 identified as targets of interest.
- HDAC8 immunostaining significantly elevated in both OE and DE lesions.
- HDAC8 inhibition in mice reduced lesion weight by nearly two-thirds and decreased fibrosis.
Conclusions:
- HDAC aberrations in endometriosis are progression-dependent.
- HDAC8 inhibition demonstrates significant therapeutic potential for endometriosis.
- Targeting HDAC8 offers a promising avenue for endometriosis treatment.
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