Lipoxin A4 inhibits the development of endometriosis in a mouse model by suppressing local estradiol synthesis

Shenzhi Zhao, Zhao S, Xu Z, Zhangye Xu
Prostaglandins & other lipid mediators · 2020 · vol. 153 , pp. 106521 · doi:10.1016/j.prostaglandins.2020.106521 · PMID:33279654 · W3110337273
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Lipoxin A4 reduced endometriosis progression in mice by inhibiting local estradiol production, thereby downregulating disease development.

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Abstract

We investigated whether lipoxin A4 (LXA4) inhibits the development of endometriosis by suppressing local estradiol synthesis. An endometriosis mouse model was constructed by surgical transplantation to subcutanous tissue sites. The treatment group received daily injections of LXA4 (10 μg/Kg) for 21days after which lesions were recovered. We measured 17β-HSD1, 17β-HSD2, CYP11A1, CYP19A1, CYP17A1, and estrogen receptor mRNA expression levels using real-time RT-PCR. In addition, immunohistochemistry was performed to determine protein expression and localization. After LXA4 administration, the volume of endometrial lesions was significantly reduced. Administration of LXA4 resulted in a more rudimentary architecture with a reduced number of developed glands surrounded by a small amount of stroma. LXA4 downregulated the mRNA and protein expression levels of 17β-HSD1, CYP11A1, CYP19A1, CYP17A1, ERα, and ERβ. Furthermore, LXA4 downregulated the expression of ERβ, aromatase expression, and 17β-HSD1 enzyme activity, which affected local estradiol production, resulting in reduced endometriosis. Results from our endometriosis mouse model showed that treatment with LXA4 reduced expression of enzymes and receptors associated or implicated with estrogen-dependent regulation of extra-uterine tissue. We believe that LXA4 has a potential therapeutic value for the treatment of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Disease Models, Animal Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Estradiol Estradiol Lipoxins Lipoxins Animals Aromatase Aromatase Aromatase Female Mice Receptors, Estrogen Receptors, Estrogen Receptors, Estrogen

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