Transcriptome-Based Analysis Reveals Therapeutic Effects of Resveratrol on Endometriosis in aRat Model

Abstract

Introduction

Endometriosis (EMs) is associated with severe chronic pelvic pain and infertility and the development of improved EMs treatment options is an ongoing focus. In this study, we investigated the effects of resveratrol on EMs and analyzed transcriptional changes in the lesions of model rats before and after resveratrol treatment.

Methods

We established arat model of endometriosis through the trans-implantation of endometrial fragments to the peritoneal wall and then used resveratrol as treatment. We then analyzed the results using RNA sequencing of the lesion tissues of each of the model rats before resveratrol treatment and the reduced lesion tissues after the treatment. Examinations of anatomy, biochemistry, immunohistochemical staining and flow cytometry examinations were also conducted. Other trans-implanted rats were also given sham treatments as sham-treatment control and other untrans-implanted rats served as sham-operation controls.

Results

In addition to the obvious lesions observed in the model rats, there were significant differences in the glucose tolerance, macrophage M1/M2 polarization, and adipocyte sizes between the treated model rats and sham (control) rats. Resveratrol treatment in the model rats showed significant efficacy and positive therapeutic effect. Transcriptional analysis showed that the effects of resveratrol on the endometriosis model rats were manifested by alterations in the PPAR, insulin resistance, MAPK and PI3K/Akt signaling pathways. Correspondingly, changes in PPARγ activation, M1/M2 polarization and lipid metabolism were also detected after resveratrol treatment.

Discussion

Our study revealed that resveratrol treatment displayed efficient therapeutic effects for EMs model rats, probably through its important roles in anti-inflammation, immunoregulation and lipid-related metabolism regulation.

Keywords:

• endometriosis
• resveratrol
• RNA-seq
• glucose tolerance
• PPARγ

Acknowledgments

We are very grateful to Chris Wood from the Life Science College of Zhejiang University for language support. Thanks to Liuping and Feiyu Feng for providing help in the raising experimental animals in the Laboratory Animal Center of Zhejiang University.

Abbreviations

EMs, endometriosis; Padj, adjusted pvalue; FC, fold change; KGEE, Kyoto Encyclopedia of Genes and Genomes; GTT, glucose tolerance test; ITT, insulin tolerance test; MAPK, mitogen-activated protein kinases.1; SEM, standard error of mean; PPARs, peroxisome proliferators-activated receptors; AKT, protein kinase B.

Ethics in Publishing

All animal experiments were approved by the Zhejiang University Experimental Animal Welfare Ethics Review Committee. The treatment and welfare of animals strictly followed the Laboratory Animal-Guideline for Ethical Review of Animal Welfare (GB/T 35892-2018) issued by the Zhejiang University Experimental Animal Welfare Ethics Review Committee.

Author Contributions

All authors made asignificant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors have declared that no conflict of interest exists.

Additional information

Funding

This work was funded by The National Key R&D Program of China (2018YFC1004900, 2018YFC1003201), Natural Science Foundation of China (grant 82071616), Zhejiang National Science Foundation (LGF20H040010, LY17H040004, LY19H040011).