Extracorporeal Shock Wave Therapy Combined with Platelet-Rich Plasma during Preventive and Therapeutic Stages of Intrauterine Adhesion in a Rat Model

Yun-Chiao Chang,Ni-Chin Tsai,Jih-Yang Ko,Pei-Ling Weng,Hong-Yo Kang,Kuo-Chung Lan,Yun-Ju Chen,Jai-Hong Cheng,Yin-Hua Cheng

doi:10.3390/biomedicines10020476

Abstract

Intrauterine adhesion (IUA) is caused by artificial endometrial damage during intrauterine cavity surgery. The typical phenotype involves loss of spontaneous endometrium recovery and angiogenesis. Undesirable symptoms include abnormal menstruation and infertility; therefore, prevention and early treatment of IUA remain crucial issues. Extracorporeal shockwave therapy (ESWT) major proposed therapeutic mechanisms include neovascularization, tissue regeneration, and fibrosis. We examined the effects of ESWT and/or platelet-rich plasma (PRP) during preventive and therapeutic stages of IUA by inducing intrauterine mechanical injury in rats. PRP alone, or combined with ESWT, were detected an increased number of endometrial glands, elevated vascular endothelial growth factor protein expression (hematoxylin-eosin staining and immunohistochemistry), and reduced fibrosis rate (Masson trichrome staining). mRNA expression levels of nuclear factor-kappa B, tumor necrosis factor-α, transforming growth factor-β, interleukin (IL)-6, collagen type I alpha 1, and fibronectin were reduced during two stages. However, PRP alone, or ESWT combined with PRP transplantation, not only increased the mRNA levels of vascular endothelial growth factor (VEGF) and progesterone receptor (PR) during the preventive stage but also increased PR, insulin-like growth factor 1 (IGF-1), and IL-4 during the therapeutic stage. These findings revealed that these two treatments inhibited endometrial fibrosis and inflammatory markers, thereby inhibiting the occurrence and development of intrauterine adhesions.

Highlights

We first determined the potential effects of platelet-rich plasma (PRP) and/or Extracorporeal shockwave therapy (ESWT) treatment on body weight in Intrauterine adhesion (IUA)-damaged mouse models
Consistent with the present findings, the mRNA expression levels of nuclear factor-kappa B (NF-κB), IL-6, and tumor necrosis factor (TNF)-α were significantly inhibited following ESWT treatment, E2 transplantation, PRP transplantation, and PRP transplantation combined with ESWT in the two stages (Figure 4B). These findings suggested that ESWT treatment, PRP, and ESWT combined with PRP transplantation regulate fibrosis and inflammation in endometrial stromal cells, during the preventive stage
Our results showed that PRP alone, as well as ESWT combined with PRP in vivo, did not affect body weight but ameliorated endometrial thickness during the preventive stage, but this phenomenon was not observed in the therapeutic stage

Summary

Introduction

Intrauterine adhesion (IUA), known as Asherman syndrome, is a major cause of female secondary infertility [1] and is typically caused by artificial injury to the endometrial. Biomedicines 2022, 10, 476 basal layer of the uterine cavity during curettage, cesarean section, and hysteromyomectomy [2]. IUA commonly occurs due to trauma and infection, leading to the loss of spontaneous endometrium recovery and angiogenesis, initiating the replacement of the normal endometrium by fibrous connective tissue and the formation of adhesions between uterine walls [3]. The incidence of IUA in females who have undergone hysteroscopic surgery and abortion ranges between approximately 4–46% [5]. Clinical data indicate that the prognosis of IUA could be related to failed endometrial regeneration, with a recurrence rate of up to 62.5% [8]. The prevention and early treatment of IUA have become important in recent years

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