Metabolomics Analysis Discovers Estrogen Altering Cell Proliferation via the Pentose Phosphate Pathway in Infertility Patient Endometria.

Yingxin Zheng,Ting Zhuge,Bin Li,Yuemeng Zhu,Chao Gu

doi:10.3389/fendo.2021.791174

Yingxin Zheng, Ting Zhuge + Show 3 more

Open Access

https://doi.org/10.3389/fendo.2021.791174

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Abstract

Estrogen therapy is widely used as a supplementary treatment after hysteroscopy for female infertility patients owing to its protective function that improves endometrial regeneration and menstruation, inhibits recurrent adhesions, and improves subsequent conception rate. The endometrial protective function of such estrogen administration pre-surgery is still controversial. In the current study, 12 infertility patients were enrolled, who were treated with estrogen before hysteroscopy surgery. Using cutting-edge metabolomic analysis, we observed alterations in the pentose phosphate pathway (PPP) intermediates of the patient’s endometrial tissues. Furthermore, using Ishikawa endometrial cells, we validated our clinical discovery and identified estrogen–ESR–G6PD–PPP axial function, which promotes estrogen-induced cell proliferation.

Highlights

Infertility is defined as a failure to fall pregnant despite a couple having regular unprotected sexual intercourse for over 1 year [1]
There is a risk that estrogen treatment during the endometrial proliferative phase may induce side effects, including endometrial hyperplasia and endometrial cancer; it is necessary to investigate biological signaling, especially metabolomic alteration after estrogen treatment in infertility patients
The metabolomic results indicated that estrogen can affect metabolic changes in patient’s endometrial tissues (Figure 1B), and most of them are associated with phosphate pathway (PPP) metabolism

Summary

Introduction

Infertility is defined as a failure to fall pregnant despite a couple having regular unprotected sexual intercourse for over 1 year [1]. Infertility has multiple causes, regular screening, including semen analysis (morphology and motility, etc.), assessment of tubal patency, and detection of ovulation over a period of 1 year of regular unprotected sexual intercourse is normally sufficient to identify the problem. There are five factors that are commonly identified in the female reproductive system that could cause clinical infertility; [1] diminished ovarian reserve or ovulatory dysfunction (25%–30%); [2] tubal disease or blockage (20%–25%); [3] endometriosis (10%–20%); [4] uterine abnormalities such as cervical polyps, submucous uterine myoma, intrauterine adhesion, endometrial hyperplasia, and uterine malformation (0%–5%); and [5] unexplained infertility (25%– 30%) [3,4,5,6,7,8]. Fallopian tubes and uterine abnormalities are the main causes of female infertility, and hysteroscopy is able to diagnose the pathological factors and treat such disorders effectively [9]. The beneficial therapeutic effects of hysteroscopic surgery have been demonstrated by Longfa et al, some complications such as the formation of intrauterine adhesions post-operatively cannot be ignored [12]

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