Establishment of an Artificial Neural Network Model Using Immune-Infiltration Related Factors for Endometrial Receptivity Assessment.

Bohan Li,Hua Duan,Yazhu Li,Sha Wang,Jiajing Wu

doi:10.3390/vaccines10020139

Bohan Li, Hua Duan + Show 3 more

Open Access

https://doi.org/10.3390/vaccines10020139

Copy DOI

Abstract

Background: A comprehensive clinical strategy for infertility involves treatment and, more importantly, post-treatment evaluation. As a component of assessment, endometrial receptivity does not have a validated tool. This study was anchored on immune factors, which are critical factors affecting embryonic implantation. We aimed at establishing novel approaches for assessing endometrial receptivity to guide clinical practice. Methods: Immune-infiltration levels in the GSE58144 dataset (n = 115) from GEO were analysed by digital deconvolution and validated by immunofluorescence (n = 23). Then, modules that were most associated with M1/M2 macrophages and their hub genes were selected by weighted gene co-expression network as well as univariate analyses and validated using the GSE5099 macrophage dataset and qPCR analysis (n = 19). Finally, the artificial neural network model was established from hub genes and its predictive efficacy validated using the GSE165004 dataset (n = 72). Results: Dysregulation of M1 to M2 macrophage ratio is an important factor contributing to defective endometrial receptivity. M1/M2 related gene modules were enriched in three biological processes in macrophages: antigen presentation, interleukin-1-mediated signalling pathway, and phagosome acidification. Their hub genes were significantly altered in patients and associated with ribosomal, lysosomal, and proteasomal pathways. The established model exhibited an excellent predictive value in both datasets, with an accuracy of 98.3% and an AUC of 0.975 (95% CI 0.945–1). Conclusions: M1/M2 polarization influences endometrial receptivity by regulating three gene modules, while the established ANN model can be used to effectively assess endometrial receptivity to inform pregnancy and individualized clinical management strategies.

Highlights

Endometrial receptivity is a complex process that enables embryonic attachment, invasion, and development
We found that a moderate increase in M1/M2 in window of implantation (WOI) is beneficial for embryonic implantation
We found an imbalance between M1 and M2 macrophages, we performed the diagnosis by expression of factors in different gene modules instead of direct microscopic counts to improve reproducibility of the results and reduce measurement errors associated with subjectivity

Summary

Introduction

Endometrial receptivity is a complex process that enables embryonic attachment, invasion, and development. Defective endometrial receptivity is often associated with repeated implantation failure (RIF), embryonic loss and unexplained infertility. The current diagnostic tests for endometrial receptivity disorders include sonography, histopathology, and electron microscopy of endometrial cell morphologies These methods have a limited clinical guidance [2]. M1/M2 related gene modules were enriched in three biological processes in macrophages: antigen presentation, interleukin-1-mediated signalling pathway, and phagosome acidification. Their hub genes were significantly altered in patients and associated with ribosomal, lysosomal, and proteasomal pathways. Conclusions: M1/M2 polarization influences endometrial receptivity by regulating three gene modules, while the established ANN model can be used to effectively assess endometrial receptivity to inform pregnancy and individualized clinical management strategies

Methods

Findings

Discussion

Conclusion