Predicted COVID-19 molecular effects on endometrium reveal key dysregulated genes and functions

Fecha de publicación: 28/10/2022 Fecha Ahead of Print: 01/10/2022

Autores de IIS La Fe

Ismael Henarejos Castillo

Autor
Almudena Devesa Peiró

Autor
Lucia De Miguel Gómez

Autor
Patricia Sebastián León

Autor
Mónica Romeu Villarroya

Autor
Alejandro Alemán Ramos

Autor
Antonio Pellicer Martínez

Autor
Irene Cervelló Alcaraz

Autor
Patricia Díaz Gimeno

Autor

Participantes ajenos a IIS La Fe

Molina-Gil, C.

Grupos

Biología Reproductiva y Bioingeniería en Reproducción Humana

Leader

Nicolás Garrido Puchalt
Biomarcadores, Medicina Genómica, Estadística y Análisis masivo de datos en Reproducción humana asistida

Investigador Principal

Marcos Meseguer Escrivá
Medicina Reproductiva

Investigador Principal

José Morales Roselló

Abstract

COVID-19 exerts systemic effects that can compromise various organs and systems. Although retrospective and in silico studies and prospective preliminary analysis have assessed the possibility of direct infection of the endometrium, there is a lack of in-depth and prospective studies on the impact of systemic disease on key endometrial genes and functions across the menstrual cycle and window of implantation. Gene expression data have been obtained from (i) healthy secretory endometrium collected from 42 women without endometrial pathologies and (ii) nasopharyngeal swabs from 231 women with COVID-19 and 30 negative controls. To predict how COVID-19-related gene expression changes impact key endometrial genes and functions, an in silico model was developed by integrating the endometrial and COVID-19 datasets in an affected mid-secretory endometrium gene co-expression network. An endometrial validation set comprising 16 women (8 confirmed to have COVID-19 and 8 negative test controls) was prospectively collected to validate the expression of key genes. We predicted that five genes important for embryo implantation were affected by COVID-19 (downregulation of COBL, GPX3 and SOCS3, and upregulation of DOCK2 and SLC2A3). We experimentally validated these genes in COVID-19 patients using endometrial biopsies during the secretory phase of the menstrual cycle. The results generally support the in silico model predictions, suggesting that the transcriptomic landscape changes mediated by COVID-19 affect endometrial receptivity genes and key processes necessary for fertility, such as immune system function, protection against oxidative damage and development vital for embryo implantation and early development.

Datos de la publicación

ISSN/ISSNe:: 1360-9947, 1460-2407
Tipo:: Article
Páginas:: -
DOI:: 10.1093/molehr/gaac035
PubMed:: 36205711
Factor de Impacto:: 1,150 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Henarejos-Castillo, I:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Av Fernando Abril Martorell 106,Torre A,Planta 1a, Valencia 46026, Spain

Univ Valencia, Dept Pediat Obstet & Gynecol, Valencia, Spain
Devesa-Peiro, A.:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Av Fernando Abril Martorell 106,Torre A,Planta 1a, Valencia 46026, Spain

Univ Valencia, Dept Pediat Obstet & Gynecol, Valencia, Spain
de Miguel-Gomez, L.:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Av Fernando Abril Martorell 106,Torre A,Planta 1a, Valencia 46026, Spain
Sebastian-Leon, P.:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Av Fernando Abril Martorell 106,Torre A,Planta 1a, Valencia 46026, Spain
Romeu, M.:: Hosp La Fe, Reprod Med Unit, Valencia, Spain
Aleman, A.:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Av Fernando Abril Martorell 106,Torre A,Planta 1a, Valencia 46026, Spain
Molina-Gil, C.:: Univ Valencia, Dept Pediat Obstet & Gynecol, Valencia, Spain
Pellicer, A.:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Av Fernando Abril Martorell 106,Torre A,Planta 1a, Valencia 46026, Spain

Univ Valencia, Dept Pediat Obstet & Gynecol, Valencia, Spain
Cervello, I:: Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Av Fernando Abril Martorell 106,Torre A,Planta 1a, Valencia 46026, Spain
Diaz-Gimeno, P.:: Instituto de Investigación. (Corresponding Author), IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Av Fernando Abril Martorell 106,Torre A,Planta 1a, Valencia 46026, Spain

Instituto de Investigación. IVI Fdn, Hlth Res Inst La Fe IIS La Fe, Av Fernando Abril Martorell 106,Torre A,Planta 1a, Valencia 46026, Spain

Keywords

infertility; SARS-CoV-2; gene co-expression network; COVID-19 effects; endometrial gene expression; endometrial functions; window of implantation; menstrual cycle; women's reproductive health; virus systemic effects