Establishment of Adenomyosis Organoids as a Preclinical Model to Study Infertility.

Data de publicació: 04/02/2022 Data Ahead of Print: 04/02/2022

Autors de IIS La Fe

Autors aliens a IIS La Fe

Vidal, Carmina
Giles, Juan
Alama, Pilar

Grups d'Investigació

Biología Reproductiva y Bioingeniería en Reproducción Humana

Leader

Nicolás Garrido Puchalt
Medicina Reproductiva

Investigador Principal

José Morales Roselló

Abstract

Adenomyosis is related to infertility and miscarriages, but so far there are no robust in vitro models that reproduce its pathological features to study the molecular mechanisms involved in this disease. Endometrial organoids are in vitro 3D models that recapitulate the native microenvironment and reproduce tissue characteristics that would allow the study of adenomyosis pathogenesis and related infertility disorders. In our study, human endometrial biopsies from adenomyosis (n = 6) and healthy women (n = 6) were recruited. Organoids were established and hormonally differentiated to recapitulate midsecretory and gestational endometrial phases. Physiological and pathological characteristics were evaluated by immunohistochemistry, immunofluorescence, qRT-PCR, and ELISA. Secretory and gestational organoids recapitulated in vivo glandular epithelial phenotype (pan-cytokeratin, Muc-1, PAS, Laminin, and Ki67) and secretory and gestational features (a-tubulin, SOX9, SPP1, PAEP, LIF, and 17ßHSD2 expression and SPP1 secretion). Adenomyosis organoids showed higher expression of TGF-ß2 and SMAD3 and increased gene expression of SPP1, PAEP, LIF, and 17ßHSD2 compared with control organoids. Our results demonstrate that organoids derived from endometria of adenomyosis patients and differentiated to secretory and gestational phases recapitulate native endometrial-tissue-specific features and disease-specific traits. Adenomyosis-derived organoids are a promising in vitro preclinical model to study impaired implantation and pregnancy disorders in adenomyosis and enable personalized drug screening.

Dades de la publicació

ISSN/ISSNe:: 2075-4426, 2075-4426
Tipus:: Article
Pàgines:: -
DOI:: 10.3390/jpm12020219
PubMed:: 35207707
Factor d'Impacte:: 0,757 SCImago ℠
Quartil:: Q2 SCImago ℠

Documents

No hi ha documents

Mètriques

Filiacions

Juarez-Barber, Elena:: Instituto de Investigación. Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Instituto de Investigación. Inst Invest Sanitaria La Fe, Fdn IVI, Valencia 46026, Spain
Frances-Herrero, Emilio:: Instituto de Investigación. Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, 46010 Valencia, Spain

Instituto de Investigación. Inst Invest Sanitaria La Fe, Fdn IVI, Valencia 46026, Spain

Univ Valencia, Dept Pediat Obstet & Ginecol, Valencia 46010, Spain
Corachan, Ana:: Instituto de Investigación. Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, 46010 Valencia, Spain

Instituto de Investigación. Inst Invest Sanitaria La Fe, Fdn IVI, Valencia 46026, Spain

Univ Valencia, Dept Pediat Obstet & Ginecol, Valencia 46010, Spain
Vidal, Carmina:: Departament of Gynecology, IVIRMA-Valencia, 46015 Valencia, Spain

IVIRMA Valencia, Dept Gynecol, Valencia 46015, Spain
Giles, Juan:: Departament of Gynecology, IVIRMA-Valencia, 46015 Valencia, Spain

IVIRMA Valencia, Dept Gynecol, Valencia 46015, Spain
Alama, Pilar:: Departament of Gynecology, IVIRMA-Valencia, 46015 Valencia, Spain

IVIRMA Valencia, Dept Gynecol, Valencia 46015, Spain
Faus, Amparo:: Instituto de Investigación. Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Instituto de Investigación. Inst Invest Sanitaria La Fe, Fdn IVI, Valencia 46026, Spain
Pellicer, Antonio:: Instituto de Investigación. Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Departament of Gynecology, IVIRMA-Rome, 00197 Rome, Italy

Instituto de Investigación. Inst Invest Sanitaria La Fe, Fdn IVI, Valencia 46026, Spain

IVIRMA Rome, Dept Gynecol, I-00197 Rome, Italy
Cervello, Irene:: Instituto de Investigación. Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Instituto de Investigación. Inst Invest Sanitaria La Fe, Fdn IVI, Valencia 46026, Spain
Ferrero, Hortensia:: Instituto de Investigación. Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Instituto de Investigación. Inst Invest Sanitaria La Fe, Fdn IVI, Valencia 46026, Spain