Establishment of Adenomyosis Organoids as a Preclinical Model to Study Infertility

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 r...

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Published in:Journal of personalized medicine 2022-02, Vol.12 (2), p.219
Main Authors: Juárez-Barber, Elena, Francés-Herrero, Emilio, Corachán, Ana, Vidal, Carmina, Giles, Juan, Alamá, Pilar, Faus, Amparo, Pellicer, Antonio, Cervelló, Irene, Ferrero, Hortensia
Format: Article
Language:English
Subjects:
Biopsy
Cytokeratin
Disease
Drug screening
Endometrium
Enzyme-linked immunosorbent assay
Estrogens
Gene expression
Hormones
Immunofluorescence
Immunohistochemistry
Implantation
Infertility
Laminin
Microenvironments
Molecular modelling
Organoids
Ovaries
Pathogenesis
Patients
Phenotypes
Precision medicine
Pregnancy
Proteins
Smad3 protein
Sox9 protein
Steroids
Tubulin
Ultrasonic imaging
Womens health
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Summary: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 ( = 6) and healthy women ( = 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 (α-tubulin, SOX9, , , , and expression and secretion). Adenomyosis organoids showed higher expression of TGF-β2 and SMAD3 and increased gene expression of , , , and 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.
ISSN:2075-4426
2075-4426
DOI:10.3390/jpm12020219