02490nas a2200337   4500000000100000000000100001008004100002260001100043653001600054653002800070653001600098653001400114653002200128653002600150100002500176700002800201700001800229700001800247700001500265700001700280700001600297700002100313700002000334700002200354245008700376856004400463300000800507490000700515520161600522022001402138       2022                            d  c2022/210aadenomyosis10agestational endometrium10ainfertility10aorganoids10apreclinical model10asecretory endometrium1 aElena Juárez-Barber1 aEmilio Francés-Herrero1 aAna Corachán1 aCarmina Vidal1 aJuan Giles1 aPilar Alamá1 aAmparo Faus1 aAntonio Pellicer1 aIrene Cervelló1 aHortensia Ferrero00aEstablishment of Adenomyosis Organoids as a Preclinical Model to Study Infertility  uhttps://www.mdpi.com/2075-4426/12/2/219  a2190 v123 aAdenomyosis 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 (α-tubulin, SOX9, SPP1, PAEP, LIF, and 17βHSD2 expression and SPP1 secretion). Adenomyosis organoids showed higher expression of TGF-β2 and SMAD3 and increased gene expression of SPP1, PAEP, LIF, and 17βHSD2 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.  a2075-4426