02145nas a2200349   4500000000100000000000100001008004100002260001500043653002100058653002600079653002400105653002500129653002600154100001300180700001700193700001500210700002200225700001700247700001900264700001600283700001700299700001700316700001700333700001700350700001300367700002400380245013200404856009600536490000700632520114200639022001401781       2022                            d  c2022-12-1410aApical secretion10aEndometrial organoids10aInfertile organoids10aIntra-organoid fluid10ablastocyst attachment1 aWei Zhou1 aSiena Barton1 aJinwei Cui1 aLeilani L. Santos1 aGuannan Yang1 aCatharyn Stern1 aViolet Kieu1 aWan Tinn Teh1 aCatarina Ang1 aTarana Lucky1 aJoseph Sgroi1 aLouie Ye1 aEvdokia Dimitriadis00aInfertile human endometrial organoid apical protein secretions are dysregulated and impair trophoblast progenitor cell adhesion  uhttps://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1067648/full0 v133 aEmbryo implantation failure leads to infertility. As an important approach to regulate implantation, endometrial epithelial cells produce and secrete factors apically into the uterine cavity in the receptive phase to prepare the initial blastocyst adhesion and implantation. We established organoids using endometrial biopsies from women with normal fertility and primary infertility and treated them with hormones to model the receptive phase endometrial epithelium. Our data show that infertile organoids were dysregulated in their response to estrogen and progesterone treatment. Proteomic analysis of organoid apical secretions identified 150 dysregulated proteins between fertile and infertile groups (>1.5-fold change). Trophoblast progenitor spheroids (blastocyst surrogates) treated with infertile organoid apical secretions significantly compromised their adhesion to organoid epithelial cell monolayers compared to fertile group (P < 0.0001). Overall, this study paves the way to determine the molecular mechanisms by which endometrial epithelial apical released factors regulate blastocyst initial attachment and implantation.  a1664-2392