O-093 Endometrium-blastocyst cross talk: how far are we from understanding?

Abstract The early events characterising implantation of the human embryo represent a critical step in which proper activation orchestrated molecular pathways regulate success pregnancy. Understanding this complex network is considered by many last frontier reproduction. Although outstanding research advancements have provided clinicians tools to select best quality embryo, identification optimal timing endometrium ready accommodate it remains challenge. Over decade several studies identified key players involved preparation and diffusible signals guiding its journey toward maternal endometrial tissue been uncovered (Massimiani et al. 2020). However, pieces puzzle are still missing. For convenience, process subdivided into sequential processes, completion one being propaedeutic following. Once blastocyst has arrived close proximity uterine epithelium, first event occurring escape from zona pellucida. basis hatching poorly understood, species-specific differences reported. Using mouse model, we recently demonstrated that thyroid hormone up-regulates expression specific lytic enzymes (Isp1 Isp2) known mediators lysis. Interestingly, observed TH-mediated upregulation Isp1 Isp2 strictly dependent on presence stromal cell feeder layer, clearly indicating blastocyst–endometrium interaction indispensable for increased these proteases. So far, no regulating humans identified, only mechanical forces proposed induce opening; however very possibility proteases may be also suggested (Almagor al., 2020), although further needed support hypothesis. free zona, contacts epithelium starts proceed consolidation Hormones, pro- anti-inflammatory mediators, growth factors their receptors, adhesion molecules, protease inhibitors reported regulation apposition, adhesion, invasion Among signals, Notch pathway recognized embryo-endometrium cross talk (Cuman 2014). Transient Notch1 receptor decidualization (Afshar 2012), limiting implantation, blastocyst-conditioned medium shown family members decidual cells (Hess 2007). Expression notch receptors ligands trophectoderm as well We previously secreted factor epidermal factor-like domain 7 (EGFL7) novel modulator pathway, expressed trophoblast (Fitch 2004; Lacko 2014) regulates migration ability activating 2015). Data will presented demonstrating EGFL7 mainly localized glandular throughout menstrual cycle. significantly upregulated whole during secretory phase, particularly compartment; observation supported vitro showing decidualized cells, suggesting role implantation. Further evidence levels strongly downregulated women with impaired fertility. propose player talk.