Abstract: Early human placental and embryonic development occurs in a physiologically low oxygen environment. A responsive endometrium creates a microenvironment essential for implantation of the conceptus and placentation. Uterine glands are the source of histotrophic nutrition for the conceptus before the definitive haemochorial placenta is established. Dysregulated endometrial maturation is implicated as the cause of many adverse pregnancy outcomes, including recurrent implantation failure, miscarriage, pre-eclampsia and intrauterine growth restriction. There have been many technological developments in recent years which have generated excellent models of the endometrial and placental function, and my research is at the forefront of some of these advances. My pilot data provide evidence of increased cellular stress in endometrial glands of patients who later suffered early pregnancy losses (EPL). Interestingly, gland organoids derived from these biopsies retain characteristics of the original tissues, exhibiting increased cellular stress and lower proliferation rates, compared to organoids derived from patients who went on to have a successful pregnancy. Endometrial cellular stress can be reduced and organoid formation efficiency increased by treating EPL organoids with certain anti-diabetic or lipid-lowering drugs known to reduce cellular stress. I further demonstrated that gland organoids can be derived from menstrual flow. This technique has wide-ranging impact for non-invasive investigation and personalised approaches to treatment of common gynaecological conditions, such as endometriosis, and reproductive disorders, including failed implantation after IVF and recurrent miscarriage.

Biography: Tereza Cindrova-Davies received her MPhil and PhD from the University of Cambridge. Tereza worked as a research fellow at the University of Cambridge between 2003-2022, and currently holds a lectureship at the Queen Mary University of London. Tereza has been awarded international prizes for her research, including the Elsevier Science New Investigator Award at the IFPA meeting in Glasgow in 2005, and the Gabor Than award for ‘outstanding contributions to the field of placentology in all its aspects’, at the IFPA meeting in Graz in 2008. Tereza’s research has embraced the role of oxidative stress in normal and pathological pregnancies, placental senescence and H2S in pregnancy pathologies. Early pregnancy is a key area of Tereza’s current research interests. Her recent research concentrates on investigating early placental development, the role of the human yolk sac and histotrophic nutrition. Tereza has been instrumental in developing human and mouse organoid cultures, and used these to investigate the function of the endometrial glands in early pregnancy. In addition, she recently succeeded in deriving physiologically relevant endometrial organoid cultures non-invasively from menstrual flow. Her future research is directed to explore why the majority of human pregnancies fail, either before implantation or as a result of early pregnancy loss.