Speaker: Dr. Amanda Patterson, University of Missouri School of Medicine
Title: Towards understanding mesenchymal-epithelial transition in endometrial epithelial regeneration.
Description: Mesenchymal-epithelial transition (MET) is critical for fetal tissue and organ development and is exploited by pathologies such as cancer and fibrosis. The uterus uses this mechanism in adults under non-pathological conditions to regenerate the endometrial epithelium following parturition and in menstruation-like conditions in mice. During this webinar, I will discuss the advances made in understanding MET in normal physiological regeneration events to gain insight into its role in pathologies when dysregulated.
Speaker: Dr. Xiaoqiu (Churchill) Wang, North Carolina State University
Title: Decoding molecular mechanisms controlling uterine aging.
Description: Advanced maternal age (i.e., ≥35 years old) is associated with an increased risk of adverse pregnancy outcomes such as infertility, preterm birth, intrauterine growth restriction, congenital heart disease and other fetal abnormalities. Much attention has been focused on ovarian function and oocyte quality (“the Seed”); but we provide evidence that defects in uterine decidualization (a process of uterine stroma cell proliferation and differentiation to accommodate implanting embryo; “the Soil”) could be a major cause of age-related reproductive decline in mice, which, in turn, interferes with the establishment of a functional feto-maternal exchange unit. In this talk, I will discuss our recent efforts on elucidating the mechanisms underlying reproductive aging in the uterus, particularly the convergence of the Sirtuin 1 (SIRT1) signaling pathway and the hormonal endometrial response during endometrial decidualization.
Speaker: Dr. Katy Patras, Baylor College of Medicine, USA
Title: Gestational diabetes disrupts maternal immunity and the vaginal microbiota to promote bacterial infection.
Description: Group B Streptococcus (GBS) is a pervasive perinatal pathogen, and gestational diabetes mellitus (GDM) increases the risk of GBS perinatal disease although the underlying mechanisms are unknown. Using a novel murine GDM model of GBS colonization, we found that GDM mice had greater GBS dissemination and worse neonatal outcomes. GDM altered host responses, including reduced uterine natural killer cell activation and recruitment, and distinct vaginal microbial taxa were associated with GDM status and GBS invasive disease status. Our translational model of GBS perinatal transmission in GDM hosts recapitulates several clinical aspects and enables discovery of host and bacterial drivers of GBS perinatal disease.
Speaker: Dr. Daniel Mathew, University of Tennessee, USA
Title: The In Vitro Produced Conceptus: What the Endometrium Can Tell Us
Description: The early conceptus creates a microenvironment with the surrounding endometrium, supporting pre-implantation development. During this webinar I’ll discuss how the in vitro produced cow conceptus impacts the endometrial transcriptome and surrounding proteome compared to the in vivo derived conceptus and how that may influence establishment of pregnancy.
The placenta is essential for mammalian development and a key determinant of life-long offspring health. It is responsible for transporting all the nutrients and oxygen a fetus needs to develop and grow and secretes hormones that adapt maternal physiology to support the pregnancy. However, the placenta is not a static organ. In this talk I will present our work undertaken in experimental models showing that placental formation and function adapts developmentally to the needs of the growing fetus during normal gestation, as well as in response to suboptimal gestational environments, namely obesity and hypoxia. Impairments in placental formation and function have consequences for fetal growth and birthweight, which in turn, dictate perinatal survival and risk of non-communicable diseases in later postnatal life. Thus, identifying how the placenta responds and adapts to developmental and environmental cues may be informative for the design of strategies to optimise pregnancy and long-term health outcomes.
The endometrium needs to regulate glucose availability precisely; too much or too little impairs decidualization and embryo development. We have shown that the epithelium and decidua store distinct pools of glucose as glycogen during early pregnancy. Thus, glycogen may represent a vital way to buffer glucose concentrations before and during implantation.
Although much is known about the molecular signaling during implantation, the uterine 3D architecture that facilitates embryo development remains unknown. Imaging the mouse embryo and the uterine milieu simultaneously we uncovered patterns of embryo movement and dynamic shape changes in the uterine lumen and glands in preparation for implantation. When applied to mouse mutants with known implantation defects, this method detected striking peri-implantation abnormalities in uterine morphology that cannot be visualized by histology. Analyzing the uterine and embryo structure in 3D for genetic mutants, hormonal perturbations and pregnancies treated with pathway inhibitors is helping us uncover novel molecular pathways and global structural changes that contribute to successful implantation of an embryo. Our studies have implications for understanding how structure-based embryo-uterine communication is key to determining an optimal implantation site, which is necessary for the success of a pregnancy.
