SSR 2024 Rising Stars #4

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.

Development of a new non-hormonal contraceptive targeting the AMH/AMHR2 axis in females.

Speaker: Dr. David Pépin, Harvard Medical School

Title: Development of a new non-hormonal contraceptive targeting the AMH/AMHR2 axis in females.

Description: Anti-Müllerian hormone (AMH) is a paracrine factor produced by growing follicles that mediates negative feedback on the activation and growth of new pre-antral follicles. Sustained supraphysiological AMH can suppress follicular development and induce contraception. Herein we will present findings on the mechanism of action of AMH in follicles, the development of new contraceptive modalities including gene therapy with AMH and small molecule agonists of the AMH receptor (AMHR2), and their evaluation in several animal models from mice to cats.

Illuminating the (uterine) path: from embryo movement to 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.

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