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.

SSR 2024 Rising Stars #2

Speaker: Dr. Britt Goods, Dartmouth College, USA

Title: Using single-cell transcriptomics to understand ovulation and drive contraceptive discovery

Description: Single-cell methods have revolutionized our ability to understand complex processes. My research leverages these methods, including single-cell RNA-sequencing, to better understand ovulation and inform drug discovery. Here, I will discuss some recent work we have performed to understand factors that drive ovulation over time with spatial transcriptomics datasets and how we have used this, plus data integration methods, to nominate novel drug targets.

Speaker: Dr. Azusa Inoue, RIKEN, Yokohama, Japan

Title: Genomic imprinting mediated by maternal histone modifications

SSR 2024 Rising Stars #1

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.

Placental strategies supporting fetal growth during normal and suboptimal gestational environments

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.

Storing Sugar in the Uterus: Glycogen Metabolism during Early Pregnancy

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.

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.

Kisspeptin neurons and the circuits that control ovulation

In females, the mid-cycle surge in gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion triggers ovulation. This neuroendocrine process is mediated by a population of neurons in the preoptic area that produce the neuropeptide kisspeptin and drive the activity of GnRH neurons for the surge. In female rodents, and possibly in other species, the preovulatory surge is timed to precede the onset of activity to ensure that ovulation coincides with sexual behavior. In this presentation, I will focus on the regulation of preoptic area kisspeptin neuron activity by the central circadian clock.

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