Biology subjects

Megli, C. J.

Publications and source records attributed to Megli, C. J..

3 recordsLinked to original sources

bioRxiv2024

Toxoplasma gondii infection misdirects placental trophoblast lineage specification

Pregnancy is a critical point of vulnerability to infection and other insults that could compromise proper fetal development. The placenta acts as a protective and nutrient-permeable barrier to most infectious agents, but a few are capable of bypassing its defenses. Remarkably little is known about how exposure to these select pathogens might impact ongoing placental development. Here we demonstrate that Toxoplasma gondii entirely misdirects the developmental program of trophoblast stem cells. Infection of progenitor cytotrophoblasts prevents fusion and differentiation to infection-resistant syncytiotrophoblast. Rather, T. gondii elicits a unique transcriptional identity that polarizes cytotrophoblasts to the infection-permissive extravillous trophoblast fate. Strong evidence of developmental disruption is found in multiple orthogonal models, including trophoblast stem cells, trophoblast organoids, and chorionic villi. Manipulation of cell fate by the parasite is most dramatic in trophoblast organoids, where we see robust outgrowth of HLA-G(+) extravillous trophoblasts. Collectively, these data show that Toxoplasma antagonizes differentiation of an infection-resistant cell type by inducing formation of an infection-permissive cell type, therefore potentiating its own transmission to the fetus.

developmental biology↗

bioRxiv2024

Scoping Review of Maternal Monocytes and the Syncytiotrophoblast: Bi-Directional Communication in the Intervillous Space

The relationship between maternal monocytes and the placenta is crucial for successful pregnancy. As existing reviews focus on the research on decidual macrophages or Hofbauer cells (fetal macrophages), we conducted a scoping review of literature studies examining the relationship between circulating maternal monocytes and the villous trophoblast. The goal of this review was to outline existing research within the field, disseminate further information, and to identify current knowledge gaps within the field. We searched the PubMed (MEDLINE) database for relevant articles published since 1995 that studied human tissue or cell lines. Our results showed clear trends in the type of monocyte and placental primary tissues and cell lines used. Further classification of these articles revealed four primary categories of monocyte-trophoblast interaction research: monocyte presence or recruitment to the placenta, monocyte phenotype in the intervillous space, monocyte-placental adhesion, and monocyte interaction with syncytiotrophoblast-derived extracellular vesicles (STBEVs). Although limited in scope and number, these studies implicate the importance of monocyte-trophoblast interactions, and their significant roles in maternal disease.

immunology↗

bioRxiv2023

Diet influences community dynamics following vaginal group B Streptococcus colonization

The vaginal microbiota plays a pivotal role in reproductive, sexual, and perinatal health and disease. Unlike the well-established connections between diet, metabolism, and the intestinal microbiota, parallel mechanisms influencing the vaginal microbiota and pathogen colonization remain overlooked. In this study, we combine a mouse model of Streptococcus agalactiae strain COH1 (GBS) vaginal colonization with a mouse model of pubertal-onset obesity to assess diet as a determinant of vaginal microbiota composition and its role in colonization resistance. We leveraged culture-dependent assessment of GBS clearance and culture-independent, sequencing-based reconstruction of the vaginal microbiota in relation to diet, obesity, glucose tolerance, and microbial dynamics across time scales. Our findings demonstrate that excessive body weight gain and glucose intolerance are not associated with vaginal GBS density or timing of clearance. Diets high in fat and low in soluble fiber are associated with vaginal GBS persistence, and changes in vaginal microbiota structure and composition due to diet contribute to GBS clearance patterns in nonpregnant mice. These findings underscore a critical need for studies on diet as a key determinant of vaginal microbiota composition and its relevance to reproductive and perinatal outcomes. IMPORTANCEThis work sheds light on diet as a key determinant influencing the composition of vaginal microbiota and its involvement in group B Streptococcus (GBS) colonization in a mouse model. The study shows that dietary components, such as dietary fat and soluble fiber, impact GBS density and timing of clearance in the female reproductive tract. These findings are particularly significant given clear links between GBS and adverse reproductive and neonatal outcomes, advancing our understanding by identifying critical connections between dietary components, factors originating from the intestinal tract, vaginal microbiota, and reproductive outcomes.

microbiology↗