Biology subjects

Yang, X.-r.

Publications and source records attributed to Yang, X.-r..

2 recordsLinked to original sources

bioRxiv2026

Prenatal Dibutyl Phthalate Exposure Dysregulates Fetal-Placental Vascular Function and Placental Vasculature-Specific Lipid Metabolism

IntroductionIn humans, prenatal dibutyl phthalate (DBP) exposure is associated with increased risks of adverse fetal outcomes as well as metabolic and cardiovascular diseases in the offspring in a fetal sex-specific manner. However, mechanisms underlying these prenatal DBP exposure-associated adverse fetal/offspring outcomes are unclear. We hypothesize that environmentally relevant low-dose prenatal DBP exposure dysregulates fetal-placental vascular function and lipid metabolism in a fetal sex-specific manner, thereby impairing placental efficiency and programming adverse offspring metabolic outcomes. MethodsFemale CD-1 adult mice (8-10 weeks) were orally dosed with vehicle or an environmentally relevant low-dose DBP (0.1g/kg/day) daily from 30 days pre-pregnancy through gestational day (GD) 18.5. Fetal-placental vascular hemodynamics of these dams were examined using high-frequency ultrasound at multiple timepoints. The effect of prenatal environmentally relevant low-dose DBP exposure on placental efficiency, spatial transcriptomic profiles, lipid homeostasis, and placental vascular endothelial cells function in male and female fetuses were evaluated at gestational day (GD) 18.5. ResultsThe prenatal low-dose DBP exposure dysregulated the fetal-placental vascular hemodynamic indices from mid-to late gestation. DBP exposure impairs placental efficiency in male, but not female placenta at GD18.5. Further, female placentas exhibited fetal labyrinth vasculature-specific transcriptomic adaptations that preserves placental efficiency and endothelial function. In contrast, male placentas exhibited minimum transcriptomic adaptation, together with compromised placental efficiency and endothelial function associated with lipotoxic lipid profile. ConclusionsIn conclusion, prenatal low-dose DBP exposure dysregulates placental vascular function and lipid homeostasis in a fetal sex-specific manner, with male fetuses being more susceptible to DBP exposure.

physiology↗

bioRxiv2023

MicroRNA-29 Differentially Mediates Preeclampsia-Dysregulated Cellular Responses to Cytokines in Female and Male Fetal Endothelial Cells

IntroductionPreeclampsia (PE) differentially impairs female and male fetal endothelial cell function which is associated with the increased risks of adult-onset cardiovascular disorders in children born to mothers with PE. However, the underlying mechanisms are poorly defined. We hypothesize that dysregulation of microRNA-29a-3p and 29c-3p (miR-29a/c-3p) in PE disturbs gene expression and cellular responses to cytokines in fetal endothelial cells in a fetal sex-dependent manner. MethodsRT-qPCR analysis of miR-29a/c-3p was performed on female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive (NT) and PE pregnancies. Bioinformatic analysis of an RNAseq dataset was performed to identify PE-dysregulated miR-29a/c-3p target genes in female and male P0-HUVECs. Gain- and loss-of-function assays were conducted to determine the effects of miR-29a/c-3p on endothelial monolayer integrity and proliferation in response to TGF{beta}1 and TNF in NT and PE HUVECs at passage 1. ResultsPE downregulated miR-29a/c-3p in male, but not female P0-HUVECs. PE dysregulated significantly more miR-29a/c-3p target genes in female vs. male P0-HUVECs. Many of these PE-differentially dysregulated miR-29a/c-3p target genes are associated with critical cardiovascular diseases and endothelial functions. We further demonstrated that miR-29a/c-3p knockdown specifically recovered the PE-abolished TGF{beta}1-induced strengthening of endothelial monolayer integrity in female HUVECs, while miR-29a/c-3p overexpression specifically enhanced the TNF-promoted cell proliferation in male PE HUVECs. ConclusionsPE differentially dysregulates miR-29a/c-3p and their target genes associated with cardiovascular diseases- and endothelial function in female and male fetal endothelial cells, possibly contributing to the fetal sex-specific endothelial dysfunction observed in PE.

physiology↗