Gestational testosterone excess early to mid-pregnancy disrupts maternal lipid homeostasis and activates biosynthesis of phosphoinositides and phosphatidylethanolamines in sheep

Autor: Nadia Saadat, Brooke Pallas, Joseph Ciarelli, Arpita Kalla Vyas, Vasantha Padmanabhan
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-56886-6
Popis: Abstract Gestational hyperandrogenism is a risk factor for adverse maternal and offspring outcomes with effects likely mediated in part via disruptions in maternal lipid homeostasis. Using a translationally relevant sheep model of gestational testosterone (T) excess that manifests maternal hyperinsulinemia, intrauterine growth restriction (IUGR), and adverse offspring cardiometabolic outcomes, we tested if gestational T excess disrupts maternal lipidome. Dimensionality reduction models following shotgun lipidomics of gestational day 127.1 ± 5.3 (term 147 days) plasma revealed clear differences between control and T-treated sheep. Lipid signatures of gestational T-treated sheep included higher phosphoinositides (PI 36:2, 39:4) and lower acylcarnitines (CAR 16:0, 18:0, 18:1), phosphatidylcholines (PC 38:4, 40:5) and fatty acids (linoleic, arachidonic, Oleic). Gestational T excess activated phosphatidylethanolamines (PE) and PI biosynthesis. The reduction in key fatty acids may underlie IUGR and activated PI for the maternal hyperinsulinemia evidenced in this model. Maternal circulatory lipids contributing to adverse cardiometabolic outcomes are modifiable by dietary interventions.
Databáze: Directory of Open Access Journals
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