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Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development.

ABSTRACT: Bariatric surgery is increasingly employed to improve fertility and reduce obesity-related co-morbidities in obese women. Surgical weight loss not only improves the chance of conception but reduces the risk of pregnancy complications including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric procedures increase the incidence of intrauterine growth restriction (IUGR), fetal demise, thromboembolism, and other gestational disorders. Using our rodent model of vertical sleeve gastrectomy (VSG), we tested the hypothesis that VSG in diet-induced, obese dams would cause immune and placental structural abnormalities that may be responsible for fetal demise during pregnancy. VSG dams studied on gestational day (G) 19 had reduced circulating T-cell (CD3+ and CD8+) populations compared with lean or obese controls. Further, local interleukin (IL) 1? and IL 1 receptor antagonist (il1rn) cmRNA were increased in placenta of VSG dams. Placental barrier function was also affected, with increased transplacental permeability to small molecules, increased matrix metalloproteinase 9 expression, and increased apoptosis in VSG. Furthermore, we identified increased placental mTOR signaling that may contribute to preserving the body weight of the fetuses during gestation. These changes occurred in the absence of a macronutrient deficit or gestational hypertension in the VSG dams. In summary, previous VSG in dams may contribute to fetal demise by affecting maternal immune system activity and compromise placental integrity.

SUBMITTER: Spann RA

PROVIDER: S-EPMC5989318 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development.

Spann Redin A RA Lawson William J WJ Bidwell Gene L GL Zamarripa C Austin CA Maranon Rodrigo O RO Bandyopadhyay Sibali S Taylor Erin R ER Reckelhoff Jane F JF Garrett Michael R MR Grayson Bernadette E BE

Clinical science (London, England : 1979) 20180125 2

Bariatric surgery is increasingly employed to improve fertility and reduce obesity-related co-morbidities in obese women. Surgical weight loss not only improves the chance of conception but reduces the risk of pregnancy complications including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric procedures increase the incidence of intrauterine growth restriction (IUGR), fetal demise, thromboembolism, and other gestational disorders. Using our rodent model of vertical sleeve g ...[more]

PMID: 29167317

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Project description:Bariatric surgery is the most effective treatment for obesity and its comorbidities. However, our understanding of the molecular mechanisms behind its beneficial effects is limited. Extracellular vesicles (EVs) comprise an important mode of intercellular communication. They carry nucleic acids, hormones, and signaling molecules and regulate multiple processes. Our aim was to test the role of EVs in the effects of vertical sleeve gastrectomy (VSG) using a mouse model. Small intestinal EVs were obtained from the mice that underwent VSG or control surgery and were on chow or high-fat diet or diet-restricted, and then they were subjected to the proteomic analysis. Enteroid and bacterial cultures were treated with EVs to evaluate their survival effect. A mouse cohort received intraduodenal administration of EVs from VSG or Sham mice for 10 days. Body weight, glucose metabolism, and intestinal morphology were evaluated. EVs were enriched in the intestinal lumen and mucus of VSG compared with Sham mice. Protein composition of VSG and Sham-derived EVs was highly distinct. When introduced into culture, VSG EVs decreased survival of intestinal enteroids and, conversely, promoted proliferation of bacteria. Mice administered with EVs obtained from VSG and Sham groups did not show differences in body weight, food intake, or glucose metabolism. Intestinal morphology was altered, as VSG EVs caused reduction of ileal villi length and decreased epithelial proliferation in the jejunum and ileum. VSG causes remodeling of intestinal EVs, which results in unique protein composition. VSG-derived EVs exhibit cytotoxic effects on epithelial cells and reduce proliferation of intestinal progenitor cells in mice.NEW & NOTEWORTHY This is the first study that investigates the impact of bariatric surgery on protein composition of intestinal extracellular vesicles. Extracellular vesicle composition is greatly altered after vertical sleeve gastrectomy and may potentially modulate various signaling pathways. In our study, extracellular vesicles from vertical sleeve gastrectomy-treated mice promote bacterial proliferation but exhibit cytotoxic effect on epithelial cells and reduce proliferation of intestinal progenitor cells in mice.

Dataset Information

Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development.

Publications

Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development.

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