Altered hormone receptor expression in rat placenta following maternal vertical sleeve gastrectomy

Abstract

Intrauterine growth restriction (IUGR) results in long term metabolic disease later in life. Our previous work using vertical sleeve gastrectomy (VSG) to surgically reduce maternal obesity prior to pregnancy results in small‐for‐gestational age offspring that develop greater metabolic disease later in life compared to obese controls. The mechanism driving this transmission of metabolic disease following bariatric surgery from mother to offspring is undetermined.VSG in humans and rodents results in elevated bile acids and glucagon like peptide‐1 and reduced ghrelin amongst a variety of other circulating hormone changes. Independent lines of research have been undertaken to determine whether these hormone changes are independently sufficient to elicit the improvements identified following surgical weight loss. Though these hormone changes are potentially beneficial in the non‐pregnant setting, in the context of pregnancy these types of hormone changes collectively may adversely affect placental development and fetal health. The present work seeks to identify if the hormone changes following VSG are sensed by the late stage placenta.Here we performed VSG or Sham‐VSG in female Long Evans rats and after 5 weeks recovery, we time‐mated them. At gestational day 19, animals were euthanized. Pregnant VSG rats exhibited elevations in plasma levels of bile acids, GLP1 and testosterone and reductions in ghrelin and leptin in comparison to controls. Placenta were also excised and processed for real‐time PCR‐based gene expression analysis. When compared to placenta from lean, body‐weight matched control dams, VSG placenta exhibited reduced mRNA expression of insulin receptors (ir), leptin receptors (obr), androgen receptors (ar) and bile salt export pump (abcb1). Furthermore, VSG placenta expressed significantly increased ghrelin O‐acyltransferase (goat) mRNA, the rate limiting enzyme for production of active ghrelin. No differences were identified in ghrelin receptor (ghsr) and glucagon‐like peptide 1 receptor (glpr).Taken together, these preliminary data suggest that during VSG pregnancy, the fetal‐placental unit responds to the altered hormonal milieu of the dam. Further work is required to determine the role of these particular hormones in the growth and development of the fetus and whether they contribute to the long‐term outcomes of VSG offspring.Support or Funding InformationThis work is partially supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20 GM104357, and the Mississippi Center of Excellence in Perinatal Research COBRE (P20 GM121334).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.