Effects of stress during pregnancy on hepatic glucogenic capacity in rat dams and their fetuses.

Kathryn L Franko,Alison J Forhead,Abigail L Fowden

doi:10.14814/phy2.13293

Abstract

Stress during pregnancy is associated with metabolic dysfunction in the adult offspring in human and other animals. However, little is known about the metabolic effects of pregnancy stress on the mothers and fetuses during pregnancy itself. This study aimed to determine the consequences of the common experimental procedures of injection and single housing in pregnant rats on fetal and maternal hepatic glucogenic capacities. On day (D) 20 of pregnancy, feto‐placental weights and the glycogen content and activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose‐6‐phosphatase (G6Pase) of fetal and maternal liver were measured in rats pair or single housed from D1 with or without saline injection from D15 to D19. Housing and saline injection both affected hepatic glucogenic capacity. In maternal liver, saline injection but not housing reduced glycogen content and raised G6Pase activity, whereas housing but not treatment increased PEPCK activity. In fetuses, housing and injection interacted in regulating PEPCK activity and reducing hepatic glycogen content and placental weight. Body weight was decreased and hepatic G6Pase increased by injection but not housing in the fetuses. Single‐housed dams ate less than those pair‐housed near term while saline injection elevated maternal plasma corticosterone concentrations. Thus, single housing and saline injection are both stresses during rat pregnancy that alter feto‐placental weight and hepatic glucogenic capacity of the fetuses and dams near term. Routine experimental procedures per se may, therefore, have consequences for offspring hepatic phenotype as well as modifying the outcomes of dietary and other environmental challenges during pregnancy.

Highlights

Human epidemiological studies have shown that stress during pregnancy is often associated with low birth weight and an increased risk of adult-onset and other diseases, such as glucose intolerance, Type 2 diabetes, asthma, hypertension, and behavioral disorders (Barker 1994; Martin-Gronert and Ozanne 2012; Hanson and Gluckman 2014; Mina and Reynolds 2014; Vaiserman 2015; Andersson et al 2016)
The results demonstrate that both single housing and saline injection of pregnant rats alter the hepatic glucogenic capacity of maternal and fetal liver near term
The changes in hepatic glucogenic capacity were accompanied by reduced food intake in late gestation during single housing and by increased corticosterone concentrations in saline-injected dams

Summary

Introduction

Human epidemiological studies have shown that stress during pregnancy is often associated with low birth weight and an increased risk of adult-onset and other diseases, such as glucose intolerance, Type 2 diabetes, asthma, hypertension, and behavioral disorders (Barker 1994; Martin-Gronert and Ozanne 2012; Hanson and Gluckman 2014; Mina and Reynolds 2014; Vaiserman 2015; Andersson et al 2016). Maternal restraint, dietary manipulation, and direct glucocorticoid administration have all been shown to cause postnatal abnormalities in hepatic glucose metabolism in the offspring consistent with the human epidemiological data (McMillen and Robinson 2005; Martin-Gronert and Ozanne 2012; Mina and Reynolds 2014). Rats exposed in utero to these stresses are glucose intolerant with increased hepatic gluconeogenic enzyme activities and abnormal responses to glucoregulatory hormones as adults (Burns et al 1997; Desai et al 1997; Nyirenda et al 1998; Lesage et al 2004; D’Mello and Liu 2006; Franko et al 2010).

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