A maternal high-fat, high-sucrose diet has sex-specific effects on fetal glucocorticoids with little consequence for offspring metabolism and voluntary locomotor activity in mice.

Eunice H Chin,Kiran K Soma,Kaitlyn M Martel,William T Gibson,Jordan E Hamden,Kim L Schmidt,Chi Kin Wong,Julian K Christians,Colette Kanellopoulos-Langevin

doi:10.1371/journal.pone.0174030

Eunice H Chin, Kiran K Soma + Show 7 more

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https://doi.org/10.1371/journal.pone.0174030

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Abstract

Maternal overnutrition and obesity during pregnancy can have long-term effects on offspring physiology and behaviour. These developmental programming effects may be mediated by fetal exposure to glucocorticoids, which is regulated in part by placental 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and 2. We tested whether a maternal high-fat, high-sucrose diet would alter expression of placental 11β-HSD1 and 2, thereby increasing fetal exposure to maternal glucocorticoids, with downstream effects on offspring physiology and behaviour. C57BL/6J mice were fed a high-fat, high-sucrose (HFHS) diet or a nutrient-matched low-fat, no-sucrose control diet prior to and during pregnancy and lactation. At day 17 of gestation, HFHS dams had ~20% lower circulating corticosterone levels than controls. Furthermore, there was a significant interaction between maternal diet and fetal sex for circulating corticosterone levels in the fetuses, whereby HFHS males tended to have higher corticosterone than control males, with no effect in female fetuses. However, placental 11β-HSD1 or 11β-HSD2 expression did not differ between diets or show an interaction between diet and sex. To assess potential long-term consequences of this sex-specific effect on fetal corticosterone, we studied locomotor activity and metabolic traits in adult offspring. Despite a sex-specific effect of maternal diet on fetal glucocorticoids, there was little evidence of sex-specific effects on offspring physiology or behaviour, although HFHS offspring of both sexes had higher circulating corticosterone at 9 weeks of age. Our results suggest the existence of as yet unknown mechanisms that mitigate the effects of altered glucocorticoid exposure early in development, making offspring resilient to the potentially negative effects of a HFHS maternal diet.

Highlights

Adult physiology and behaviour are influenced by early life environment, including maternal diet and stress during pregnancy [1,2,3,4,5]
Among females paired with males for only one night, such that the timing of pregnancy was known, HFHS females weighed more at the beginning of pregnancy (F1,22 = 6.37, P = 0.02; Fig 1B), but control diet (CON) females tended to gain more weight between pairing and day 17 of gestation (F1,21 = 3.11, P = 0.09, controlling for number of conceptuses, F1,21 = 21.33, P < 0.0001)
HFHS females euthanized at day 17 of gestation had greater fat mass, but not greater lean mass, than CON females, as measured by quantitative magnetic resonance (QMR) (Table 2)

Summary

Introduction

Adult physiology and behaviour are influenced by early life environment, including maternal diet and stress during pregnancy [1,2,3,4,5]. The transfer of glucocorticoids from maternal to fetal circulation is regulated in part by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) [13] This enzyme, which is highly expressed in the placenta, inactivates glucocorticoids into metabolites (corticosterone to 11-dehydrocorticosterone in rodents and cortisol to cortisone in humans) that have lower affinity for their cognate receptors [13]. Maternal stress generally reduces placental 11β-HSD2 activity [5,18,19], some studies have found the opposite pattern [5]. The effects of maternal overnutrition and/or obesity on placental 11β-HSD2 activity have received less study [20], a high-fat diet decreases placental 11β-HSD2 expression and enzymatic activity in mice [21,22]

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