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

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.

Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta‐analysis of animal studies

“…Birth weight was obtained from N = 63 studies ( N = 6530 offspring), one study was included twice in meta‐analysis since they reported on two separate cohorts . In six studies, data on birth weight was not extractable .…”

“…Sixty‐eight studies, including N = 1980 animals, reported on offspring's glucose levels at birth until 12 months of age. One study was included twice in the meta‐analysis since they reported on two different cohorts . In five studies, we were unable to extract outcome data .…”

“…Birth weight was obtained from N = 63 studies (N = 6530 offspring), one study was included twice in meta-analysis since they reported on two separate cohorts. 25 In six studies, data on birth weight was not extractable. [26][27][28][29][30][31] There was no difference in birth weight between offspring of mothers with obesity and offspring of mothers with a normal weight, SMD −0.05 [95% CI −0.17; 0.07], I 2 = 74% (figure S1).…”

“…Body weight of offspring was obtained from N = 123 studies (N = 5772 offspring), two studies were included twice in the metaanalysis since they reported on two separate cohorts. 25,32 Body weight was measured at age 4 days up to 13 months. We were unable to extract outcome data from four studies.…”

High sucrose low copper diet in pregnant diabetic rats induces transient oxidative stress, hypoxia, and apoptosis in the offspring's liver

“…Previous studies by us and by others (Chin et al, ; Weksler‐Zangen et al, ) showed that rat pups weight did not vary between the genders up to PND 21. Hence, we did not discriminate between genders before weaning.…”