Maternal sucrose intake during pregnancy alone disrupts testosterone and allopregnanolone levels in the fetal brain of rats

ABSTRACT Background Intake of added sugars, such as sucrose, is high globally. In rats, a maternal high-sucrose diet (HSD) from 10 wk before pregnancy to embryonic day (E)19.5 has widespread impacts on maternal, placental, and fetal blood and brain steroid levels, including glucocorticoids, androgens, and aldosterone. Objective This study examined whether maternal HSD during pregnancy alone is sufficient to alter maternal, placental, and fetal steroids. Methods Pregnant rats received either a control diet (1% kcal sucrose) or an isocaloric, nutrient-matched HSD (26% kcal sucrose) between E0.5-19.5. On E19.5, we collected maternal serum, placenta, fetal blood and brain, and amniotic fluid. We microdissected the placenta and fetal brain and measured 14 steroids using highly sensitive and specific liquid chromatography-tandem mass spectrometry (n=12-15/diet/sex). Results Maternal HSD during pregnancy alone did not alter maternal food intake, maternal body mass, and litter size (all p values ≥ 0.29, Student’s t-test) but increased the percentage of males in a litter (p = 0.03, Student’s t-test). Maternal HSD did not alter steroids in the maternal serum (all p values ≥ 0.21, Student’s t-test), placenta (all p values ≥ 0.07, 2-way analysis of variance (ANOVA)), and fetal blood (all p values ≥ 0.13, 2-way ANOVA). Nonetheless, maternal HSD increased testosterone in the fetal nucleus accumbens (p = 0.04, 2-way ANOVA), decreased allopregnanolone in the fetal amygdala (p = 0.01, 2-way ANOVA), and decreased 11-dehydrocorticosterone in the amniotic fluid (p = 0.05, 2-way ANOVA). Conclusions Maternal HSD during pregnancy alone does not affect steroid levels in the maternal serum, placenta, or fetal blood, but disrupts testosterone and allopregnanolone levels in critical regions of the fetal brain that regulate reward-seeking and emotion. Thus, while a long-term maternal HSD is necessary for widespread endocrine effects, the fetal brain is sensitive to short-term increases in maternal sucrose consumption during pregnancy.