Abstract
Abstract The placenta modulates fetal brain development in mice and humans, with a paucity of information reported in cattle. The objective was to determine the effects of maternal nutrient restriction and melatonin supplementation on neurotransmitter concentrations in the cotyledon, fetal hypothalamus, and fetal blood. At day 160 of gestation, 29 spring-calving and 25 fall-calving Brangus heifers were assigned treatments: adequately fed (ADQ-CON; 100% NRC recommendation), nutrient restricted (RES-CON; 60% NRC recommendation), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL; RES-MEL). Fetuses were removed at day 240 of gestation for collection of placentomes, blood, and hypothalamic tissue. Neurotransmitters (serotonin, 5-HT; dopamine, DA; norepinephrine, NE; epinephrine, EPI) and metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; 5-hydroxyindoleacetic acid, 5-HIAA; homovanillic acid HVA) were analyzed by LCMS or HPLC in blood or tissues, respectively. Data were analyzed by ANOVA using the mixed procedure in SAS with seasons analyzed separately. In spring-calving heifers, melatonin increased (P ≤ 0.05) concentrations of DOPAC, DA, 5-HIAA, and HVA in the cotyledon. Nutrient restriction and melatonin supplementation increased (P ≤ 0.05) blood 5-HT. In both calving seasons, there was a nutrition by treatment interaction in hypothalamic 5-HT (P ≤ 0.01), whereby RES-MEL was increased compared with ADQ-MEL. For fall-calving heifers, no differences were observed in neurotransmitter concentrations in the cotyledon. Hypothalamic NE was increased (P = 0.02) in RES vs. ADQ, while hypothalamic and blood DA were decreased (P ≤ 0.05) in RES vs. ADQ. Hypothalamic 5-HIAA was increased (P = 0.05) in the MEL vs. CON, while blood EPI was decreased (P = 0.04) in MEL vs. CON. In summary, nutrient restriction and melatonin supplementation alter concentrations of neurotransmitters and their metabolites in a seasonally dependent manner. Further investigation into the gene expression of these neurotransmitter pathways is necessary to better define the bovine placental-brain axis.
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