Maternal nutrient restriction and dietary melatonin alter neurotransmitter pathways in placental and fetal tissues

Authors: HARMAN, ALLISON - Mississippi State University; CONTRERAS-CORREA, ZULLY - Mississippi State University; MESSMAN, RILEY - Mississippi State University; SWANSON, REBECCA - Mississippi State University; LEMLEY, CALEB - Mississippi State University

Submitted to: Placenta
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2022
Publication Date: 11/23/2022
Citation: Harman, A.R., Contreras-Correa, Z.E., Messman, R.D., Swanson, R.M., Lemley, C.O. 2022. Maternal nutrient restriction and dietary melatonin alter neurotransmitter pathways in placental and fetal tissues. Placenta. 131:13-22. https://doi.org/10.1016/j.placenta.2022.11.008.
DOI: https://doi.org/10.1016/j.placenta.2022.11.008

Interpretive Summary: Neurotransmitters, such as epinephrine, norepinephrine, dopamine, and serotonin have multiple functions in the body, but generally are responsible for regulating cognitive abilities, mood, and behavior. Recently, the term placental-brain-axis has been used to describe this interconnections of the placenta and brain as they relate to long-term programming effects occurring in utero. Our results describe novel evidence of the presence of neurotransmitters and their synthesis and metabolism in the bovine conceptus. Similar to previous work from our lab, neurotransmitters are greatly influenced by season likely due to their respective abilities to influence circadian information in the brain.

Technical Abstract: Introduction: Recent research indicates an important role in the placental fetal brain axis, with a paucity of information reported in large animals. Melatonin supplementation has been investigated as a potential therapeutic to negate fetal growth restriction. We hypothesized that maternal nutrient restriction and melatonin supplementation would alter neurotransmitter pathways in fetal blood, cotyledonary and hypothalamus tissue. Methods: On day 160 of gestation, Brangus heifers (n = 29 in fall study; n = 25 in summer study) were assigned to one of four 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). Placentomes, fetal blood, and hypothalamic tissue were collected at day 240 of gestation. Neurotransmitters were analyzed in fetal blood and fetal and placental tissues. Transcript abundance of genes in the serotonin pathway and catecholamine pathway were determined in fetal hypothalamus and placental cotyledon. Results: Serotonin was increased (P < 0.05) by 12.5-fold in the blood of fetuses from RES dams versus ADQ in the fall study. Additionally, melatonin supplementation increased (P < 0.05) neurotransmitter metabolites and transcript abundance of the monoamine oxidase A (MAOA) enzyme in the cotyledon. In the summer study, plasma dopamine and placental dopamine receptors were decreased (P < 0.05) in RES dams versus ADQ. Discussion: In conclusion, these data indicate novel evidence of the presence of neurotransmitters and their synthesis and metabolism in the bovine conceptus, which could have greater implications in establishing postnatal behavior.