Mounting evidence in the literature indicates an important role of endogenous and exogenous melatonin in driving physiological and molecular adaptations in livestock. Melatonin has been extensively studied in seasonally polyestrous animals whereby supplementation studies have been used to adjust circannual rhythms in herds of animals under abnormal photoperiodic conditions. Livestock undergo multiple metabolic and physiological adaptation processes throughout their production cycle which can result in decreased immune response leading to chronic illness, weight loss, or decreased production efficiency; however, melatonin’s antioxidant capacity and immunostimulatory properties could alleviate these effects. The cardiovascular system responds to melatonin and depending on receptor type and localization, melatonin can vasodilate or vasoconstrict several systemic arteries, thereby controlling whole animal nutrient partitioning via vascular resistance. Increased incidences of non-communicable diseases in populations exposed to circadian disruption have uncovered novel pathways of neurohormones, such as melatonin, influence health, and disease. Perturbations in immune function can negatively impact the growth and development of livestock which has been examined following melatonin supplementation. Specifically, melatonin can influence nutrient uptake, circulating nutrient profiles, and endocrine profiles controlling economically important livestock growth and development. This review focuses on the physiological, cellular, and molecular implications of melatonin on the health and disease of domesticated food animals.

Melatonin rescues uterine blood flow and fetal body weight in a seasonal dependent manner within a nutrient restriction bovine model. We sought to identify the effects of nutrient restriction, melatonin, and sampling time on maternal and fetal amino acids, and placental nutrient transporters. Pregnant heifers received adequate or restricted nutrition, and 20 mg of melatonin or placebo from gestational days 160–240 over two seasons. On day 240 maternal and fetal blood, amnion, and placentomes were collected. Amino acid concentrations were determined by gas chromatography-mass spectrometry. Caruncle and cotyledon tissues were assessed for nutrient transporter density by qPCR. Data were analyzed using the MIXED procedure of SAS for fixed effects. In fall, melatonin rescued effects of nutrient restriction on System N, Anion, and total maternal amino acids. Furthermore, melatonin rescued effects of nutrient restriction on Systems A, N, Br, Bo, and essential amnion amino acids. In summer, melatonin rescued effects of nutrient restriction in Systems Br and Bo maternal amino acids. Furthermore, melatonin rescued effects of nutrient restriction on caruncle SLC38A10 and SLC38A2. Melatonin rescued effects of nutrient restriction in a seasonal dependent manner. These data align with previous studies suggesting melatonin is a more effective therapeutic in summer months.

The objective of the current study was to examine the effects of maternal feed restriction and melatonin supplementation on fetal cardiomyocyte cell development parameters and predict binucleation and hypertrophy using machine learning techniques using pregnant beef heifers. Brangus heifers (n = 29) were assigned to one of four treatment groups in a 2 × 2 factorial design at day 160 of gestation: (1) 100% of nutrient requirements (adequately fed; ADQ) with no dietary melatonin (CON); (2) 100% of nutrient requirements (ADQ) with 20 mg/d of dietary melatonin (MEL); (3) 60% of nutrient requirements (nutrient-restricted; RES) with no dietary melatonin (CON); (4) 60% of nutrient requirements (RES) with 20 mg/d of dietary melatonin (MEL). On day 240 of gestation, fetuses were removed, and fetal heart weight and thickness were determined. The large blood vessel perimeter was increased in fetuses from RES compared with ADQ (p = 0.05). The total number of capillaries per tissue area exhibited a nutrition by treatment interaction (p = 0.01) where RES-MEL increased capillary number compared (p = 0.03) with ADQ-MEL. The binucleated cell number per tissue area showed a nutrition by treatment interaction (p = 0.010), where it was decreased in RES-CON vs. ADQ-CON fetuses. Hypertrophy was estimated by dividing ventricle thickness by heart weight. Based on machine learning results, for the binucleation and hypertrophy target variables, the Bagging model with 5 Decision Tree estimators and 3 Decision Tree estimators produced the best results without overfitting. In the prediction of binucleation, left heart ventricular thickness feature had the highest Gin importance weight followed by fetal body weight. In the case of hypertrophy, heart weight was the most important feature. This study provides evidence that restricted maternal nutrition leads to a reduction in the number of cardiomyocytes while melatonin treatment can mitigate some of these disturbances.