Characterizing Fetal Liver and Placental Steroid and Eicosanoid Metabolizing Enzymes from Dams Supplemented with Melatonin

Melatonin is a strong antioxidant that contributes to circadian rhythm in several mammalian species. Melatonin has been shown to influence uteroplacental hemodynamics in both sheep and cattle. The objective was to examine fetal liver and placental steroid and eicosanoid enzyme activity during maternal melatonin supplementation. Commercial beef heifers (n = 12) were bred via AI and delegated to receive two, 24 mg sub-dermal melatonin implants (MEL; n = 6) or act as part of a non-implant control group (CON; n = 6). All treatments were applied at d 180, 210, and 240 of gestation, and heifers underwent Caesarian removal of the fetus at 243 ± 2 d of gestation. Placental samples were collected and separated into maternal (caruncle; CAR) and fetal (cotyledon; COT) portions. Additionally, the fetal liver was harvested. Cytochrome P450 1A (CYP1A), 2C (CYP2C), 3A (CYP3A), and uridine 5’-diphospho-glucuronosyltransferase (UGT) activities were determined via luminogenic substrates. Activities were expressed per mg of protein, and data were analyzed, using the Wilcoxon rank sum test, within tissue using the MIXED procedure of SAS (SAS Inst. Inc., Cary, NC) with treatment, fetal sex, and the interaction thereof in the model. Statistical significance was declared at P ≤ 0.05. Activity of CYP1A in CAR was decreased (P = 0.02) in male vs. female fetuses from CON dams. Activity of CYP1A was not different (P ≥ 0.25) in COT tissues; however, activity of CYP1A in fetal liver was increased (P = 0.01) in male vs. female fetuses. Activity of CYP2C was only observed in CAR and was not different between treatments (P ≥ 0.59). Activity of CYP3A was only observed in fetal liver and was not different between treatments (P ≥ 0.41). Activity of UGT in COT was decreased (P = 0.03) in male fetuses from MEL dams vs. female fetuses from MEL dams and male fetuses from CON dams. Activity of UGT was not different (P ≥ 0.34) between treatments in CAR; however, activity of UGT was increased (P = 0.002) in fetal liver from MEL dams compared to fetal liver from CON dams. In conclusion, melatonin supplementation did alter hormone metabolizing enzymes in fetal liver and placental tissues of gestating cattle. Moreover, the difference in activity of steroid and eicosanoid metabolizing enzymes in male and female fetuses may indicate a physiological adaptation to decrease excessive exposure.