Effect of tocopherol supplementation on serum 8-epi-prostaglandin F2 alpha and adiponectin concentrations, and mRNA expression of PPARγ and related genes in ovine placenta and uterus

Pregnant ewes were individually given daily oral supplements of 500 mg of alpha-tocopherol (aT; N=6), 1000 mg of gamma-tocopherol (gT; N=7), or placebo (CON; N=5) from 107 to 137 d post breeding. Serum and tissue samples were collected weekly and at the end of the study, respectively. At the end of the study, in the aT, gT and CON groups, serum concentrations were 251.7 ± 12.3, 232.5 ± 6.8, and 285.8 ± 9.4 ηg/μL, respectively, for isoprostane, and were 341.7 ± 9.3, 358.7 ± 11.5, and 305.2 ± 2.8 ηg/μL for adiponectin (significantly different for aT and gT versus CON). The mRNA abundance for PPARγ in the cotyledon and caruncle were similar in aT and gT ewes. The PPARγ, ADIPQ and LEP mRNA expressions were reduced (P < 0.05) in the cotyledon and caruncle in aT versus CON ewes. However, associations of PPARγ mRNA expression with ADIPQ and LEP mRNA expressions were negatively related in cotyledons, positively related in the caruncle, and positively downregulated in the uterus in gT supplemented ewes accounting for CON. The IGF-1 mRNA expression was downregulated in the cotyledon, caruncle and uterus in aT supplemented ewes. Expression of IGF-2 mRNA was upregulated in the cotyledon and caruncle, and downregulated in the uterus in gT supplemented ewes. In conclusion, oral supplementation of tocopherol during late gestation in ewes decreased isoprostane concentrations and increased adiponectin concentrations in the serum, and significantly affected PPARγ- and ADIPQ-related genes in the utero-placental network. Perhaps the pro-angiogenic tocopherol effect in the placental vascular network was via PPARγ-mediated regulation of genes responsible for metabolism of glucose and fatty acid, as well as for angiogenesis.