| First Author | Yessoufou A | Year | 2006 |
| Journal | Endocrinology | Volume | 147 |
| Issue | 9 | Pages | 4410-8 |
| PubMed ID | 16763063 | Mgi Jnum | J:129524 |
| Mgi Id | MGI:3769615 | Doi | 10.1210/en.2006-0067 |
| Citation | Yessoufou A, et al. (2006) Peroxisome proliferator-activated receptor alpha deficiency increases the risk of maternal abortion and neonatal mortality in murine pregnancy with or without diabetes mellitus: Modulation of T cell differentiation. Endocrinology 147(9):4410-8 |
| abstractText | We assessed the implication of peroxisome proliferator-activated receptor (PPAR) alpha deficiency in pregnancy outcome and neonatal survival and in the modulation of T cell differentiation in murine diabetic pregnancy and their offspring. Pregnant wild-type (WT) and PPAR alpha-null mice of C57BL/6J genetic background were rendered diabetic by five low doses of streptozotocin. We observed that, in the absence of diabetes, PPAR alpha deficiency resulted in an increase in abortion rate, i.e. 0% in WT mice vs. 20% in PPAR alpha-null mice [odds ratio (OR) = 14.33; P = 0.013]. Under diabetic conditions, the abortion rate was enhanced, i.e. 8.3% in WT mice vs. 50% in PPAR alpha-null mice (OR = 4.28; P = 0.011). In the pups born to diabetic dams, the offspring mortality, due to the absence of PPAR alpha, was enhanced, i.e. 27.7% in WT mice vs. 78.9% in PPAR alpha-null animals (OR = 11.48; P < 0.001). Moreover, we observed that T helper (Th) 1/Th2 balance was shifted to a pregnancy protecting Th2 phenotype in WT diabetic dams and to a noxious Th1 phenotype in PPAR alpha-null mice with diabetic pregnancy. Furthermore, offspring born to diabetic WT dams were hyperinsulinemic and hyperglycemic, and they exhibited up-regulated profile of Th2 cytokines, whereas those born to diabetic PPAR alpha-null dams were hypoinsulinemic and hyperglycemic, and they showed down-regulated profile of Th2 cytokines. However, IFN-gamma, a Th1 cytokine, was up-regulated in the offspring of both diabetic WT and PPAR alpha-null dams. Altogether, our results suggest that PPAR alpha deficiency in mice may be implicated in the increase in maternal abortion, neonatal mortality, and T cell differentiation. |
