Tesi di dottorato di ricerca
peroxisome proliferator-activated receptor gamma (PPAR-gamma) in placental angiogenesis
Settore scientifico disciplinare
Corso di studi
SCIENZE ENDOCRINE E METABOLICHE
tutor Prof. Martino, Enio
Data inizio appello
Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor involved in diverse biological processes including adipocyte differentiation, glucose homeostasis and inflammatory responses. Analyses of PPARγ knock-out animals have been so far pre-empted by the early embryonic death of PPARγ–/– embryos as a consequence of the severe alteration of their placental vasculature. Using Sox2CRE/PPARγL2/L2 mice we obtained fully viable PPARγ null mice through specific and total epiblastic gene deletion, thereby demonstrating that the placental defect is the unique cause of PPARγ–/– embryonic lethality. The vasculature defects observed in PPARγ–/– placentas at E9.5 correlated with an unsettled balance of pro- and antiangiogenic factors as demonstrated by increased levels of proliferin (Prl2c2, PLF) and decreased levels of proliferin-related protein (Prl7d1, PRP) respectively. To analyse the role of PPARγ in the later stage of placental development, when its expression peaks, we treated pregnant wild-type mice with the PPARγ agonist rosiglitazone. This treatment resulted in a disorganisation of the placental layers and an altered placental microvasculature, accompanied by the decreased expression of proangiogenic genes such as Prl2c2, vascular endothelial growth factor and Pecam1. Together our data demonstrate that PPARγ plays a pivotal role in controlling placental vascular proliferation and contributes to its termination in late pregnancy.