Endocrinology; group Desvergne

Endocrinology. 2010 Sep 1. [Epub ahead of print]

PPAR{gamma} in Placental Angiogenesis.

Nadra K, Quignodon L, Sardella C, Joye E, Mucciolo A, Chrast R, Desvergne B.

Center for Integrative Genomics (K.N., L.Q., C.S., E.J., B.D.), University of Lausanne, CH-1015 Lausanne, Switzerland; and Department of Medical Genetics (K.N., R.C.) and Electron Microscopy Platform (A.M.), University of Lausanne, CH-1005 Lausanne, Switzerland.


Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor involved in diverse biological processes including adipocyte differentiation, glucose homeostasis, and inflammatory responses. Analyses of PPARgamma knockout animals have been so far preempted by the early embryonic death of PPARgamma(-/-) embryos as a consequence of the severe alteration of their placental vasculature. Using Sox2(Cre)/PPARgamma(L2/L2) mice, we obtained fully viable PPARgamma-null mice through specific and total epiblastic gene deletion, thereby demonstrating that the placental defect is the unique cause of PPARgamma(-/-) embryonic lethality. The vasculature defects observed in PPARgamma(-/-) placentas at embryonic d 9.5 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 analyze the role of PPARgamma in the later stage of placental development, when its expression peaks, we treated pregnant wild-type mice with the PPARgamma agonist rosiglitazone. This treatment resulted in a disorganization 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 PPARgamma plays a pivotal role in controlling placental vascular proliferation and contributes to its termination in late pregnancy.

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