PPARgamma in placental angiogenesis

Area of Science:

• Developmental biology
• Molecular endocrinology
• Vascular biology

Background:

• Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor regulating adipogenesis, glucose homeostasis, and inflammation.
• Previous studies on PPARγ knockout mice were limited by embryonic lethality due to placental vascular defects.

Purpose of the Study:

• To investigate the precise role of PPARγ in embryonic lethality and placental development.
• To elucidate the mechanisms by which PPARγ controls placental vasculature formation and termination.

Main Methods:

• Generation of viable PPARγ-null mice using Sox2Cre/PPARγL2/L2 genetic system for epiblast-specific deletion.
• Analysis of placental vasculature and gene expression in PPARγ-null embryos at embryonic day 9.5.
• Pharmacological treatment of pregnant wild-type mice with a PPARγ agonist (rosiglitazone) to assess late-stage placental development.

Main Results:

• PPARγ deficiency in epiblasts leads to embryonic lethality solely due to severe placental vascular defects.
• PPARγ-null placentas exhibit an imbalance of angiogenic factors, with increased proliferin (Prl2c2) and decreased proliferin-related protein (Prl7d1).
• PPARγ agonist treatment in wild-type mice disrupts placental layering, alters microvasculature, and decreases proangiogenic gene expression (Prl2c2, VEGF, Pecam1).

Conclusions:

• PPARγ is essential for normal placental vascular development and is the sole cause of embryonic lethality in PPARγ-/- embryos.
• PPARγ regulates the balance of pro- and antiangiogenic factors during placental development.
• PPARγ plays a critical role in controlling placental vascular proliferation and its timely termination in late pregnancy.