PPARγ Expression Is Diminished in Macrophages of Recurrent Miscarriage Placentas

Int J Mol Sci. 2018 Jun 26;19(7):1872. doi: 10.3390/ijms19071872.

Abstract

PPARγ belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPARγ is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPARγ under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion and 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPARγ. Expression changes were evaluated by immunohistochemistry and real time PCR (RT-PCR) in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using cluster of differentiation 68 (CD68) as marker for macrophages and further characterized regarding their M1/M2 polarization status. The intermediate villous trophoblast revealed a significantly lower PPARγ expression in spontaneous and recurrent abortion. Maternal macrophages express PPARγ. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPARγ only in very few cases. PPARγ is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPARγ in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus.

Keywords: PPARγ; decidual macrophages; first trimester placenta; miscarriage.

MeSH terms

  • Abortion, Habitual / genetics*
  • Abortion, Habitual / pathology*
  • Adolescent
  • Adult
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • CX3C Chemokine Receptor 1 / metabolism
  • Chemokine CCL1 / metabolism
  • Decidua / metabolism
  • Decidua / pathology
  • Demography
  • Female
  • Humans
  • Macrophages / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • Placenta / metabolism*
  • Placenta / pathology*
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Toll-Like Receptor 2 / metabolism
  • Trophoblasts / metabolism
  • Trophoblasts / pathology
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Chemokine CCL1
  • PPAR gamma
  • RNA, Messenger
  • Toll-Like Receptor 2
  • Nitric Oxide Synthase Type II