The involvement of the progesterone receptor in PIBF and Gal-1 expression in the mouse endometrium

Am J Reprod Immunol. 2019 May;81(5):e13104. doi: 10.1111/aji.13104. Epub 2019 Mar 22.

Abstract

Problem: The progesterone-regulated genes, PIBF and Gal-1, are key players in the feto-maternal immunological interaction. This study aims to investigate the expression of PIBF and Gal-1 in WT and progesterone receptor KO models as well as subsequent effects of PIBF on decidualization of stromal cells.

Method of the study: PRAKO, PRBKO and PRKO BALB/c mice were used for assessing the role of PR isoforms in PIBF induction. PIBF- and Gal-1 mRNA expression in the uterus was tested by real-time PCR. The effect of PIBF on decidualization of endometrial stromal cells was verified by anti-desmin immunofluorescence. Immunohistochemistry was used for testing PIBF expression in the uterus. Gal-1, ERα and PR positive decidual NK cells were detected by immunofluorescence.

Results: PIBF mRNA was significantly increased in progesterone-treated WT mice, but not in PRKO and PRAKO mice. PIBF protein expression was reduced in the endometria of PRKO and PRAKO, but not in PRBKO mice. During a 6-day culture, PIBF induced decidual transformation of endometrial stromal cells. PIBF expression in the mouse uterus was highest during the implantation window, while Gal-1 mRNA expression continuously increased between day 2.5 and day 11.5 of gestation. Decidual NK cells express Gal-1 and ERα, but not PR at day 7.5 murine pregnancy.

Conclusion: PIBF produced via engagement of PRA, is highly expressed in the endometrium during the implantation window, and plays a role in decidualization. The concerted action of PIBF and Gal-1 might contribute to the low cytotoxic activity of decidual NK cells.

Keywords: Gal-1; PIBF; decidual NK cells; decidualization; progesterone receptor isoforms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / metabolism*
  • Cells, Cultured
  • Decidua / physiology*
  • Embryo Implantation
  • Endometrium / cytology
  • Endometrium / metabolism*
  • Female
  • Gene Expression Regulation
  • Immune Tolerance
  • Maternal-Fetal Exchange / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Models, Animal
  • Pregnancy
  • Pregnancy Proteins / genetics
  • Pregnancy Proteins / metabolism*
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism*
  • Stromal Cells / physiology*
  • Tyrosine / analogs & derivatives*
  • Tyrosine / genetics
  • Tyrosine / metabolism

Substances

  • Benzamides
  • Pibf1 protein, mouse
  • Pregnancy Proteins
  • Receptors, Progesterone
  • Tyrosine
  • 1-nitrohydroxyphenyl-N-benzoylalanine