Prednisolone treatment reduces endometrial spiral artery development in women with recurrent miscarriage

Angiogenesis. 2011 Dec;14(4):523-32. doi: 10.1007/s10456-011-9237-x. Epub 2011 Oct 9.

Abstract

Background: Uterine natural killer (uNK) cells and endometrial blood vessel maturation are increased in the luteal phase of the menstrual cycle in a subset of women with recurrent miscarriage (RM). uNK cell numbers are reduced after treatment with prednisolone (20 mg/day for 3 weeks).

Hypotheses: Prednisolone treatment reduces endometrial vascular maturation and angiogenic growth factor expression in women with RM with increased uNK cells.

Methods: Endometrial biopsies (n = 18 paired samples) from women with RM at LH + 7 before and during prednisolone treatment (20 mg/day for 3 weeks) were snap frozen. Total RNA and cDNA was prepared and used in a human angiogenesis RT-PCR superarray (84 genes, n = 6 pairs) with results validated using RT-PCR (n = 15 pairs). Immunohistochemistry (n = 15 pairs) was performed for Factor VIII, α-smooth muscle actin (α-SMA) and myosin heavy chain (MyHC) and the total number of vessels and the percentage of vessels completely surrounded by vascular smooth muscle cells (VSMCs) were determined.

Results: During prednisolone treatment there was no change in the total number of endometrial blood vessels but the percentage of vessels completely surrounded by VSMCs was decreased (α-SMA P < 0.0001; MyHC P < 0.0001). Endometrial EGF and STAB 1 expression was decreased during prednisolone treatment in samples from woman who went on to have a live birth.

Conclusions: The effect of prednisolone therapy for some women with RM may be due to altered endometrial angiogenic growth factor expression and reduced blood vessel maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / drug therapy*
  • Abortion, Habitual / pathology*
  • Actins / metabolism
  • Adult
  • Angiogenesis Inducing Agents / metabolism*
  • Endometrium / blood supply*
  • Endometrium / drug effects
  • Factor VIII / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Killer Cells, Natural / drug effects
  • Middle Aged
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Myosin Heavy Chains / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / physiology
  • Prednisolone / pharmacology*
  • Pregnancy
  • Pregnancy Outcome
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric
  • United Kingdom
  • Uterus / cytology
  • Uterus / immunology

Substances

  • ACTA2 protein, human
  • Actins
  • Angiogenesis Inducing Agents
  • Factor VIII
  • Prednisolone
  • Myosin Heavy Chains