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Prednisolone treatment reduces endometrial spiral artery development in women with recurrent miscarriage
Gendie E Lash1, Judith N Bulmer, Barbara A Innes
1Reproductive and Vascular Biology Group, Institute of Cellular Medicine, Newcastle University, 3rd Floor, William Leech Building, Newcastle upon Tyne, NE2 4HH, UK. g.e.lash@ncl.ac.uk
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.
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