Platelet-derived growth factor BB is reduced in endometrial endothelial cells of women with abnormal uterine bleeding–endometrial disorder

Sourima Biswas Shivhare, Qinsheng Lu, Dingqian Sun, Huomei Hou, Judith N. Bulmer, Barbara A. Innes, Dharani K. Hapangama, Gendie E. Lash
In: Reproductive BioMedicine Online · 2022 · vol. 45(3) , pp. 531–543 · doi:10.1016/j.rbmo.2022.02.005 · PMID:35739007 · W4213365528
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Endometrial endothelial cells from women with abnormal uterine bleeding associated with endometrial disorders showed reduced levels of platelet-derived growth factor BB.

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Abstract

Research questionWhat is the expression pattern of platelet-derived growth factor BB (PDGF-BB), and its receptors, across the menstrual cycle in healthy control women and those with abnormal uterine bleeding-endometrial disorder (AUB-E)?DesignImmunohistochemical staining for PDGF-BB, platelet-derived growth factor receptor alpha (PDGFRα) and platelet-derived growth factor beta (PDGFRβ) was performed in control and AUB-E endometrium from the proliferative, early, mid- and late secretory phases of the menstrual cycle (n = 5 each group). Control proliferative phase endometrium was cultured in PDGF-BB (0, 10 ng/ml) and vascular maturation assessed (n = 3). Endothelial cell to vascular smooth muscle cell (VSMC) association was assessed after treatment with PDGF-BB (0, 1, 10 ng/ml). Secretion of angiogenic growth factors by endothelial cells or VSMC was determined.ResultsEndothelial cell immunoreactivity for PDGF-BB was reduced in the mid and late secretory phases in AUB-E (P = 0.008). PDGFRα was also reduced in mid secretory phase endothelial cells, proliferative and early secretory phase glandular epithelium in AUB-E (P = 0.008). PDGFRβ expression was not altered. Treatment of proliferative phase endometrium with PDGF-BB (10 ng/ml) reduced the percentage of vessels expressing contractile VSMC markers. PDGF-BB had no effect on angiogenic growth factor secretion by endothelial cells or VSMC in vitro and did not affect their association in an in-vitro endothelial cell-VSMC association assay.ConclusionsReduced endothelial cell expression of PDGF-BB in the AUB-E endometrium may contribute to the reduced vascular maturation previously observed in these women.

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