Dysregulated uterine natural killer cells and vascular remodeling in women with recurrent pregnancy losses

ProblemAngiogenesis and vascular remodeling in secretory endometrium represent one of the crucial steps in pregnancy establishment, for which uterine NK (uNK) cells have an important role. Impairment of these steps may proceed to implantation and instigate initial pathology of recurrent pregnancy losses (RPL). In this study, we aim to investigate vascular development and density of uNK cells in secretory endometrium of women with RPL. Methods of studyMid-secretory phase endometrial tissues from women with RPL (n=15) and fertile controls (n=7) were investigated. CD56(+) and CD16(+) uNK cells, CD31(+) vascular endothelial cells and smooth muscle myosin (SMM)(+). Vascular smooth muscle cells (VSMC) expressing SMM were investigated using immunohistochemistry and western blot. High-throughput quantitative real-time polymerase chain reaction (qRT-PCR) was used as well. ResultsCD56(+) uNK number was significantly higher in women with RPL compared to controls (P<0.0001). uNK cell density by immunohistochemistry was positively correlated with CD56 mRNA expression by qRT-PCR (r(2)=0.43, P=0.0137). The number of blood vessels represented by the expression of either CD31 or SMM was higher in women with RPL as compared to controls (P<0.05 and P<0.0001, respectively), and correlated with the number of uNK cell (r(2)=0.18, P<0.04, and r(2)=0.65, P<0.0001, respectively). The wall thickness of spiral arteries was significantly higher in women with RPL as compared with that of controls (P=0.0027). ConclusionIncreased uNK cells in mid-secretory endometrium are associated with increased vascularization and defective vascular transformation of spiral arteries in women with RPL.