Altered endometrial expression of endothelial nitric oxide synthase in women with unexplained recurrent miscarriage and infertility

Endothelial nitric oxide synthase (eNOS) has diverse roles in the female reproductive system including a role in blastocyst implantation. Aberrant expression of eNOS could therefore be significant in the pathogenesis of disorders of implantation. In this study, eNOS protein and mRNA levels in the endometrium of women with recurrent miscarriages, unexplained infertility and a control group were determined by compartmental quantitative immunohistochemistry and real-time reverse-transcription PCR. eNOS was found to be immunolocalized to all layers of the endometrium and vascular endothelium. eNOS protein was higher in glandular epithelium (P = 0.004) and luminal epithelium (P = 0.002), but not vascular endothelium and stroma, in women with recurrent miscarriage. Similarly, in women with unexplained infertility, eNOS was significantly higher (P < 0.03) in luminal epithelium but not in any other compartments compared with the control group. The levels of mRNA confirmed the protein data, demonstrating higher eNOS mRNA in the endometrium of women with recurrent miscarriage and unexplained infertility compared with controls. In conclusion, increased expression of eNOS in glandular and luminal epithelium of the endometrium in women with recurrent miscarriages and unexplained infertility suggests a detrimental effect of excess nitric oxide in endometrial receptivity and implantation.Endothelial nitric oxide synthase (eNOS) has diverse roles in the female reproductive system, including a role in blastocyst implantation. Aberrant expression of eNOS could therefore be significant in the pathogenesis of disorders of implantation. In this study, eNOS protein and mRNA concentrations in the endometrium of women with recurrent miscarriages, unexplained infertility and a control group were determined by compartmental quantitative immunohistochemistry and real-time reverse-transciption PCR. eNOS was found to be immunolocalized to all layers of the endometrium and vascular endothelium. eNOS protein was higher in glandular epithelium (P = 0.004) and luminal epithelium (P = 0.002) but not vascular endothelium and stroma in women with recurrent miscarriage. Similarly, in women with unexplained infertility, eNOS was significantly higher (P < 0.03) in luminal epithelium but not in any other compartments compared with the control group. The level of mRNA expression confirmed the protein data, demonstrating higher eNOS mRNA expression in the endometrium of women with recurrent miscarriage and unexplained infertility compared with controls. In conclusion, increased expression of eNOS in the glandular and luminal epithelium of the endometrium in women with recurrent miscarriages and unexplained infertility suggests a detrimental effect of excess nitric oxide in endometrial receptivity and implantation.