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

Abstract

Background 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 Materials and Methods eNOS protein and mRNA levels in the endometrium of women with recurrent miscarriages, unexplained infertility, and a control group was determined by compartmental quantitative immunohistochemistry and real time RT-PCR Results eNOS was immunolocalized to all layers of the endometrium and the vascular endothelium. eNOS protein expression was higher in glandular epithelium (P=0.004) and luminal epithelium (P=0.002) but not vascular endothelium and stroma (P=0.14) in women with recurrent miscarriage. Similarly, in women with unexplained infertility eNOS expression was significantly higher (P<0.03) in luminal epithelium but not in any other compartments compared with the control group. The levels of mRNA expression as determined by real time RT-PCR confirmed the protein data demonstrating higher eNOS mRNA expression In the endometrium of women with recurrent miscarriage and unexplained infertility compared with controls 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

Polymorphisms in the endothelial nitric oxide synthase gene associated with recurrent miscarriage

“…Recently, eNOS has been reported to be overexpressed in the glandular and luminal epithelium of the endometrium in women with RM and unexplained infertility, suggesting a detrimental effect of excess NO on endometrial receptivity and implantation (Najafi et al, 2012). In humans, abnormal levels of NO as well as polymorphic variants of eNOS have been shown to play important roles in pregnancy-related vascular disease (Hefler et al, 2002;Hillermann et al, 2005;Huber et al, 2005;Suryanarayana et al, 2006;Yoshimura et al, 2001).…”

Endothelial Nitric Oxide Synthase Gene Polymorphisms (Promoter -786T/C, Exon 894 G/T and Intron G10T) in Unexplained Female Infertility

“…Abnormal eNOS expression could have a role in the pathogenesis of implantation disorders. eNOS was reported to be significantly higher in luminal epithelium of women with unexplained infertility compared to the control group [23]. Also higher eNOS mRNA levels were found in the endometrium of women with recurrent miscarriage and unexplained infertility compared to the control group [23].…”

“…eNOS was reported to be significantly higher in luminal epithelium of women with unexplained infertility compared to the control group [23]. Also higher eNOS mRNA levels were found in the endometrium of women with recurrent miscarriage and unexplained infertility compared to the control group [23]. Although we found that eNOS exon 894 G/T polymorphism was significantly higher in the infertile group compared to the control group, the difference between the two groups was not significant for other eNOS gene polymorphisms (T-786C and G10T).…”

Oxidative Stress in Unexplained Female Infertility

“…eNOS mRNA in the endometrium of the women with unexplained infertility was significantly higher compared with controls [155]. Its increased expression suggests the detrimental effect of NO in endometrial receptivity and implantation [155]. Excess NO could impair implantation through several mechanisms.…”

“…It disturbs the endometrium and contributes to poor oocyte quality [152]. eNOS mRNA in the endometrium of the women with unexplained infertility was significantly higher compared with controls [155]. Its increased expression suggests the detrimental effect of NO in endometrial receptivity and implantation [155].…”