Immunohistochemical Localization of Endothelial Nitric Oxide Synthase in Endometrial Tissues of Women With Uterine Myomas

Abstract

Objectives: Nitric oxide (NO) is a free radical that plays important roles in variety of physiological aspects of the female reproductive system. Pathophysiological findings revealed a potential role of the endothelial isoform of nitric oxide synthase (eNOS) enzyme in female reproductive disorders specifically in the endometrium. This study investigates the expression of eNOS in the endometrial tissue to study the potential role of this enzyme and its NO production in infertility of women with uterine myomas. Materials and Methods: A total of 20 endometrial tissues were obtained, 10 infertile women with uterine fibroids and 10from normal and fertile women, 7 to 9 days after LH surge. Following fixation with paraformaldhyde, frozen sections of samples were prepared for semi-quantitative immunohistochemical evaluation using monoclonal anti-human eNOS antibody. Hematoxylin and eosin staining was used for histological dating of the samples Results: Localization of eNOS was seen in glandular and luminal epithelium, vascular endothelium and stroma in both fertile women and infertile women with uterine fibroids. Despite the differences in immunoreactivity of luminal epithelium, vascular endothelium and stroma in both groups, higher levels of eNOS in glandular epithelium was statistically significant in women with uterine fibroids compared to the control group. Conclusions: The findings suggest that over-expression of eNOS in glandular epithelium may affect the preparation stage of endometrium for fertility in women with uterine myomas.

Endometrial Angiogenesis of Abnormal Uterine Bleeding and Infertility in Patients with Uterine Fibroids—A Systematic Review

“…Our review shows increased levels of eNOS in the endometrium of patients with fibroids and infertility. As eNOS is important in continuing pregnancy and uterine quiescence during implantation, this supports the hypotheses that fibroids can impair implantation or increase the risk of miscarriage [ 49 ]. Remarkably, in patients with fibroids and AUB, eNOS was also significantly increased [ 35 , 80 ], supporting the idea that eNOS expression is increased in the endometrium due to the presence of fibroids.…”

“…eNOS overexpression can induce cellular apoptosis and/or result in nitrosylation of key signaling proteins. Thus, increased eNOS expression may impair endometrial and myometrial function [ 49 , 64 ]. The overexpression of endometrial eNOS is described for endometriosis, adenomyosis, recurrent miscarriages, and unexplained infertility [ 65 , 66 ].…”

“…The overexpression of endometrial eNOS is described for endometriosis, adenomyosis, recurrent miscarriages, and unexplained infertility [ 65 , 66 ]. Since fibroids are an estrogen-, and progesterone-dependent pathology and endometrial eNOS is also regulated by these hormones, eNOS overexpression might be an important factor for patients with fibroids and infertility [ 49 ].…”

“…It is important to note that all studies used different inclusion criteria for the study and control group, as seen in basic characteristics which are displayed in Table 3 . The study of Novin et al 2018 found an increased expression of eNOS in infertile patients with fibroids compared to fertile controls without fibroids [ 49 ]. The study of Kozachenko et al 2020 compared the endometrium of infertile patients with fibroids to infertile patients without fibroids, although this was classified as poor quality in our RoB analysis.…”

Infertility in patients with uterine fibroids: a debate about the hypothetical mechanisms

“…, 2012 ). In infertile women with fibroids higher levels of eNOS were found compared to normal controls; while eNOS stimulates myometrial quiescence during pregnancy, overexpression can induce cellular apoptosis and/or impair endometrial and myometrial functions ( Novin etal. , 2018 ).…”