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

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Uterine myomas or fibroids are known as the most prevalent benign solid tumors of the female reproductive system. They are commonly found in the myometrial layer of the uterus; however… Click to show full abstract

Uterine myomas or fibroids are known as the most prevalent benign solid tumors of the female reproductive system. They are commonly found in the myometrial layer of the uterus; however their presence in other different locations both inside and outside the uterus has been reported. Although myomas are very prevalent and are diagnosed in 25%–50% of females, the exact pathogenesis has not been determined; however, it has been reported that these tumors are derived from myoma cells by the intervention of specific hormones (1). Uterine myomas can diversely affect normal pathophysiology of reproductive system and cause pain, infertility, pregnancy loss, menorrhagia and many other complications through different mechanisms. Moreover, they could reduce the efficacy of assisted reproductive technologies and the implantation rate (2). Studies have proven that intramural and submucosal fibroids could lower the rate of fertility (3). Since 1980, surgical myomectomy is routinely used as a common treatment procedure for patients with uterine myomas; this technique has been approved for its outstanding advantages in medical, social and economic terms by decreasing morbidity (4). However, in many cases, due to their asymptomatic nature, uterine myomas do not necessarily need to be removed. Nitric oxide (NO) is a free radical that plays diverse physiological roles in human systems. Nitric oxide synthase (NOS) is the name given to a group of enzymes which produce NO from L-arginine amino acid. In the human endometrial tissue, all three isoforms of NOS (iNOS, eNOS and nNOS) are expressed; However the endothelial isoform (eNOS) is the predominant one(5). To date, we do know eNOS acts as a regulator of uterine quiescence during the gestational period and studies have demonstrated its role in signal transduction pathways (6) as well as relaxation of myometrial smooth muscles (7,8). Even though the release of eNOS is a critical factor to maintain pregnancy, over-expression of this enzyme has been shown to induce cellular apoptosis (9) and/or impair endometrial and myometrial function by nitrosylation of key endometrial proteins (10,11) as well as subsequent effects on myometrial relaxation. The same conditions also have been reported in the state of endometriosis (12-14), adenomyosis (15), unexplained infertility, and 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.

Keywords: oxide synthase; nitric oxide; endometrial tissues; uterine myomas; women uterine

Journal Title: International Journal of Women's Health
Year Published: 2018

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