Abstract
PurposeEndometriosis (EM) is a common gynecological disease affecting 10–15% of women of reproductive age. However, molecular mechanisms and pathogenesis are still not completely understood. Furthermore, due to the absence of a reliable clinical biomarker, the only viable method for the often-delayed definitive diagnosis is laparoscopic surgery. Our objective was to analyze molecular differences of selected endometrial proteins and genes of women suffering from different stages of EM compared with healthy women to evaluate potential clinical biomarkers.MethodsWe analyzed eutopic endometrial tissue samples from women undergoing a laparoscopic surgery (n = 58). mRNA gene expression of progranulin (GRN), neurogenic locus notch homolog protein (NOTCH3), fibronectin (FN1), and PTEN-induced kinase 1 (PINK1) was analyzed using qRT-PCR. Protein expression was determined using ELISA and immunohistochemistry.ResultsSignificant differences in gene expression between the different stages of the disease were noted for GRN, NOTCH3, FN1, and PINK1 (p < 0.05). The endometrium of women with minimal EM (ASRM I) showed the highest mRNA expression. Protein levels of GRN and FN1 on the other hand were significantly decreased in the endometrium of women with EM compared with those of healthy controls. Furthermore, for GRN and FN1, we could detect a correlation of protein expression with the severity of the disease.ConclusionOur findings suggest a potential use of GRN and FN1 as clinical biomarkers to detect endometriosis. In addition, GRN, NOTCH3, FN1, and PINK1 could potentially be useful to differentiate between the underlying stages of the disease. However, a validation with a larger study population is needed.
Highlights
Endometriosis (EM) is defined as the presence of functional endometrium in any location outside the uterine cavity
Endometrial samples of 58 women were divided according to the degree of underlying EM into four categories: women without EM were used as control; women with minimal (ASRM I), mild (ASRM II), and moderate (ASRM III) EM
gene expression of progranulin (GRN) mRNA expression is considerably upregulated in women with EM compared with that in healthy controls, which may contribute to its role in inflammation and cell proliferation process
Summary
Endometriosis (EM) is defined as the presence of functional endometrium in any location outside the uterine cavity. J Assist Reprod Genet (2020) 37:2723–2732 included in this classification. None of the patients included as ASRM I and II had a deep infiltration. Various theories about the pathogenesis of EM have been submitted, none of them is proven so far and the exact causes and pathogenetic pathways of this heterogenetic disease are still not fully understood [42]. It has been suggested that within the disease, there are distinct entities and pathogenesis [24]. Clinical studies have shown different implantation rates in women with mild versus severe EM, assuming a difference in function and biochemistry of these two stages of EM [20]
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