Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review.

The homeobox A10 (HOXA10) gene is known to be related to endometriosis; however, due to a lack of knowledge/evidence in the pathogenesis of endometriosis, the mechanisms that link HOXA10 to endometriosis still need to be clarified. This review addresses the difference in the expression of the HOXA10 gene in endometriotic women versus non-endometriotic women across populations by country and discusses its influences on women's fertility. An organized search of electronic databases was conducted in Scopus, ScienceDirect, PubMed, and Web of Science. The keywords used were (HOXA10 OR "homeobox A10" OR PL OR HOX1 OR HOX1H OR HOX1.8) AND ("gene expression") AND (endometriosis). The initial search resulted in 623 articles, 10 of which were included in this review. All ten papers included in this study were rated fair in terms of the quality of the studies conducted. The expression of the HOXA10 gene was found to be downregulated in most studies. However, one study provided evidence of the downregulation and upregulation of HOXA10 gene expression due to the localization of endometriotic lesions. Measuring the expression of the HOXA10 gene in women is clinically essential to predicting endometriosis, endometrial receptivity, and the development of pinopodes in the endometrium during the luteal phase.

HOXA10 DNA Methylation Level in the Endometrium Women with Endometriosis: A Systematic Review.

Endometriosis is an inflammatory chronic systemic disease resulting in pelvic pain and infertility. However, despite a high prevalence of endometriosis, disease identification is still insufficient, and a high percentage of misdiagnosing was observed. Hence, a comprehensive study needs to be done to improve our understanding of the pathogenesis of endometriosis. Aberrant hypermethylation of HOXA10 has been reported to play a role in endometriosis. Thus, a comprehensive literature search was conducted to identify the DNA methylation level of HOXA10 among endometriosis patients across populations. The literature search was done using PubMed, Scopus, EBSCOhost, and Science Direct applying (HOXA10 OR "homeobox A10" OR "HOXA-10" OR HOX1) AND ("DNA methylation" OR methylation) AND (endometriosis OR endometrioma) as keywords. From 491 retrieved studies, five original articles investigating the DNA methylation level of HOXA10 from endometrium tissues among endometriosis women were included. All five included studies were classified as high-quality studies. High HOXA10 DNA methylation level was observed in the endometrium tissue of women with endometriosis in all the included studies. The secretory phase was identified as the best sampling time for HOXA10 DNA methylation study in endometriosis, and the most studied DNA methylation site is the promoter region of the HOXA10. However, more studies are needed to expose the HOXA10 mechanism in the pathogenesis of endometriosis.

Endometrial Heparin-Binding Epidermal Growth Factor Gene Expression and Hormone Level Changes in Implantation Window of Obese Women with Polycystic Ovarian Syndrome.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder amongst reproductive-age women, and 61% to 76% of women with PCOS are obese. Obese women with PCOS are usually burdened with infertility problems due to implantation failure. Thus, progesterone treatment is usually used to improve implantation rates. Although Hb-EGF expression is actively involved in endometrial receptivity and implantation, the data on heparin-binding epidermal growth factor (Hb-EGF) expression following progesterone therapy in obese women with PCOS are still lacking. OBJECTIVE: To investigate the changes in serum follicle-stimulating hormone (FSH), luteinising hormone (LH), dehydroepiandrosterone sulphate (DHEA), progesterone and oestradiol levels and Hb-EGF expression in obese women with PCOS during the implantation window following progesterone therapy. METHOD: A total of 40 participants aged 18-40 years old were recruited following the provision of written consent. The participants were divided into the obese PCOS, normal-weight PCOS, obese fertile and normal-weight fertile groups. First blood collection was done before ovulation. Then, daily oral micronised progesterone (Utrogestan 200 mg) was given to the PCOS group for 10 days. The treatment was followed by a second blood collection and endometrial tissue sampling by using a Pipelle de Cornier catheter. In the fertile group, ovulation was confirmed by using ultrasound, and a second blood sample was collected on days 7 to 9 postovulation. The serum levels of FSH, LH, DHEA, progesterone and oestradiol were measured in all participants. Wilcoxon signed-rank test was used to compare FSH, LH, DHEA, progesterone and oestradiol levels during pre- and postovulation. Mann-Whitney test was performed to compare FSH, LH, DHEA, progesterone and oestradiol levels between two groups: (1) the PCOS group and the fertile group, (2) the obese PCOS group and the non-obese PCOS group and (3) the obese group and the non-obese fertile group. RESULT: Serum FSH levels were lower in obese women in their follicular phase than in women with normal weight regardless of their PCOS status, whereas serum LH/FSH ratios and DHEA levels were higher in women with PCOS than in women without PCOS. However, endometrial Hb-EGF expression was lower in the obese PCOS group than in the normal-weight PCOS group. CONCLUSIONS: Different patterns of hormonal levels and Hb-EGF expression levels were seen between the studied groups. However, further in vitro and in vivo studies are needed to investigate the mechanism underlying the changes in FSH, LH/FSH ratio, DHEA and Hb-EGF expression in PCOS after progesterone treatment.

A Systematic Review and Integrated Bioinformatic Analysis of Candidate Genes and Pathways in the Endometrium of Patients With Polycystic Ovary Syndrome During the Implantation Window.

Polycystic ovary syndrome (PCOS) is a common disorder with wide-ranging clinical heterogeneity that causes infertility. However, the comprehensive molecular mechanisms of PCOS in causing infertility is remaining unclear. Hence, a comprehensive literature search was conducted using PubMed, Scopus, EBSCOhost, and Science Direct. Medical Subject Heading (MeSH) terms like PCOS, gene expression, implantation window and endometrium were used as the keywords. From 138 studies retrieved, original articles with RNA profiling on human endometrial tissues in PCOS women during the implantation window were included. Study design, sample size, sample type, method, and differentially expressed genes (DEGs) were identified from all publications. The DEGs were analyzed using the software packages DAVID, STRING, and Cytoscape. Three studies that met inclusion criteria were included, and 368 DEGs were identified. Twelve significant clusters from the protein-protein interaction network (PPI) complex were found, and cluster 1 showed very high intermolecular interactions. Five candidate genes (AURKA, CDC25C, KIF23, KIF2C, and NDC80) were identified from the systematic review and integrated bioinformatics analysis. It is concluded that cell cycle is the fundamental biological processes that were dysregulated in the endometrium of PCOS women, affecting decidualization progression in the endometrium during the implantation window.