METHODS: Eutopic endometrium and serum from patients with endometriosis (n = 8 for tissue and n = 4 for serum) are, respectively, compared to endometrium and serum from females without endometriosis (n = 8 for tissue and n = 4 for serum) using a shotgun quantitative proteomics method. All study participants are at the proliferative phase of their menstrual cycle.
RESULTS: At the tissue and serum level, 1214 and 404 proteins are differentially expressed (DEPs) in eutopic endometrium and serum, respectively, of women with endometriosis versus controls. Gene ontology analysis shows that terms related to immune response/inflammation, cell adhesion/migration, and blood coagulation are significantly enriched in the DEPs of eutopic endometrium, as well as serum. Twenty-one DEPs have the same trend of differential expression in both matrices and can be further examined as potential disease- and tissue-specific serological markers of endometriosis.
CONCLUSIONS: The present integrated proteomic profiling of eutopic endometrium and serum from women with endometriosis identify promising serological markers that can be further validated in larger cohorts for the minimally invasive diagnosis of endometriosis.
AIM: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC.
DESIGN AND METHODS: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study.
RESULTS: We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P
METHODS: Female Sprague-Dawley rats were ovariectomized and received 3-days estradiol-17β benzoate (E2) plus genistein (25, 50, or 100 mg kg(-1) day(-1) ) or 3-days E2 followed by 3-days E2 plus progesterone with genistein (25, 50, or 100 mg kg(-1) day(-1) ). A day after last treatment, uterine fluid secretion rate was determined by in vivo uterine perfusion with rats under anesthesia. Animals were sacrificed and uteri were harvested and subjected for histological analyses. Luminal/outer uterine circumference was determined and distribution of AQP-1, 2, 5, and 7 in endometrium was visualized by immunofluorescence. Expression of AQP-1, 2, 5, and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR respectively.
RESULTS: Combined treatment of E2 with high dose genistein (50 and 100 mg kg(-1) day(-1) ) resulted in significant decrease in uterine fluid volume, secretion rate and expression of AQP-1, 2, 5, and 7 proteins and mRNAs in uterus (p
MATERIAL AND METHODS: A cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed.
RESULTS: The body mass indices of women with polycystic ovary syndrome (29.28 ± 2.91 kg/m(2) ) and controls (28.58 ± 2.62 kg/m(2) ) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 ± 5.70 kg/m(2) ). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p endometrium of women with polycystic ovary syndrome and women with endometrial cancer compared with controls and positively correlates with serum triglyceride in both polycystic ovary syndrome and endometrial cancer.