Tags

Type your tag names separated by a space and hit enter

Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis.
Reprod Biol Endocrinol. 2012 Sep 24; 10:84.RB

Abstract

BACKGROUND

In order to obtain a lead of the pathophysiology of endometriosis, genome-wide expressional analyses of eutopic and ectopic endometrium have earlier been reported, however, the effects of stages of severity and phases of menstrual cycle on expressional profiles have not been examined. The effect of genetic heterogeneity and fertility history on transcriptional activity was also not considered. In the present study, a genome-wide expression analysis of autologous, paired eutopic and ectopic endometrial samples obtained from fertile women (n=18) suffering from moderate (stage 3; n=8) or severe (stage 4; n=10) ovarian endometriosis during proliferative (n=13) and secretory (n=5) phases of menstrual cycle was performed.

METHODS

Individual pure RNA samples were subjected to Agilent's Whole Human Genome 44K microarray experiments. Microarray data were validated (P<0.01) by estimating transcript copy numbers by performing real time RT-PCR of seven (7) arbitrarily selected genes in all samples. The data obtained were subjected to differential expression (DE) and differential co-expression (DC) analyses followed by networks and enrichment analysis, and gene set enrichment analysis (GSEA). The reproducibility of prediction based on GSEA implementation of DC results was assessed by examining the relative expressions of twenty eight (28) selected genes in RNA samples obtained from fresh pool of eutopic and ectopic samples from confirmed ovarian endometriosis patients with stages 3 and 4 (n=4/each) during proliferative and secretory (n=4/each) phases.

RESULTS

Higher clustering effect of pairing (cluster distance, cd=0.1) in samples from same individuals on expressional arrays among eutopic and ectopic samples was observed as compared to that of clinical stages of severity (cd=0.5) and phases of menstrual cycle (cd=0.6). Post hoc analysis revealed anomaly in the expressional profiles of several genes associated with immunological, neuracrine and endocrine functions and gynecological cancers however with no overt oncogenic potential in endometriotic tissue. Dys-regulation of three (CLOCK, ESR1, and MYC) major transcription factors appeared to be significant causative factors in the pathogenesis of ovarian endometriosis. A novel cohort of twenty-eight (28) genes representing potential marker for ovarian endometriosis in fertile women was discovered.

CONCLUSIONS

Dysfunctional expression of immuno-neuro-endocrine behaviour in endometrium appeared critical to endometriosis. Although no overt oncogenic potential was evident, several genes associated with gynecological cancers were observed to be high in the expressional profiles in endometriotic tissue.

Authors+Show Affiliations

Department of Physiology, All India Institute of Medical Sciences, New Delhi, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23006437

Citation

Khan, Meraj A., et al. "Genome-wide Expressions in Autologous Eutopic and Ectopic Endometrium of Fertile Women With Endometriosis." Reproductive Biology and Endocrinology : RB&E, vol. 10, 2012, p. 84.
Khan MA, Sengupta J, Mittal S, et al. Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis. Reprod Biol Endocrinol. 2012;10:84.
Khan, M. A., Sengupta, J., Mittal, S., & Ghosh, D. (2012). Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis. Reproductive Biology and Endocrinology : RB&E, 10, 84. https://doi.org/10.1186/1477-7827-10-84
Khan MA, et al. Genome-wide Expressions in Autologous Eutopic and Ectopic Endometrium of Fertile Women With Endometriosis. Reprod Biol Endocrinol. 2012 Sep 24;10:84. PubMed PMID: 23006437.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis. AU - Khan,Meraj A, AU - Sengupta,Jayasree, AU - Mittal,Suneeta, AU - Ghosh,Debabrata, Y1 - 2012/09/24/ PY - 2012/07/06/received PY - 2012/08/28/accepted PY - 2012/9/26/entrez PY - 2012/9/26/pubmed PY - 2013/6/7/medline SP - 84 EP - 84 JF - Reproductive biology and endocrinology : RB&E JO - Reprod. Biol. Endocrinol. VL - 10 N2 - BACKGROUND: In order to obtain a lead of the pathophysiology of endometriosis, genome-wide expressional analyses of eutopic and ectopic endometrium have earlier been reported, however, the effects of stages of severity and phases of menstrual cycle on expressional profiles have not been examined. The effect of genetic heterogeneity and fertility history on transcriptional activity was also not considered. In the present study, a genome-wide expression analysis of autologous, paired eutopic and ectopic endometrial samples obtained from fertile women (n=18) suffering from moderate (stage 3; n=8) or severe (stage 4; n=10) ovarian endometriosis during proliferative (n=13) and secretory (n=5) phases of menstrual cycle was performed. METHODS: Individual pure RNA samples were subjected to Agilent's Whole Human Genome 44K microarray experiments. Microarray data were validated (P<0.01) by estimating transcript copy numbers by performing real time RT-PCR of seven (7) arbitrarily selected genes in all samples. The data obtained were subjected to differential expression (DE) and differential co-expression (DC) analyses followed by networks and enrichment analysis, and gene set enrichment analysis (GSEA). The reproducibility of prediction based on GSEA implementation of DC results was assessed by examining the relative expressions of twenty eight (28) selected genes in RNA samples obtained from fresh pool of eutopic and ectopic samples from confirmed ovarian endometriosis patients with stages 3 and 4 (n=4/each) during proliferative and secretory (n=4/each) phases. RESULTS: Higher clustering effect of pairing (cluster distance, cd=0.1) in samples from same individuals on expressional arrays among eutopic and ectopic samples was observed as compared to that of clinical stages of severity (cd=0.5) and phases of menstrual cycle (cd=0.6). Post hoc analysis revealed anomaly in the expressional profiles of several genes associated with immunological, neuracrine and endocrine functions and gynecological cancers however with no overt oncogenic potential in endometriotic tissue. Dys-regulation of three (CLOCK, ESR1, and MYC) major transcription factors appeared to be significant causative factors in the pathogenesis of ovarian endometriosis. A novel cohort of twenty-eight (28) genes representing potential marker for ovarian endometriosis in fertile women was discovered. CONCLUSIONS: Dysfunctional expression of immuno-neuro-endocrine behaviour in endometrium appeared critical to endometriosis. Although no overt oncogenic potential was evident, several genes associated with gynecological cancers were observed to be high in the expressional profiles in endometriotic tissue. SN - 1477-7827 UR - https://www.unboundmedicine.com/medline/citation/23006437/Genome_wide_expressions_in_autologous_eutopic_and_ectopic_endometrium_of_fertile_women_with_endometriosis_ L2 - https://rbej.biomedcentral.com/articles/10.1186/1477-7827-10-84 DB - PRIME DP - Unbound Medicine ER -