Activin A, Activin Receptor Type II, Nodal, and Cripto mRNA Are Expressed by Eutopic and Ectopic Endometrium in Women With Ovarian Endometriosis

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Activin A mRNA expression was elevated in eutopic endometrium of endometriosis patients, while cripto mRNA was lower in both eutopic and ectopic endometrium compared to controls.

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This study measured mRNA levels of activin A, activin receptor type II (ActRII), nodal, and cripto in eutopic endometrium from 15 women with ovarian endometrioma and 15 healthy controls, and additionally in ectopic endometrium from the patients, using real-time PCR with attention to menstrual cycle phase. Activin A mRNA was significantly higher in patients’ eutopic endometrium than in controls, with the increase reported in both proliferative and secretory phases, whereas ActRII and nodal mRNA were similar between patients and controls; cripto mRNA was markedly lower in both proliferative-phase eutopic endometrium and ectopic endometrium from patients compared with healthy controls’ eutopic endometrium. A key caveat is the small sample size (n=15 per group for controls and patients) and reliance on mRNA expression rather than protein signaling activity. Relevance to endometriosis: the authors directly compare gene expression in eutopic and ectopic endometrium from women with ovarian endometrioma and conclude that altered activin system expression may be involved in endometrial changes in endometriosis. This paper is centrally about endometriosis — it characterizes activin pathway and cripto/nodal-related gene expression differences between eutopic and ectopic endometrium in ovarian endometrioma patients.

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Abstract

Activin A is a dimeric protein that regulates endometrial functions by signaling at its receptors, namely type I (ActRI) and type II (ActRII). Nodal is an activin competitor that requires the coreceptor cripto to assemble its signaling pathway through ActRI and ActRII. In the current study, we evaluated the expression of activin A, ActRII, nodal, and cripto in eutopic and ectopic endometrium collected from women with ovarian endometrioma (n = 15) and in eutopic endometrium of healthy participants (n = 15). Eutopic endometrial samples were evaluated according to the stage of menstrual cycle. Total RNA was extracted from tissue homogenates and analyzed by real-time polymerase chain reaction (PCR). Activin A messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis was significantly higher than in controls (P < .001) with a 10.2-fold and 7.3-fold increase in the proliferative and secretory phases, respectively. ActRII and nodal mRNA expression were found to be similar in patients with and without endometriosis, while cripto mRNA was markedly lower in eutopic (fold change = 0.03 at proliferative phase, P < .001) and ectopic endometrium (fold change = 0.14, P < .001) of women with endometriosis compared with eutopic endometrium from healthy controls. In conclusion, the altered endometrial expression of activin A and cripto during the menstrual cycle and the differences observed in the endometriotic tissue support the involvement of the activin system in endometrial changes of women with endometriosis.
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Abstract

Activin A is a dimeric protein that regulates endometrial functions by signaling at its receptors, namely type I (ActRI) and type II (ActRII). Nodal is an activin competitor that requires the coreceptor cripto to assemble its signaling pathway through ActRI and ActRII. In the current study, we evaluated the expression of activin A, ActRII, nodal, and cripto in eutopic and ectopic endometrium collected from women with ovarian endometrioma (n = 15) and in eutopic endometrium of healthy participants (n = 15). Eutopic endometrial samples were evaluated according to the stage of menstrual cycle. Total RNA was extracted from tissue homogenates and analyzed by real-time polymerase chain reaction (PCR). Activin A messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis was significantly higher than in controls (P < .001) with a 10.2-fold and 7.3-fold increase in the proliferative and secretory phases, respectively. ActRII and nodal mRNA expression were found to be similar in patients with and without endometriosis, while cripto mRNA was markedly lower in eutopic fold change = 0.03 at proliferative phase, P < .001) and ectopic endometrium fold change = 0.14, P < .001) of women with endometriosis compared with eutopic endometrium from healthy controls. In conclusion, the altered endometrial expression of activin A and cripto during the menstrual cycle and the differences observed in the endometriotic tissue support the involvement of the activin system in endometrial changes of women with endometriosis. Similar content being viewed by others

References

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Sci. 16, 727–733 (2009). https://doi.org/10.1177/1933719109334967 Published: Issue date: DOI: https://doi.org/10.1177/1933719109334967

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endometriosis

MeSH descriptors

Activin Receptors, Type II Activins Choristoma Endometriosis Endometrium Epidermal Growth Factor Membrane Glycoproteins Neoplasm Proteins Nodal Protein Ovarian Diseases Activin Receptors, Type II Activins Adult Case-Control Studies Endometriosis Epidermal Growth Factor Female GPI-Linked Proteins Humans Intercellular Signaling Peptides and Proteins

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