Serum miR-451a Levels Are Significantly Elevated in Women With Endometriosis and Recapitulated in Baboons (Papio anubis) With Experimentally-Induced Disease

Nothnick WB, Warren B Nothnick, Falcone T, Tommaso Falcone, Niraj Joshi, Fazleabas AT, Asgerally T Fazleabas, Graham A, Amanda Graham
Reproductive sciences (Thousand Oaks, Calif.) · 2016 · vol. 24(8) , pp. 1195–1202 · doi:10.1177/1933719116681519 · PMID:27920341 · PMC6343454 · W2559991815
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Serum miR-451a levels are significantly elevated in women with endometriosis, positively correlate with lesion content, and are recapitulated in baboons with experimentally-induced disease.

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This study measured circulating microRNA-451a (miR-451a) in 81 women undergoing laparoscopy, comparing serum miR-451a levels in patients with confirmed endometriosis versus controls without visible signs or symptoms, and assessed whether serum levels correlated with miR-451a content in matched endometriotic lesions and eutopic endometrium using qRT-PCR. In humans, serum miR-451a was significantly higher in women with endometriosis, and serum levels positively correlated with lesion miR-451a content, yielding an AUC of 0.8599 for distinguishing cases from controls; the authors note that miR-451a did not differ by menstrual cycle stage, endometriosis stage, or medications, which they collapsed for analysis. The study also induced endometriosis in baboons and found serum miR-451a peaked at 6 months postinduction. This paper is centrally about endometriosis — it evaluates whether serum miR-451a distinguishes women with endometriosis and correlates with lesion expression, with validation in an experimentally induced baboon model.

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Abstract

We have previously demonstrated that human microRNA-451a (miR-451a) endometriotic lesion expression is significantly higher compared to that of the corresponding eutopic endometrium. The objective of the current study was to examine the relationship between lesion and serum content of miR-451a and to determine the utility of serum miR-451a in distinguishing between women with and without visible signs of endometriosis. Eighty-one participants were enrolled in this study, 41 with confirmed endometriosis and 40 without visible signs of endometriosis at laparoscopy (n = 20) or symptoms of endometriosis (pain, infertility n = 20). Experimental endometriosis was also induced in 8 baboons. Blood, endometriotic lesions, and eutopic endometrial samples were collected from women undergoing laparoscopy for surgical removal of endometriosis. Blood was also collected from control participants with no signs and symptoms associated with the disease as well as from baboons prior to, and then 1, 3, 6, 9, and 15 months postinduction of endometriosis. MicroRNA-451a was assessed by quantitative real-time polymerase chain reaction in all samples. In humans, serum miR-451a levels positively correlated with endometriotic lesion miR-451a content, and sera levels were significantly higher in these participants compared to controls. The area under the curve (AUC) for miR-451a was 0.8599. In baboons, serum miR-451a reached statistically significant peak levels at 6 months postinduction of endometriosis. We conclude from this study that sera miR-451a levels positively correlated with endometriotic lesion content and are significantly greater compared to sera levels in women without visible signs or symptoms of endometriosis. MicroRNA-451a may serve as a serum diagnostic marker for endometriosis.
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Abstract

We have previously demonstrated that human microRNA-451a (miR-451a) endometriotic lesion expression is significantly higher compared to that of the corresponding eutopic endometrium. The objective of the current study was to examine the relationship between lesion and serum content of miR-451a and to determine the utility of serum miR-451a in distinguishing between women with and without visible signs of endometriosis. Eighty-one participants were enrolled in this study, 41 with confirmed endo-metriosis and 40 without visible signs of endometriosis at laparoscopy (n = 20) or symptoms of endometriosis (pain, infertility n = 20). Experimental endometriosis was also induced in 8 baboons. Blood, endometriotic lesions, and eutopic endometrial samples were collected from women undergoing laparoscopy for surgical removal of endometriosis. Blood was also collected from control participants with no signs and symptoms associated with the disease as well as from baboons prior to, and then 1, 3, 6, 9, and 15 months postinduction of endometriosis. MicroRNA-451a was assessed by quantitative real-time polymerase chain reaction in all samples. In humans, serum miR-451a levels positively correlated with endometriotic lesion miR-451a content, and sera levels were significantly higher in these participants compared to controls. The area under the curve (AUC) for miR-451a was 0.8599. In baboons, serum miR-451a reached statistically significant peak levels at 6 months postinduction of endometriosis. We conclude from this study that sera miR-451a levels positively correlated with endometriotic lesion content and are significantly greater compared to sera levels in women without visible signs or symptoms of endometriosis. MicroRNA-451a may serve as a serum diagnostic marker for endometriosis. Similar content being viewed by others

References

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Semin Reprod Med. 2015;33(4):246–256. Smigielska-Czepiel K, van den Berg A, Jellema P, et al. Comprehensive analysis of miRNA expression in T-cell subsets of rheumatoid arthritis patients reveals defined signatures of naive and memory Tregs. Genes Immun. 2014;15(2):115–125. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Nothnick, W.B., Falcone, T., Joshi, N. et al. Serum miR-451a Levels Are Significantly Elevated in Women With Endometriosis and Recapitulated in Baboons (Papio anubis) With Experimentally-Induced Disease. Reprod. Sci. 24, 1195–1202 (2017). https://doi.org/10.1177/1933719116681519 Published: Issue date: DOI: https://doi.org/10.1177/1933719116681519

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endometriosis

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Endometriosis MicroRNAs Adult Animals Disease Endometriosis Female Humans MicroRNAs Middle Aged Papio anubis Young Adult

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