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. 2019 Oct;26(10):1343-1350.
doi: 10.1177/1933719118765971. Epub 2018 Mar 27.

Serum MicroRNA Biomarkers Regulated by Simvastatin in a Primate Model of Endometriosis

Emine Cosar  1 , Ramanaiah Mamillapalli  1 , Irene Moridi  1 , Antoni Duleba  2 , Hugh S Taylor  1
Affiliations

Serum MicroRNA Biomarkers Regulated by Simvastatin in a Primate Model of Endometriosis

Emine Cosar et al. Reprod Sci. 2019 Oct.

Abstract

Endometriosis is a chronic inflammatory and estrogen-dependent disease that causes pain and infertility in reproductive-aged women. Due to the delay in diagnosis, there is a pressing need for accurate biomarkers. Detection of serum noncoding RNA molecules such as microRNAs (miRNAs) shows promise as a noninvasive diagnostic strategy; we previously identified miRNAs that are highly sensitive and specific biomarkers for the disease. In this study, we investigate the expression of these miRNAs in a nonhuman primate model of endometriosis. As part of a pilot study evaluating simvastatin for the treatment of endometriosis, the disease was induced in 16 baboons by induction laparoscopy and the animals were divided into 2 groups. One group was treated with simvastatin for 90 days, while the second group received vehicle only. Endometriosis was evaluated after 3 months by laparoscopy. Serum samples were analyzed for 9 circulating miRNAs using quantitative real time-polymerase chain reaction, focusing on the miRNAs we found to be dysregulated in human endometriosis. In the simvastatin-treated endometriosis group, levels of miR-150-5p and miR-451a were decreased, while miR-3613-5p levels were increased compared to the untreated endometriosis group. The changes in circulating miRNA expression patterns parallel our previous results in human patients and show that specific miRNAs correlate with endometriosis severity and reverted toward control expression levels after simvastatin treatment. This is the first report showing serum miRNA expression normalized in response to endometriosis treatment, supporting the potential for this class of biomarkers to be used both to diagnose endometriosis and to monitor its progression and response to therapy.

Keywords: baboons; biomarker; endometriosis; miRNAs; simvastatin; statins.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Average total volume of disease (combined volume of lesions and adhesions) per baboon in simvastatin-treated baboons (n = 8) versus controls (n = 8). Includes all types of lesions and adhesions (see methods). Data are expressed as mean ± SEM. *P < .05, using an unpaired t test with Welch correction. Endometriosis indicates endometriosis.
Figure 2.
Figure 2.
Differential expression of circulating microRNAs (miRNAs) in response to simvastatin treatment of endometriosis in baboons. Serum was collected from simvastatin-treated baboons with endometriosis as well as untreated controls at 3-month postinduction of endometriosis. Expression levels were determined by quantitative real time-polymerase chain reaction (qRT-PCR) and normalized to U6 expression levels. Error bars represent the mean ± SEM of 3 individual experiments, each in triplicate (n = 8 baboons per group). *P < .05, using an unpaired t test with Welch correction.
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