Effect of Myrcene on Th17/Treg Balance and Endocrine Function in Autoimmune Premature Ovarian Insufficiency Mice through the MAPK Signaling Pathway

Abstract

Background: Premature ovarian insufficiency (POI) is a defect of ovarian functions in women younger than 40 years old. Although a large number of studies have focused on investigating autoimmune POI, its detailed pathogenesis is still largely unknown. Several studies have indicated that Myrcene exerted a part in the biological processes of various diseases. Nonetheless, whether Myrcene could influence the development of autoimmune POI remains to be elucidated.

Methods: POI model was established by injecting zona pellucida glycoprotein 3 (pZP3). Hematoxylin and eosin (H&E) staining was applied to evaluate the pathological features of ovarian tissues. Enzymelinked immunosorbent assay (ELISA) was used for assessing the concentrations of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and interleukin (IL)-17. Flow cytometry analysis was conducted for assessing the balance of Th17/Treg cells.

Results: The results showed that decreased levels of body weight, ovarian weight and ovarian index were reversed by Myrcene in POI model mice. The estrous cycles in mice were extended in pZP3 mice and Myrcene administration restored it to normal. The reduced number of primordial, primary, and secondary follicles as well as the increased number of atretic follicles in POI mice were offset by Myrcene administration. Moreover, Myrcene could modulate the Th17/Treg balance in autoimmune POI. Besides, Myrcene suppressed the MAPK signaling pathway in pZP3 mice.

Conclusion: Myrcene regulated the Th17/Treg balance and endocrine function in autoimmune POI mice through the MAPK signaling pathway, which might provide a reference for improving the treatment of autoimmune POI.

Keywords: MAPK pathway; Myrcene; Th17/Treg balance; autoimmune premature ovarian insufficiency; endocrine function; pZP3.