High-Frequency Electrical Modulation of the Superior Ovarian Nerve as a Treatment of Polycystic Ovary Syndrome in the Rat.

Victor Pikov,Arun Sridhar,Hernan E Lara

doi:10.3389/fphys.2018.00459

Abstract

The polycystic ovary syndrome (PCOS) is the most prevalent ovarian pathology in women, with excessive sympathetic activity in the superior ovarian nerve (SON) playing an important role in inducing the PCOS symptoms in the rats and humans. Our previous studies have shown that surgical transection of the SON can reverse the disease progression, prompting us to explore the effect of the kilohertz frequency alternating current (KHFAC) modulation as a method of reversible non-surgical suppression of the nerve activity in the rodent model of PCOS. 56 animals were randomly allocated to three groups: the Control group (n = 18), the PCOS group (n = 15), and the PCOS + KHFAC group (n = 23). The physiological, anatomical, and biochemical parameters of ovarian function were evaluated during the progression of the experimentally-induced PCOS and during long-term KHFAC modulation applied for 2–3 weeks. The KHFAC modulation has been able to reverse the pathological changes in assessed PCOS parameters, namely the irregular or absent estrous cycling, formation of ovarian cysts, reduction in the number of corpora lutea, and ovarian norepinephrine concentration. The fertility capacity was similar in the PCOS and the PCOS + KHFAC groups, indicating the safety of KHFAC modulation approach. In summary, these results suggest that the KHFAC modulation approach of suppressing the SON activity could become a useful treatment modality for PCOS and potentially other pathological ovarian conditions.

Highlights

Polycystic ovary syndrome (PCOS) is the most common ovarian pathology during reproductive age; it is characterized by hyperandrogenism and the polycystic ovary phenotype (Azziz et al, 2009)
In three PCOS + kilohertz frequency alternating current (KHFAC) animals at Huntington Medical Research Institutes (HMRI) that were subjected to a 3-week-long KHFAC modulation, normal estrous cycling was restored at 7–17 days after the initiation of KHFAC
This study evaluated several physiological, anatomical, and biochemical parameters of ovarian function after the experimentally-induced PCOS and long-term KHFAC modulation of the superior ovarian nerve (SON) in the rodents

Summary

Introduction

Polycystic ovary syndrome (PCOS) is the most common ovarian pathology during reproductive age; it is characterized by hyperandrogenism and the polycystic ovary phenotype (Azziz et al, 2009). Current treatments of PCOS, such as estrogen receptor modulators, gonadotropins, laparoscopic ovarian drilling, weight loss and exercise, focus on the symptoms rather than the underlying cause and are moderately effective. The SON fibers predominantly innervate the secretory components of the ovary, i.e., interstitial glands and follicles, whereas the ovarian plexus nerve fibers are mostly perivascular (Lawrence and Burden, 1980). The innervation of the gland has been shown to be involved in the regulation of ovary specific functions, such as steroidogenesis and early follicular development (Lara et al, 2002; Greiner et al, 2005) by activating B-adrenergic receptors present in cells of the ovarian follicle

Methods

Results

Conclusion