Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

Abstract

The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal weight PCOS either, increased visceral adipose tissue has been described. However, their role is still debated, as debated are the biochemical markers linked to obesity per se. Oxidative stress (OS) and low-grade inflammation (LGI) have recently been a matter of researcher attention; they can influence each other in a reciprocal vicious cycle. In this review, we summarize the main mechanism of radical generation and the link with LGI. Furthermore, we discuss papers in favor or against the role of obesity as the first pathogenetic factor, and show how OS itself, on the contrary, can induce obesity and insulin resistance; in particular, the role of GH-IGF-1 axis is highlighted. Finally, the possible consequences on vitamin D synthesis and activation on the immune system are briefly discussed. This review intends to underline the key role of oxidative stress and low-grade inflammation in the physiopathology of PCOS, they can cause or worsen obesity, insulin-resistance, vitamin D deficiency, and immune dyscrasia, suggesting an inverse interaction to what is usually considered.

Relation between Inflammation, Oxidative Stress, and Macronutrient Intakes in Normal and Excessive Body Weight Adolescent Girls with Clinical Features of Polycystic Ovary Syndrome

“…The relationship between childhood obesity and inflammation is also confirmed, but data on childhood obesity and OS are emerging [1,38]. Obesity induces chronic low-grade inflammation [11,12,38,39]. These processes are most likely related to the adipocyte's abnormal function and the dysregulation of adipocytokines secreted by adipose tissue [12,39,40].…”

“…Both disorders underlie many chronic conditions, including those related to diet [2,[5][6][7]. It seems that such a disease is polycystic ovary syndrome (PCOS) [8][9][10][11][12]. Hyperandrogenism, the hallmark of PCOS, is clinically manifested by acne, masculinization, and higher incidence of metabolic disorders such as insulin resistance (IR); dyslipidemia, mainly visceral obesity; arterial hypertension; and type 2 diabetes mellitus [13,14].…”

Polycystic Ovary Syndrome in Insulin-Resistant Adolescents with Obesity: The Role of Nutrition Therapy and Food Supplements as a Strategy to Protect Fertility

“…Inadequate intake and subsequent deficiencies of zinc, magnesium and selenium are involved in decreased secretion and/or activity of insulin, while their supplementation, in both diabetic and non-diabetic subjects, has shown HOMA-IR and fasting glucose improvements [136]. Both zinc and selenium are essential micronutrients for metabolism and regulate several enzymes involved in the production and neutralization of ROS [136]; therefore, they act as antioxidants counteracting the oxidative stress involved in PCOS and are probably significant in its pathogenesis [137]. Additionally, chromium (III) supplementation has been shown to effectively improve glucose tolerance by reducing IR and improving insulin-binding capacity and the number of receptors and insulin receptor enzymes by increasing insulin sensitivity, beta cell sensitivity and insulin internalization [136].…”

Rhamnocitrin Ameliorates Ovarian Fibrosis Via PPARγ/TGF-β1/Smad Pathway to Repair Ovarian Function in Polycystic Ovary Syndrome Rats Running Title：rhamnocitrin Ameliorates Ovarian Fibrosis in Polycystic Ovary Syndrome Rats

“…The pathophysiology of PCOS is quite complex, recently, low-grade in ammation and oxidative stress have been a matter of researcher attention [5]. Flavonoids are well known to be bioactive polyphenols that are associated with anti-in ammation and antioxidant effects due to their highly reactive oxygen radicals [6].…”