Soy but not bisphenol A (BPA) induces hallmarks of polycystic ovary syndrome (PCOS) and related metabolic co-morbidities in rats

Abstract

Polycystic ovarian syndrome (PCOS) is the most common female endocrine disorder with a prevalence as high as 8–15% depending on ethnicity and the diagnostic criteria employed. The basic pathophysiology and mode of inheritance remain unclear, but environmental factors such as diet, stress and chemical exposures are thought to be contributory. Developmental exposure to endocrine disrupting compounds (EDCs) have been hypothesized to exacerbate risk, in part because PCOS hallmarks and associated metabolic co-morbidities can be reliably induced in animal models by perinatal androgen exposure. Here we show that lifetime exposure to a soy diet, containing endocrine active phytoestrogens, but not developmental exposure (gestational day 6 – lactational day 40) to the endocrine disrupting monomer Bisphenol A (BPA), can induce key features of PCOS in the rat; results which support the hypothesis that hormonally active diets may contribute to risk when consumed throughout gestation and post-natal life.

Comparison of endpoints relevant to toxicity assessments in 3 generations of CD-1 mice fed irradiated natural and purified ingredient diets with varying soy protein and isoflavone contents

“…While there were no significant diet effects on ovary weights, there was a higher incidence of gross ovarian cysts in the three low isoflavone diets compared to the NIH-41 diet. Patisaul et al (2014) recently reported an increased incidence of cystic follicles in Wistar rats fed a soy meal containing diet.…”

Evidence-based adverse outcome pathway approach for the identification of BPA as en endocrine disruptor in relation to its effect on the estrous cycle

“…Alteration of kisspeptin expression -In vitro: Klenke et al, 2016-In vivo: Cao et al, 2012Navarro et al, 2009;Xi et al, 2011;Naulé et al, 2014;Kurian et al, 2015 Alteration in GnRH and/or LH secretion -In vivo: Monje et al, 2010;Fernández et al, 2009;Viega-Lopez et al, 2014;Kurian et al, 2015 Alteration of estrous cyclicity -In vivo: Honma et al, 2002;Nikaido et al, 2004;Wang et al, 2014a;Rubin et al, 2001;Mendoza-Rodríguez et al, 2011;Patisaul et al, 2014;Delclos et al, 2014;Nah et al, 2011;Adewale et al, 2009;Fernández et al, 2009;Zaid et al, 2014 Table 8 provides an overview of the critical elements in the identification of an endocrine disruptor and how they are fulfilled for alteration of estrous cycle by BPA.…”

Soy but not bisphenol A (BPA) or the phytoestrogen genistin alters developmental weight gain and food intake in pregnant rats and their offspring

“…In a prior study with a similar design, we showed that a soy-rich diet (Purina 5001) generating approximately 20 ng/ml (74 nM) free GEN levels in the dams [50], promoted early VO, weight gain, elevated baseline glucose levels and increased area under the curve in the classic glucose challenge test [78]. Isoflavone levels in the custom diet for the present study were 400 mg/kg, and produced dam serum GEN levels in the range of 2.8–31 ng/mL.…”