Abstract
The phytoestrogen genistein (GEN) may interfere with permanent morphological changes in the brain circuits sensitive to estrogen. Due to the frequent use of soy milk in the neonatal diet, we aimed to study the effects of early GEN exposure on some physiological and reproductive parameters. Mice of both sexes from PND1 to PND8 were treated with GEN (50 mg/kg body weight, comparable to the exposure level in babies fed with soy-based formulas). When adult, we observed, in GEN-treated females, an advanced pubertal onset and an altered estrous cycle, and, in males, a decrease of testicle weight and fecal testosterone concentration. Furthermore, we observed an increase in body weight and altered plasma concentrations of metabolic hormones (leptin, ghrelin, triiodothyronine) limited to adult females. Exposure to GEN significantly altered kisspeptin and POMC immunoreactivity only in females and orexin immunoreactivity in both sexes. In conclusion, early postnatal exposure of mice to GEN determines long-term sex-specific organizational effects. It impairs the reproductive system and has an obesogenic effect only in females, which is probably due to the alterations of neuroendocrine circuits controlling metabolism; thus GEN, should be classified as a metabolism disrupting chemical.
Highlights
IntroductionGEN is produced by many plants, is highly present in Leguminosae species, and, due to its estrogenic activity, is considered a phytoestrogen [1]
Genistein (GEN; 40,5,7-trihydroxyisoflavone) is an isoflavonoid compound
Vaginal opening (VO) is one of the parameters employed to evaluate the potential effects of endocrine disrupting chemicals on puberty onset in rodents [53]
Summary
GEN is produced by many plants, is highly present in Leguminosae species, and, due to its estrogenic activity, is considered a phytoestrogen [1]. The main sources of GEN, in our diet, are soybeans and soy-based foods. Most foods contain a small quantity of isoflavones, but when consumed regularly and from various sources, they can reach a cumulative dose that can contribute to long-term effects [2]. Phytoestrogens, including GEN, have been generally associated with beneficial effects, i.e., obesity and diabetes [3], menopause [4], cancer [5], and hypertension associated to metabolic syndrome [6]; many studies suggest that phytoestrogens are harmful to human health [7,8]. In addition to soy-based infant formulas many soy-based foods are prepared for babies [9,10]. Sex-specific alterations were reported in several neuronal populations, including hypothalamic and amygdaloid circuits containing many gonadal hormone-sensitive neurons [11,12,13,14,15,16]
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