Phytoestrogens are naturally occurring plant-derived phytochemicals, whose common biological roles are to protect plants from stress or to act as part of a plant’s defense mechanism. Although composed of a wide group of nonsteroidal compounds of diverse structure, phytoestrogens have been shown to bind estrogen receptors and to behave as weak agonist/antagonist in both animals and humans. Phytoestrogens include mainly isoflavones (IF), coumestans, and lignans. These compounds are known to be present in fruits, vegetables, and whole grains commonly consumed by humans. IF are found in legumes - mainly soybeans - whereas flaxseed is a major source of lignans, and coumestans are significantly present in clover, alfalfa and soybean sprouts. 8-Prenyl flavonoids are common in vegetables. Bioavailability of IF requires an initial hydrolysis of the sugar moiety by intestinal betaglucosidases to allow the following uptake by enterocytes and the flow through the peripheral circulation. Following absorption, IF are then reconjugated mainly to glucuronic acid and to a lesser degree to sulphuric acid. Gut metabolism seems key to the determination of the potency of action. Several epidemiological studies correlated high dose consumptions of soy IF with multiple beneficial effects on breast and prostate cancers, menopausal symptoms, osteoporosis, atherosclerosis and stroke, and neurodegeneration. For the relief of menopausal symptoms a consumption of 60 mg aglycones/day has been suggested; for cancer prevention a consumption between 50 and 110 mg aglycones/day is considered beneficial to reduce risks of breast, colon and prostate cancer; to decrease cardiovascular risk a minimum intake of 40-60 mg aglycones/day, together with about 25 g of soy protein has been suggested. For improvement in bone mineral density, 60-100 mg aglycones/day for a period of at least 6-12 months could be beneficial.

Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including potential effects on the endocrine system The present pilot study examine whether exposure to GBHs at the dose of glyphosate considered to be “safe” (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero life, affect the development and endocrine system across different life stages in Sprague Dawley (SD) rats. Glyphosate alone and Roundup Bioflow, a commercial brand of GBHs, were administered in drinking water at 1.75 mg/kg bw/day to F0 dams starting from the gestational day (GD) 6 (in utero) up to postnatal day (PND) 120. After weaning, offspring were randomly distributed in two cohorts: 8 M + 8F/group animals belonging to the 6-week cohort were sacrificed after puberty at PND 73 ± 2; 10 M + 10F/group animals belonging to the 13-week cohort were sacrificed at adulthood at PND 125 ± 2. Effects of glyphosate or Roundup exposure were assessed on developmental landmarks and sexual characteristics of pups. In pups, anogenital distance (AGD) at PND 4 was statistically significantly increased both in Roundup-treated males and females and in glyphosate-treated males. Age at first estrous (FE) was significantly delayed in the Roundup-exposed group and serum testosterone concentration significantly increased in Roundup-treated female offspring from the 13-week cohort compared to control animals. A statistically significant increase in plasma TSH concentration was observed in glyphosate-treated males compared with control animals as well as a statistically significant decrease in DHT and increase in BDNF in Roundup-treated males. Hormonal status imbalances were more pronounced in Roundup-treated rats after prolonged exposure. The present pilot study demonstrate that GBHs exposure, from prenatal period to adulthood, induced endocrine effects and altered reproductive developmental parameters in male and female SD rats. In particular, it was associated with androgen-like effects, including a statistically significant increase of AGDs in both males and females, delay of FE and increased testosterone in female.

The role of endocrine disruptors (EDs) in the human prostate gland is an overlooked issue even though the prostate is essential for male fertility. From experimental models, it is known that EDs can influence several molecular mechanisms involved in prostate homeostasis and diseases, including prostate cancer (PCa), one of the most common cancers in the male, whose onset and progression is characterized by the deregulation of several cellular pathways including androgen receptor (AR) signaling. The prostate gland essentiality relies on its function to produce and secrete the prostatic fluid, a component of the seminal fluid, needed to keep alive and functional sperms upon ejaculation. In physiological condition, in the prostate epithelium the more-active androgen, the 5α-dihydrotestosterone (DHT), formed from testosterone (T) by the 5α-reductase enzyme (SRD5A), binds to AR and, upon homodimerization and nuclear translocation, recognizes the promoter of target genes modulating them. In pathological conditions, AR mutations and/or less specific AR binding by ligands modulate differently targeted genes leading to an altered regulation of cell proliferation and triggering PCa onset and development. EDs acting on the AR-dependent signaling within the prostate gland can contribute to the PCa onset and to exacerbating its development.