Exposure to Phytoestrogens in the Perinatal Period Affects Androgen Secretion by Testicular Leydig Cells in the Adult Rat

Abstract

The use of soy-based products in the diet of infants has raised concerns regarding the reproductive toxicity of genistein and daidzein, the predominant isoflavones in soybeans with estrogenic activity. Time-bred Long-Evans dams were fed diets containing 0, 5, 50, 500, or 1000 ppm of soy isoflavones from gestational d 12 until weaning at d 21 postpartum. Male rats in all groups were fed soy-free diets from postnatal d 21 until 90 d of age. The mean +/- SD concentration of unconjugated (i.e. biologically active) genistein and daidzein in serum from the group of dams maintained on the diet containing the highest amount of isoflavones (1000 ppm) were 17 +/- 27 and 56 +/- 30 nM, respectively, at d 21 postpartum. The concentrations were considerably greater in male offspring (genistein: 73 +/- 46 nM; daidzein: 106 +/- 53 nM). Although steroidogenesis was decreased in individual Leydig cells, male rats from the highest exposure group (1000 ppm diet) exhibited elevated serum levels of the sex steroid hormones androsterone at 21 d (control: 15 +/- 1.5 vs.28 +/- 3.5 ng/ml; P < 0.05) and testosterone at 90 d of age (control: 7.5 +/- 1 vs.17 +/- 2 ng/ml; P < 0.05). Testosterone secretion by immature Leydig cells, isolated from 35-d-old male rats, decreased on exposure to 0.1 nm genistein in vitro (control: 175 +/- 5 vs. 117 +/- 3 ng/10(6) cells per 24 h; P < 0.05), indicative of direct phytoestrogen action. Thus, phytoestrogens have the ability to regulate Leydig cells, and additional studies to assess potential adverse effects of dietary soy-based products on reproductive tract development in neonates are warranted.

Effects of genistein and equol on human and rat testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 activities

“…The levels of genistein affecting steroidogenic enzyme activity in the present study approximate levels that have been measured in individuals consuming soy products [7]. The present results are in agreement with our previous findings of genistein acting directly in rat Leydig cells to cause inhibition of androgen biosynthesis [8,9]. Changes in androgen biosynthesis, occasioned by exposure to endocrine disruptors, have the potential to interfere with androgen-stimulated reproductive tract development [19,20].…”

“…These findings, along with previous observations indicating that genistein interferes with LH signalling in rat Leydig cells [8,9], suggest that genistein exerts multiple mechanisms to affect testicular steroidogenesis. LH binding stimulates steroidogenic enzyme activity, which enhances androgen biosynthesis.…”

“…Similarly, serum genistein levels in the adult can be as high as 10 µmol L -1 immediately following consumption of a phytoestrogen-rich meal [7]. Moreover, previous studies showed that genistein has the ability to suppress testosterone production in the rat Leydig cells in vitro and in vivo [8,9].…”

Effects of daidzein on testosterone secretion in cultured immature mouse testis

“…Male rats were given different concentrations of soy isoflavones from gestational day 12 until weaning at day 21 postpartum. The results showed that low dose increased serum and cultured Leydig cell testosterone levels and high doses decreased serum testosterone production at day 21 postpartum [8]. Recent studies have shown that highdose soy isoflavones administered to rats from prenatal life to sexual maturity induced changes in the morphology of the seminiferous epithelium and significantly decreased testicular testosterone concentration.…”

Endocrine milieu and erectile dysfunction: is oestradiol–testosterone imbalance, a risk factor in the elderly?

“…In animal studies, correlations have already been made between phytoestrogen intake, androgen decrease and ED. 37,[65][66][67] In the light of this evidence, it is important to bridge the lacunae in the understanding of this sexual health threat to men through well-designed epidemiological and prevalence studies.…”