Abstract
Male fetal Leydig cells in the testis secrete androgen and insulin-like 3, determining the sexual differentiation. The abnormal development of fetal Leydig cells could lead to the reduction of androgen and insulin-like 3, thus causing the male reproductive tract anomalies in male neonates, including cryptorchidism and hypospadias. Environmental pollutants, such as phthalic acid esters (phthalates), can perturb the development and differentiated function of Leydig cells, thereby contributing to the reproductive toxicity in the male. Here, we review the epidemiological studies in humans and experimental investigations in rodents of various phthalates. Most of phthalates disturb the expression of various genes encoded for steroidogenesis-related proteins and insulin-like 3 in fetal Leydig cells and the dose-additive effects are exerted after exposure in a mixture.
Highlights
Reports of decline in sperm counts of human adult males over the past 60 years and the reproductive tract anomalies in new-born baby boys exposed to the chemicals in the environment have generated much public concern (Moline et al, 2000)
Vof these chemicals are phthalate esters, which are widely used in the plastic industry and they are credited with the inhibition of androgen synthesis activity because they suppress androgen-stimulated sexual differentiation in rodents (Akingbemi and Hardy, 2001; Sharpe, 2001)
This observation suggests that factors other than luteinizing hormone (LH) are important in the regulation of the production of testosterone in the fetal testis
Summary
Reports of decline in sperm counts of human adult males over the past 60 years and the reproductive tract anomalies in new-born baby boys exposed to the chemicals in the environment have generated much public concern (Moline et al, 2000). By acting as ligand-inducible transcription factors that activate or repress transcription of target genes, sex steroid hormone receptors control fundamental events in the embryonic development and sexual differentiation. Agonists and antagonists of the sex steroid hormone family of the nuclear transcription factors, androgen and estrogen receptors, are associated with the reproductive tract anomalies. Prenatal testosterone or dihydrotestosterone exposure stimulates sexual differentiation via promoting the generation of male reproductive tracts and postnatally they promote the development of the male sexual characteristics and maintain the male phenotype in adulthood (Figure 1). Testosterone is converted to estradiol by the aromatase in the brain (Balthazart and Foidart, 1993; Callard et al, 1993; Roselli and Resko, 1993), resulting in activation of estrogen receptor-mediated pathways associated with male sexual behavior (Meisel and Sachs, 1994).
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