Abstract
Humans are inevitably exposed to ubiquitous phthalate esters (PAEs). In utero exposure to di-n-butyl phthalate (DBP) induces abnormal development of the testis and reproductive tract in male offspring, which correspond closely with the human condition of testicular dysgenesis syndrome (TDS)-like syndrome. However, the underlying mechanisms have not been elucidated in detail. In this study, pregnant rats were orally exposed to either corn oil (controls) or DBP at three different doses by gavage during Gestational Days 12.5–21.5. Pathological examinations were performed for toxicity evaluation. Proliferation and apoptosis related proteins (ras related dexamethasone induced 1 (Rasd1), mitogen-activated protein kinase kinases1/2 (MEK1/2), Bcl-2, and Bax) were measured for mechanisms exploration. The results showed that different doses of DBP caused male developmental and reproductive toxicity in rats, including the decrease of anogenital distance (AGD), the histological damage of testis, and apoptosis of seminiferous tubule cells. Our data suggested that DBP played chronic and continuous toxic roles on male reproductive system by disrupting expression of Rasd1 and MEK1/2 as well as Bcl-2/Bax ratio. Further research is warranted.
Highlights
Over the past decades, male reproductive problems, such as poor spermatogenesis, testicular cancer, hypospadias, and cryptorchidism, are widespread in all parts of the World [1]
testicular dysgenesis syndrome (TDS) might result from genetic mutations, recent evidence suggested that it most often was related to environmental exposures of the fetal testis; for example, many of the characteristics of the syndrome could be reproduced in the male offspring of female rats exposed to chemicals with estrogenic or anti-androgenic properties during pregnancy, such as di-n-butyl phthalate (DBP) [4]
DBP was dosed by gavage at 50, 250, and 500 mg/kg/day (GD 12.5–21.5) in pregnant rats
Summary
Male reproductive problems, such as poor spermatogenesis, testicular cancer, hypospadias, and cryptorchidism, are widespread in all parts of the World [1]. Evidence was presented that several adult male reproductive problems arise in utero and were signs of testicular dysgenesis syndrome (TDS) [2,3]. Phthalate esters (PAEs) are industrial chemicals used primarily as plasticizers to impart flexibility to polyvinylchloride plastics They are present in a wide variety of products, such as children’s toys, cosmetics, personal care products, food contact applications, and medical devices [5,6]. They are metabolized in the gut to the corresponding monoester and alcohol [7,8], with toxicity ascribed to the monoester metabolite [9,10]
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