Induction of spermatogenic cell apoptosis in prepubertal rat testes irrespective of testicular steroidogenesis: a possible estrogenic effect of di(n-butyl) phthalate

Abstract

Although di(n-butyl) phthalate (DBP), a suspected endocrine disruptor, induces testicular atrophy in prepubertal male rats, whether it exerts estrogenic activity in vivo remains a matter of debate. In the present study, we explored the estrogenic potency of DBP using 3-week-old male rats, and then examined the relationship between estrogen-induced spermatogenic cell apoptosis and testicular steroidogenesis. Daily exposure to DBP for 7 days caused testicular atrophy due to loss of spermatogenic cells, whereas testicular steroidogenesis was almost the same with the control values. A single exposure of DBP decreased testicular steroidogenesis in addition to decreasing the level of serum LH at 3 h after DBP treatment, with an extremely high incidence of apoptotic spermatogenic cells at 6 h after administration. To elucidate the estrogenic activity of DBP, we carried out an inhibition study using pure antiestrogen ICI 182,780 (ICI) in a model of spermatogenic cell apoptosis induced by DBP or estradial-3-benzoate (EB). Although both the DBP-and EB-treated groups showed a significant increase in spermatogenic cell apoptosis, ICI pretreatment significantly decreased the number of apoptotic spermatogenic cells in these two groups. In contrast, testicular steroidogenesis and serum FSH were significantly reduced in all the treated groups, even in the DBPCICI and EBCICI groups. Taken together, these findings led us to conclude that estrogenic compounds such as DBP and EB induce spermatogenic cell apoptosis in prepubertal rats, probably by activating estrogen receptors in testis, and that reduction in testicular steroidogenic function induced by estrogenic compounds is not associated with spermatogenic cell apoptosis.

Retraction: Quantitative morphometric analysis of vimentin filaments in Sertoli cells of rats after <i>in utero</i> DBP exposure

“…It has been reported that exposure of 3-week-old rats to di(2-ethlhexl)phthalate (DEHP) caused disruption and collapse of Vim microfilaments in Sertoli cells (Erkekoglu et al, 2012). Moreover, the volume of Vim microfilaments in Sertoli cells was reported to be reduced in young rats after exposure to other phthalates including DEHP, mono(2-ethylhexyl)phthalate (MEHP), and DBP (Richburg et al, 1999;Tay et al, 2007;Alam et al, 2010). Although one study concerning the alteration of Vim in Sertoli cells after in utero DBP exposure was reported, it was limited to five postnatal days (Kleymenova et al, 2005).…”

Di-n-Butyl Phthalate (DBP) Exposure Induces Oxidative Damage in Testes of Adult Rats

“…The observed reduction in the weight of testes is due to the decreased number of germ cells and elongated spermatids in the testes [Aly et al 2009], which is consistent with the results of testicular histological changes. DBP caused regressive histological changes in the seminiferous tubules which supports the results of other authors [Alam et al 2010;Xiaofeng et al 2009]. Seminiferous tubule atrophy and a decreased number of spermatogenic cells were morphologic indicators of spermatogenesis failure [Park et al 2002].…”

“…Although there is insufficient data for DBP effects on human reproduction, some studies in rodents have reported the influence of DBP on the male reproductive system [Alam et al 2010;Scarano et al 2009;Hoshi and Ohtsuka 2009]. To date, however, the mechanisms of reproductive toxicology of DBP are still unclear and need to be further studied.…”

Atypical Leydig Cell Hyperplasia in Adult Rats with Low T and High LH Induced by Prenatal Di(n-butyl) Phthalate Exposure

“…However, after oral administration of DBP to rats, 90 to 96% of administered dose is excreted in urine within 48 hr (Hoppin et al 2002), but the prenatal exposed DBP exhibits abnormal gonocytes development (Alam et al 2010). Moreover, prenatal DBP exposures induce testicular dysgenesis in adult rat offspring, but this testicular toxicity is not considered to be the direct influence of prenatal exposed DBP and/or its metabolites (Mylchreest et al 2002).…”