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 DBP+ICI and EB+ICI 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.

• Authors: Mohammad Shah Alam, Seiichiroh Ohsako, Takashi Matsuwaki, Xiao Bo Zhu, Naoki Tsunekawa, Yoshiakira Kanai, Hideko Sone, Chiharu Tohyama, Masamichi Kurohmaru
• Journal: Reproduction (Cambridge, England) (Reproduction) Vol. 139 Issue 2 Pg. 427-37 (Feb 2010) ISSN: 1741-7899 [Electronic] England
• PMID: 19903717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endocrine Disruptors
• Estrogen Antagonists
• Estrogens
• estradiol 3-benzoate
• Dibutyl Phthalate
• Fulvestrant
• Testosterone
• Estradiol
• Luteinizing Hormone
• Follicle Stimulating Hormone

Topics

• Animals
• Apoptosis (drug effects)
• Atrophy
• Dibutyl Phthalate (toxicity)
• Dose-Response Relationship, Drug
• Endocrine Disruptors (toxicity)
• Estradiol (analogs & derivatives, pharmacology, toxicity)
• Estrogen Antagonists (pharmacology)
• Estrogens (toxicity)
• Follicle Stimulating Hormone (blood)
• Fulvestrant
• Leydig Cells (drug effects, pathology)
• Luteinizing Hormone (blood)
• Male
• Rats
• Sexual Maturation
• Spermatogenesis (drug effects)
• Testis (drug effects, growth & development, metabolism, pathology)
• Testosterone (biosynthesis)
• Time Factors