title: Antagonistic effects of a mixture of low-dose nonylphenol and di-n-butyl phthalate (monobutyl phthalate) on the Sertoli cells and serum reproductive hormones in prepubertal male rats in vitro and in vivo.
abstract: The estrogenic chemical nonylphenol (NP) and the antiandrogenic agent di-n-butyl phthalate (DBP) are regarded as widespread environmental endocrine disruptors (EDCs) which at high doses in some species of laboratory animals, such as mice and rats, have adverse effects on male reproduction and development. Given the ubiquitous coexistence of various classes of EDCs in the environment, their combined effects warrant clarification. In this study, we attempted to determine the mixture effects of NP and DBP on the testicular Sertoli cells and reproductive endocrine hormones in serum in male rats based on quantitative data analysis by a mathematical model. In the in vitro experiment, monobutyl phthalate (MBP), the active metabolite of DBP, was used instead of DBP. Sertoli cells were isolated from 9-day-old Sprague-Dawley rats followed by treatment with NP and MBP, singly or combined. Cell viability, apoptosis, necrosis, membrane integrity and inhibin-B concentration were tested. In the in vivo experiment, rats were gavaged on postnatal days 23-35 with a single or combined NP and DBP treatment. Serum reproductive hormone levels were recorded. Next, Bliss Independence model was employed to analyze the quantitative data obtained from the in vitro and in vivo investigation. Antagonism was identified as the mixture effects of NP and DBP (MBP). In this study, we demonstrate the potential of Bliss Independence model for the prediction of interactions between estrogenic and antiandrogenic agents.
authors.affiliation: Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Zou
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Qian
authors.affiliation: Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
authors.affiliation: Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000494:pharmacology*; D028322:Inhibin-beta Subunits / Q000378:metabolism; D008297:Male; D015233:Models, Statistical; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D010636:Phenols / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010795:Phthalic Acids / Q000494:pharmacology*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D010636:Phenols; D010795:Phthalic Acids; C025256:nonylphenol; D028322:Inhibin-beta Subunits; C028577:monobutyl phthalate