In utero-exposed di(n-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats
| Autor: | Hiroyuki Takahashi, Masao Asari, Yuya Okayama, Michael F. Wempe, Masahiro Ikegami, Shin Wakui, Masaya Motohashi, Tomoko Mutou, Norio Kansaku |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Leydig cell Dibutyl phthalate Cholesterol side-chain cleavage enzyme Steroidogenic acute regulatory protein 010501 environmental sciences Biology Toxicology 01 natural sciences SCARB1 03 medical and health sciences chemistry.chemical_compound Dose–response relationship 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry In utero Internal medicine medicine Testosterone 0105 earth and related environmental sciences |
| Zdroj: | The Journal of Toxicological Sciences. 41:195-206 |
| ISSN: | 1880-3989 0388-1350 |
| DOI: | 10.2131/jts.41.195 |
| Popis: | Female pregnant Sprague-Dawley rats were intragastrically (ig) administered di(n-butyl) phthalate (DBP) at four doses (0, 10, 50 and 100 mg/kg) during gestation days (GD) 12-21 (n = 5 per group). The age-related morphological changes of Leydig cell mitochondrion (LC-Mt) and testosterone biosynthesis enzymes/associated genes/proteins expression levels were investigated. As compared to the control (no DBP), the 10 mg, and 50 mg DBP dose groups, the 100 mg DBP dose group at weeks 5 and 7 showed a significant amount of small LC-Mt. Thereafter, from weeks 9 to 17, the LC-Mt size and quantity in the 100 mg DBP dose group increased and became statistically similar to the other dose groups; hence, dose and time-dependent LC-Mt changes were observed. Throughout the study, the 100 mg DBP dose group had significantly lower testosterone levels. In addition, the 100 mg DBP dose group displayed lower StAR (StAR, steroidogenic acute regulatory protein) and P450scc (CYP11a1, cholesterol side-chain cleavage enzyme) levels at weeks 5 and 7, but they became statistically similar to all other dose groups at weeks 9 to 17; in contrast, the SR-B1 (Sarb1, scavenger receptor class B member 1) levels were similar for all DBP dose groups. The rats in utero 100 mg DBP /kg/day (GD 12-21) exposure results from this study indicate a dose-dependent, age-related morphological change in LC-Mt which are linked to reductions in testosterone biosynthesis genes / proteins expression, specifically StAR and P450scc. |
| Databáze: | OpenAIRE |
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