Prenatal exposure to DEHP induces premature reproductive senescence in male mice
| Autor: | Saniya Rattan, Emily Brehm, Jodi A. Flaws, Radwa Barakat, Mohamed E. Abosalum, Po Ching Patrick Lin, Rex A. Hess, Igor F. Canisso, CheMyong Ko |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Administration Oral Prenatal Phthalate Exposure and Reproductive Senescence Apoptosis Endocrine Disruptors 010501 environmental sciences Toxicology 01 natural sciences Mice chemistry.chemical_compound Plasticizers Pregnancy Testis Testosterone Epididymis Estradiol Phthalate Aging Premature Organ Size medicine.anatomical_structure Endocrine disruptor Prenatal Exposure Delayed Effects Gestation Female endocrine system medicine.medical_specialty Offspring Asthenozoospermia Andrology 03 medical and health sciences Reproductive senescence Diethylhexyl Phthalate Internal medicine Animals Outbred Strains medicine Animals Infertility Male 0105 earth and related environmental sciences Dose-Response Relationship Drug business.industry Luteinizing Hormone medicine.disease Survival Analysis 030104 developmental biology Endocrinology chemistry business Corn oil |
| Zdroj: | Toxicological Sciences. :kfw248 |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kfw248 |
| Popis: | Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate, and it is an endocrine-disrupting chemical. This study tested a hypothesis that prenatal exposure to DEHP lays the foundation for premature gonadal dysfunction and subsequent reproductive senescence in male mice. Pregnant female CD-1 mice were orally dosed with vehicle control (tocopherol-stripped corn oil) or with 20 μg/kg/day, 200 μg/kg/day, 500 mg/kg/day, or 750 mg/kg/day of DEHP from gestational day 11 to birth. Overall, the prenatal DEHP exposure did not cause any overt physical health problems in male offspring, as no significant differences in their body nor gonadal weight were seen up to the age of 23 months. However, an age- and dose-dependent gonadal dysfunction was observed. As early as 7 months of age, the 750 mg/kg/day group of mice exhibited significantly reduced fertility. At 19 months of age, 86% of the 750 mg/kg/day mice became infertile, whereas only 25% of the control mice were infertile. At this age, all of the DEHP-exposed mice had lower serum testosterone levels, higher serum estradiol levels, and higher LH levels compared with control mice. Histological evaluations showed that mice prenatally exposed to DEHP displayed a wide array of gonadal and epididymal abnormalities such as increased germ cell apoptosis, degenerative seminiferous tubules, oligozoospermia, asthenozoospermia, and teratozoospermia in comparison to age-matching control mice. In summary, this study shows that prenatal exposure to DEHP induces premature reproductive senescence in male mice. |
| Databáze: | OpenAIRE |
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