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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
In Utero Exposure to Di( n-butyl)phthalate Induces Morphological and Biochemical Changes in Rats Postpuberty
Yuya Okayama1, Shin Wakui1,2, Michael F Wempe3
11 Department of Toxicology, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
Insights
In utero exposure to di(n-butyl)phthalate (DBP) significantly increased Sertoli cell proliferation in male rats postpuberty. This phthalate exposure also led to decreased testosterone and increased follicle-stimulating hormone (FSH) levels.
Area of Science:
- Reproductive Toxicology
- Developmental Biology
- Endocrinology
Background:
- Phthalates are endocrine-disrupting chemicals with known reproductive toxicity.
- Di(n-butyl)phthalate (DBP) exposure during critical developmental windows can impact male reproductive health.
- Sertoli cells play a crucial role in spermatogenesis and testicular development.
Purpose of the Study:
- To investigate the long-term effects of in utero di(n-butyl)phthalate (DBP) exposure on male offspring.
- To examine morphological and cellular alterations in Sertoli cells from postpuberty to adulthood.
- To assess the impact of DBP on reproductive hormone levels.
Main Methods:
- Pregnant Sprague-Dawley rats were administered DBP (100 mg/kg/day) from gestation days 12 to 21.
- Male offspring were assessed at 7, 9, 14, and 17 weeks of age.
- Evaluated parameters included body and testis weights, seminiferous tubule morphology, Sertoli cell proliferation (BrdU-positive cells), and serum hormone levels (testosterone and FSH).
Main Results:
- No significant differences in testicular weight/body weight ratios or seminiferous tubule morphology were observed at weeks 7 and 9.
- At weeks 14 and 17, DBP-exposed offspring showed statistically significant increases in Sertoli cell proliferation.
- DBP-exposed group exhibited higher serum FSH levels and lower testicular testosterone levels compared to controls.
Conclusions:
- In utero DBP exposure significantly increases Sertoli cell numbers and proliferation from postpuberty into adulthood.
- This phthalate exposure leads to a persistent decrease in testicular testosterone levels.
- Elevated serum FSH levels in DBP-exposed rats suggest a disruption in the hypothalamic-pituitary-gonadal axis.
Abstract:
Pregnant Sprague-Dawley rats were orally administered di( n-butyl)phthalate (DBP; 100 mg/kg/day) on gestation days (GD) 12 to 21. We investigated the male offspring and probed morphological alterations in Sertoli cells at 7, 9, 14, and 17 weeks of age. Parameters assessed in this study included offspring number, sex ratios, body weights, testis weights, seminiferous tubule (ST) profile numbers and diameters, number of vimentin-labeled Sertoli cells, and both testosterone and follicle-stimulating hormone (FSH) levels. Testicular weight/body weight ratios and the numbers and diameters of ST in maximum transverse testicular sections were statistically similar at weeks 7 and 9; however, at weeks 14 and 17, they were statistically different and displayed higher BrdU-positive Sertoli cells/Sertoli cell ratios in the DBP treatment group. Noteworthily, the serum FSH levels were higher and testicular testosterone levels were lower in the DBP treatment group. To our knowledge, the present study is the first to report that in utero DBP exposure significantly increased Sertoli cell numbers and their cellular proliferation from postpuberty to adulthood, with a significant decrease in testicular testosterone and an increase in FSH.
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