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Published on: March 6, 2018
In Utero Exposure to Di-n-butyl Phthalate Causes Modulation in Neurotransmitter System of Wistar Rats: A
1Department of Biotechnology and Genetics, M S Ramaiah College of Arts, Science and Commerce, Bangalore, India.
Insights
Di-n-butyl phthalate (DBP) exposure during development disrupts neuroendocrine regulation and causes developmental issues. This endocrine disruptor impacted neuroendocrine systems and had antiandrogenic effects across three generations of rats.
Area of Science:
- Environmental toxicology
- Developmental neurobiology
- Endocrinology
Background:
- Di-n-butyl phthalate (DBP) is an endocrine-disrupting chemical.
- Prenatal and lactational exposure to DBP can disrupt neuroendocrine regulation.
- Teratological studies are crucial for assessing fetal developmental impacts.
Purpose of the Study:
- To investigate the long-term effects of in utero and lactational DBP exposure on neuroendocrine regulation.
- To evaluate the impact of DBP on developmental outcomes and neuroendocrine parameters across three generations (F1-F3).
- To assess the antiandrogenic effects of DBP exposure.
Main Methods:
- Rats were exposed to DBP (500 mg/kg BW/day) or vehicle (olive oil) from gestation day 6 to postnatal day 30.
- Thyroid profile, estradiol, testosterone, and neurotransmitter levels (dopamine, serotonin, cortisol) were measured in dams and pups.
- Assessments were conducted at gestational day 19 (GD-19) and in one-month-old pups across three generations.
Main Results:
- DBP exposure significantly decreased thyroid profile and estradiol levels in dams (F0-F2).
- Developmental outcomes included underdeveloped fetuses and increased resorptions in exposed rats.
- Pups exhibited altered neurotransmitter levels (increased dopamine and cortisol, decreased serotonin) and significantly decreased testosterone in the third generation.
Conclusions:
- In utero and lactational DBP exposure impairs the neuroendocrine system in developing rats.
- DBP exhibits antiandrogenic effects, particularly evident in the third generation.
- These findings highlight the transgenerational impact of DBP on neuroendocrine and developmental health.
Abstract:
Neuroendocrine regulation is disrupted by di-n-butyl phthalate (DBP) when exposure occurs during the critical periods of fetal development, which can lead to neurological disorders. To evaluate the toxic potential of DBP, it is necessary to conduct teratological studies, which could determine impacts on the development of the fetus. The present study was designed to understand the sequelae of neuroendocrine regulation in one-month-old pups when rats were exposed to DBP (F1-F3) in utero and during lactation. The rats received DBP (500 mg/kg BW/day) dissolved in olive oil through oral gavage from gestation day 6 to postnatal day 30, while the control group received the olive oil (vehicle) during the same timeline. Following the exposure, thyroid profile and estradiol, which were measured at GD-19, exhibited a significant decrease (P < 0.05) in dams (F0-F2). The exposure resulted in developmental outcomes, including underdeveloped fetuses, and a notable number of resorptions in experimental rats. The one-month-old pups were assessed for serum thyroid profile and testosterone and neurotransmitters in discrete brain regions, cerebral cortex, cerebellum, and hippocampus for up to three generations. The levels of dopamine and cortisol showed a significant increase (P < 0.05), but serotonin levels decreased when examined in distinct brain regions of the experimental group as compared to the control. DBP, which is considered an endocrine disruptor, had the most impact on the third generation in this study, leading to a significant decrease in testosterone levels. In summary, in utero exposure to DBP impaired the neuroendocrine system and had an antiandrogenic effect in the three successive generations.
