Date Published: October 15, 2018
Publisher: Public Library of Science
Author(s): Ji-Jie Liu, Ce Guo, Bo Wang, Meng-Xing Shi, Yang Yang, Zhen Yu, Xiu-Hong Meng, De-Xiang Xu, Judith Homberg.
Although use of fenvalerate has increased dramatically over the past decade, little is known about their potential adverse effects on growth and development. The purpose of this study was to examine the effects of maternal fenvalerate exposure during pregnancy on growth and neurobehavioral development in the offspring. Pregnant mice were orally administered to fenvalerate (0.2, 2.0, and 20 mg/kg) daily throughout pregnancy. The tests of growth and neurobehavioral development were performed during lactation period. A series of neurobehavioral tasks were carried out from lactation to puberty. Anxiety-related behaviors were evaluated by open-field and elevated plus maze. Morris Water Maze was used to assess spatial learning and memory ability. Results showed that maternal fenvalerate exposure during pregnancy markedly delayed growth development of neonatal offspring during lactation. In addition, anxiety-like behaviors were increased in fenvalerate-exposed male offspring. Moreover, spatial learning and memory was severely impaired in female offspring. Taken together, maternal fenvalerate exposure during pregnancy delayed growth and neurobehavioral development in a gender-dependent manner. Additional study is required to explore the underlying mechanism through which maternal fenvalerate exposure during pregnancy induces impairment of growth and neurobehavioral development.
Fenvalerate, a widely used pyrethroid insecticide, has become a new major public health problem . Several epidemiological reports showed that fenvalerate and its metabolites were detected in bovine milk  and human samples, such as breast milk  and urine . An investigation found that maternal urinary metabolite levels were about 4–10 times higher than those of general population . More evidences suggest that it should be focus on the impairment induced by fenvalerate exposure. Previous studies have focused on neurotoxicity, reproductive toxicity of fenvalerate [6–8]. In addition, increasing evidence demonstrates that fenvalerate has endocrine disruptive effects . An early study showed that fenvalerate presented weak estrogen activities, strong anti-androgen effect and antagonistic effect on thyroid receptor (TR) signal . According to our laboratory’s earlier report, fenvalerate exposure during puberty interfered with the synthesis of testosterone and estradiol during the developing brain .
The ICR mice (8–10 weeks old; 32–34 g in male mice; 28–30 g in female mice) were purchased from Beijing Vital River whose primary colonies were all introduced from Charles River Laboratories, Inc. The mice were freely allowed to access to food (Beijing Keao Xieli Feed Co, LTD, Beijing 100107) and water at any time. One week prior to use, they were held in a room that was commanded lighting (12 h light/12 h dark cycle), temperature (20–25C) and humidity (50±5%). For mating purposes, four females and two males spend night together starting at 9:00 PM, and females were examined by 7:00 AM the next morning. If a vaginal plug appeared, gestational day (GD) 0 was established. This study was approved by the Association of Laboratory Animal Sciences and the Center for Laboratory Animal Sciences at Anhui Medical University (Permit Number: 13–0012). All procedures on animals followed the guidelines for humane treatment set by the Association of Laboratory Animal Sciences and the Center for Laboratory Animal Sciences at Anhui Medical University (Hefei, China).
Previous study from our laboratory showed that fenvalerate-exposure during puberty impaired spatial cognitive and behavioral development . The present study further found that maternal exposure to fenvalerate during pregnancy delayed growth and neurobehavioral development of mouse offspring in a gender-dependent manner. First, maternal exposure to fenvalerate markedly delayed growth of mouse offspring during lactation period. Second, we assessed neurobehavioral development from PND35 to PND50. We found that anxiety-related behaviors were increased in fenvalerate-treated male offspring. By contrast, spatial learning and memory was markedly impaired in female offspring, not in male offspring. As far as we know, this was the first study to evaluate the effects of maternal exposure to fenvalerate during pregnancy on growth and neurobehavioral development in mice offspring.