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Abstract
The neural circuitry processing male sexual behavior is tightly regulated by testosterone and its neural metabolite estradiol. The present study evaluated the effects of adult exposure to low doses of nonylphenol (NP), a widespread environmental contaminant, on the neuroendocrine regulation of testosterone and expression of sexual behavior. Oral exposure of C57BL/6J males to NP (0.5, 5 or 50 μg/kg/day) for 4 weeks did not affect circulating levels of testosterone or the kisspeptin system, a key regulator of the gonadotropic axis. In contrast, mice exposed to NP at 5 μg/kg/day emitted an increased number and duration of ultrasonic vocalizations, took longer to reach ejaculation and showed increased number of mounts, intromissions and thrusts. This was associated with normal olfactory preference and locomotor activity, and increased anxiety level. Analysis of the neural circuitry that underlies sexual behavior showed changes in the number of cells expressing androgen and estrogen receptors in males exposed to NP at 5 μg/kg/day. The neural circuitry underlying sexual behavior is thus highly sensitive to adult exposure to NP. Furthermore, almost all the observed effects were induced at 5 μg/kg/day of NP, indicating that this endocrine disrupter triggers a non-monotonic response in the adult male mouse brain.
Highlights
Nonylphenol (NP) is an organic compound used in the manufacture of NP ethoxylate surfactants, but derives from alkylphenol degradation that occurs during sewing water treatment or in the environment
We investigated whether adult male mouse exposure to low doses of NP induces changes in the integrity of the HPG axis
The present study shows for the first time that chronic exposure of adult male mice to low doses of NP alters the expression of sexual behavior and increases anxiety-state level, without affecting the integrity of the HPG axis or testosterone levels
Summary
Nonylphenol (NP) is an organic compound used in the manufacture of NP ethoxylate surfactants, but derives from alkylphenol degradation that occurs during sewing water treatment or in the environment. Alkylphenols are nonionic surfactants that have been used since 1950 in a wide variety of industrial, agricultural and domestic applications such as soap, cosmetics, paints, herbicides and pesticides, or plastic fabrication. This results in major environmental contamination by NP of ecosystems including sewing water and rivers. Testosterone organizes perinatally and activates during adulthood the neural circuitry involved in the expression of sexual behavior. This complex behavior comprises pre-copulatory and copulatory phases. Exposure of adult rats to NP doses between 100 μg/kg/d and 300 mg/kg/d was found to reduce testosterone production[15,16,17,18] and increase LH levels[15], pointing out a vulnerability of this axis to high NP doses
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