Vulnerability of the Neural Circuitry Underlying Sexual Behavior to Chronic Adult Exposure to Oral Bisphenol A in Male Mice

Abstract

There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.

Neuroendocrine and behavioral effects of maternal exposure to oral bisphenol A in female mice

“…Second-pregnancy dams were administered, by oral gavage, sesame oil (vehicle group) or sesame oil containing BPA (Sigma-Aldrich) at 5 mg/kg body weight per day (BPA-NOAEL group) or BPA at 0.050 mg/kg body weight per day (BPA-TDI group). Treatments were carried out each day from gestational day 15 until postnatal day 21 (Picot et al 2014). After weaning, female offspring were allowed to grow until analyses.…”

Sexual Behavior: From Hormonal Regulation to Endocrine Disruption

“…Exposure to BPA for 2 weeks has no effect on male rats [66]. By contrast, longer periods of exposure of male mice to BPA increased the times to mounting, intromission and ejaculation, and decreased the numbers of intromissions and thrusts in both naïve and sexually experienced male mice [63]. Similar differences between short- and long-term exposures were observed for corncob bedding and derived tetrahydrofuran-diols [67, 68].…”

“…Decatanzaro et al [61] observed only a fewer number of intromissions in animals exposed to BPA in a high-phytoestrogen diet. In addition, male mice exposed to BPA displayed less lordosis behavior than the vehicle group when gonadectomized and primed with E2 and progesterone, indicating a greater masculinization of behavior [63]. When given a choice between control and BPA-exposed partners, female mice preferred controls over BPA-exposed males [65].…”

“…When given a choice between control and BPA-exposed partners, female mice preferred controls over BPA-exposed males [65]. BPA had no neuroanatomical effects on the number of calbindin-immunoreactive neurons in the preoptic area or kisspeptin cells in the AVPV [63]. …”

“…The other 9 studies found no effects on adult levels of testosterone, E2, and gonadotropins [42, 43, 48, 49, 52, 93, 94]. In mice, no change in hormone levels was observed following exposure to BPA or EE [61, 63, 99]. Exposure to methoxychlor did not change basal hormone levels but prevented the increase in testosterone levels following exposure to females [60].…”