Interaction of bisphenol A (BPA) and soy phytoestrogens on sexually dimorphic sociosexual behaviors in male and female rats

Abstract

Concerns have been raised regarding the potential for endocrine disrupting compounds (EDCs) to alter brain development and behavior. Developmental exposure to bisphenol A (BPA), a ubiquitous EDC, has been linked to altered sociosexual and mood-related behaviors in various animal models and children but effects are inconsistent across laboratories and animal models creating confusion about potential risk in humans. Exposure to endocrine active diets, such as soy, which is rich in phytoestrogens, may contribute to this variability. Here, we tested the individual and combined effects of low dose oral BPA and soy diet or the individual isoflavone genistein (GEN; administered as the aglycone genistin (GIN)) on rat sociosexual behaviors with the hypothesis that soy would obfuscate any BPA-related effects. Social and activity levels were unchanged by developmental exposure to BPA but soy diet had sex specific effects including suppressed novelty preference, and open field exploration in females. The data presented here reinforce that environmental factors, including anthropogenic chemical exposure and hormone active diets, can shape complex behaviors and even reverse expected sex differences.

Sex Specific Placental Accumulation and Behavioral Effects of Developmental Firemaster 550 Exposure in Wistar Rats

“…Animals were assessed for general activity and anxiety-related behavior as juveniles or as adults (no animals were tested at both ages) using standard procedures (see Supplemental Materials for more detail). For all tests except the running wheel, animals were transported down a short hallway to a nearby testing room on a covered rolling cart and tested after a short acclimation period, as we have done previously 26 , 33 , 39 . Testing was conducted within the first 4 hours of the dark cycle, recorded, and subsequently analyzed by TopScan software (Clever Sys Inc., Reston, VA) by observers blinded to exposure group.…”

“…Juvenile testing spanned PNDs 24–28 to ensure females would be tested prior to vaginal opening (pubertal onset) 26 . The same juvenile rats, one per sex per litter, were tested in two apparatuses: light/dark box (L/D; control: 10♀, 7♂, low: 7♀, 8♂, mid: 9♀, 8♂, high: 9♀, 6♂) and open field (OF; control: 8♀, 7♂, low: 7♀, 7♂, mid: 7♀, 6♂, high: 7♀, 5♂) using well-established methods as previously described by us and others 33 , 39 . Two main endpoints were used to assess anxiety-like behavior in the L/D box: latency to enter the light side and the number of entries made into the light side within the 10 minute testing period.…”

“…Video scoring was validated by hand by a second blinded observer using the program Stopwatch (courtesy of David A. Brown, Center for Behavioral Neuroscience, Emory University) as described previously 39 . Potential litter effects were controlled for in the statistical analysis (described below).…”

Endocrine disruption of gene expression and microRNA profiles in hippocampus and hypothalamus of California mice: Association of gene expression changes with behavioural outcomes

“…Other studies suggest that early exposure to GEN or phyto‐oestrogens in general can affect later social behaviours. A study with male and female rats found that, although BPA did not affect social and activity levels, GEN in a soy‐enriched diet suppressed novelty preference and open field exploration in females at postnatal days 24‐28 82 . Perinatal exposure of male mice to GEN led to significant changes in anxiety and aggressive behaviours 83 .…”

Effects of Phytoestrogens on the Developing Brain, Gut Microbiota, and Risk for Neurobehavioral Disorders

“…These males had reduced number of positively stained cells in the amygdala neuronal cells staining positive for nitric-oxide synthase. A similar GEN exposure dose and period to Wistar rats resulted in sex-specific offspring effects with females displaying reduced novelty preference and exploration in an open field maze (41). On the other hand, developmental exposure to GEN (soy based diet, Purina 5001) from gestation through puberty has been suggested to abolish bisphenol A (BPA)-induced effects on anxiogenic behaviors in juvenile Wistar rats and restore normal sex differences in exploratory behavior in these animals (42).…”