Decreased Capacity for Sperm Production Induced by Perinatal Bisphenol A Exposure Is Associated with an Increased Inflammatory Response in the Offspring of C57BL/6 Male Mice

Abstract

Many previous studies have indicated the adverse effects of bisphenol A (BPA) on sperm production and quality; however, the mechanisms underlying BPA male reproductive toxicity have yet to be elucidated. The main purpose of this study was to investigate the effect of perinatal exposure to BPA on the spermatogenic capacity of male offspring, and to explore the possible influence of inflammatory responses in BPA reproductive toxicity. Twenty-one pregnant C57BL/6mice were randomly divided into three groups: a control group, a group receiving 0.2 μg/mL (LBPA), and a group receiving 2 μg/mL of BPA (HBPA), all via drinking water from gestational day 6 to the end of lactation. After weaning, one male mouse was randomly selected from each group (n = 7/group); these three mice were fed a normal diet and drinking water for 1 month. Levels of serum testosterone (T) and tumor necrosis factor (TNF)-α were then measured in all mice. Sperm count and the proportion of sperm malformation were also determined. The levels of Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, and aryl hydrocarbon receptor (AhR) protein expression in the testis tissue were determined. Analysis showed that the proportion of sperm malformation increased in the LBPA and HBPA groups (p < 0.05). Sperm count significantly decreased only in the HBPA group (p < 0.05), while the levels of serum TNF-α increased in the LBPA and HBPA groups (p < 0.05). Levels of serum T decreased significantly in the HBPA group, compared with controls (p < 0.05). Levels of TLR4 and NF-κB protein expression in the testis were significantly higher in the LBPA and HBPA groups (p < 0.05 or p < 0.01), while AhR protein expression was higher and seminiferous tubules in the testis showed more damage in the HBPA group compared to controls (p < 0.05 and p < 0.01, respectively). Our results showed that perinatal exposure to low or high doses of BPA decreased the capacity for spermatogenesis in male offspring, which may be associated with an inflammatory response activated by the TLR4/ NF-κB and AhR signaling pathways in the testis.

Aryl Hydrocarbon Receptor as a Target for Lycopene Preventing DEHP-Induced Spermatogenic Disorders

“…Our data suggested that LYC is beneficial for decreasing of the levels of nuclear damage to DNA and deformity rate and increasing the values of sperm motility, number, and density induced by DEHP. A study showed that the decreasing capacity of spermatogenesis in male offspring might be associated with the AHR signaling pathways in the testes . It has been reported that AHR overexpression was found in Sertoli, Leydig, and spermatid cells of infertile subjects .…”

Mechanisms of Testicular Disruption from Exposure to Bisphenol A and Phtalates

“…Notably, during lactation, prolonged exposure to water contaminated with 0.2 or 2 µg/mL of BPA was not associated with any changes in epididymal or testicular volume compared with the control group. However, the male offspring of dams exposed to 2 µg/mL BPA showed reduced testosterone and sperm concentration and an increase in abnormal cells compared with controls [61]. Another interesting result from this study was the finding of a change in the inflammatory pathways in the groups exposed to the highest dose of BPA (increase in TNFα and higher NFkB and TLR4 protein expression).…”

Investigation of Chemical Composition and Fiber-Occurrence in Inhalable Particulate Matter Obtained from Dry Cutting Processes of Carbon Fiber Reinforced Concrete Composite, Concrete and the Carbon Fiber Reinforcement Materials

“…Furthermore, the BPA concentration in PM 2.5 of the C 3 is slightly higher than that in the PM 10 fraction with 24.9 µg/mg. In animal studies, doses in the low µg/kg body weight (BW) range already showed significant effects on the reproduction system and allergic asthmatic responses (Meng et al 2018;Yanagisawa et al 2019). Exposure rates per cm 3 cut material can be calculated according to the formula with ER = exposure rate in µg/(min × kg BW × cm 3 cut material), BW = body weight in kg, BPA conc.…”