Dietary exposure to low doses of bisphenol A: Effects on reproduction and development in two generations of C57BL/6J mice

Abstract

The present study was conducted to examine the effects of low-dose exposure to bisphenol A on reproduction and development in two generations of mice. Pregnant female C57BL/6J mice (F0) were fed a diet containing low doses of bisphenol A (0, 0.33, 3.3, or 33 ppm) from gestational day 6 through postnatal day 22, and the weanlings (F1 and F2) from each F0 and F1 dam group, respectively, were also fed these same concentrations of bisphenol A ad libitum until sacrifice. There were no treatment-related changes in body weight, body weight gain, food consumption, gestation length, or the number of live births on postnatal day 1 in F0 dams between the control group and bisphenol A groups. Sex ratio and viability were similar in all F1 pups. No treatment-related changes were observed in body weight, food consumption, developmental parameters, anogenital distance, or weight of any of the organs (liver, kidney, heart, spleen, thymus, testis, ovary, or uterus) in F1 and F2 adults in either sex. The epididymis weight was slightly higher with 0.33 and 3.3 ppm in F1 males, but this slight increase was neither dose dependent nor seen across generations. There were no treatment-related effects of bisphenol A on cauda epididymal sperm count or sperm motility in F1 or F2 males. These findings indicate that dietary exposure to bisphenol A between 0.33 and 33 ppm does not adversely affect reproduction or development as assessed in two generations of mice.

Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence, 2007–2013

“…As shown in Supplemental Material, Table S5, several studies have reported that low-dose BPA did not alter gestation length in gestationally plus neonatally exposed mice (Cabaton et al 2011; Kobayashi et al 2010), adult-exposed mice (Tyl et al 2008), or gestationally plus neonatally exposed SD rats (Kobayashi et al 2012). Cabaton et al (2011) reported that low-dose BPA decreased the number of pregnancies and successful deliveries in gestationally exposed mice.…”

Extensive metabolism and route-dependent pharmacokinetics of bisphenol A (BPA) in neonatal mice following oral or subcutaneous administration

“…Extensive toxicology studies have established no-observedadverse-effect-levels (NOAELs) ranging from 5 to 50 mg/kg/day, further reinforcing the significance of first pass metabolism for mitigating BPA's potential risk (Ema et al, 2001;Tyl et al, 2002Tyl et al, , 2008Howdeshell et al, 2008;Ryan et al, 2010;Kobayashi et al, 2010Kobayashi et al, , 2012Stump et al, 2010). Delclos et al (2014) and Churchwell et al (2014) reported reproductive effects in rat pups after gavage dosing of dams from gestational day 6 and subsequent gavage dosing of pups from PND1 with 100 and 300 mg/kg/day BPA but not with dosages of 2.7 mg/kg/day or lower.…”

Early programing of uterine tissue by bisphenol A: Critical evaluation of evidence from animal exposure studies

“…However, these results may not be reliable, as estrus cycling is not yet consistent in mice at this age, and given the small number of individual mice studied (n=5 per group). This study, and three others [69–71], examine effects of BPA on uterine weights. Unfortunately, none of these studies [61,67–71] reported measures to control for effects of the estrus cycle on uterine weights, i.e.…”