Parental exposure to benzo(a)pyrene in the peripubertal period impacts reproductive aspects of the F1 generation in rats
An experimental study using Wistar rats was conducted to test if peripubertal exposure to benzo(a)pyrene (BaP) in male rats consequently impaired the reproductive system of their male and female offspring.
A total of 40 males rats were randomly allocated into 4 even groups; 1) control, 2) 0.1μg/kg/day BaP, 3) 1μg/kg/day BaP and 4) 10μg/kg/day BaP, from post-natal day 23 to 53. For comparison, this is equivalent to the period of childhood (2 to 12 years old) and adolescence (12 to 16 years old) in humans. Once the rats reached adulthood (post natal day 90), the rats (F0 generation) were mated with non-treated females and their offspring (F1 generation) analysed.
Number of pups per liter was reduced to 8, with 4 male and 4 females, to equalise the individual outcomes. On post-natal day 1, 13 and 22, body weight and anogenital distance was measured on day 13, including the number of nipples. Age of testicular descent and preputial separation in male offspring was also recorded while similarly onset of puberty and first estrous cycle in female offspring was noted.
Further analysis of male and female offspring during puberty and sexual maturity included; testosterone, sperm count, morphology and histological analysis of the testis for male offspring, whilst estrous cycle, fertility and histological analysis of the ovaries was conducted in female offspring.
Initial results showed that both female and male offspring exposed to 0.1μg/kg/day and 1μg/kg/day of BaP, had a statistically significant reduction in weight, at post-natal day 1, 13 and 22. Anogenital distance in the male offspring was also significantly reduced, in both 0.1μg/kg/day and 1μg/kg/day BaP exposed groups, in contrast to the female offspring which showed no similar changes. However puberty onset, vaginal onset and first estrous age in the female offspring was significantly reduced in the 0.1μg/kg/day BaP exposed group. Interestingly, testicular descent was delayed in all the BaP exposed groups of male offspring.
Full analysis of body and organ weights on post-natal day 42 and 90, showed a continuing decrease in the body weight of females exposed to 0.1μg/kg/day BaP, while male offspring no longer showed any difference. Sperm analysis on post-natal day 90 showed impaired sperm production in all exposed groups, although this was most significant in the 1μg/kg/day BaP exposed group, with significantly reduced daily sperm production and number of mature spermatids. Histological analysis of the testis found a decrease in number of Leydig cells (1μg/kg and 10μg/kg), area of Leydig cell nuclei and volume of Leydig cell (all exposed groups) with a significant reduction in the percentage of normal tubules (0.1μg/kg and 1μg/kg).
Estrous cycle analysis of female offspring during adulthood showed a significant decrease in the number of estrous days (0.1μg/kg and 1μg/kg) and increase in diestrous days (0.1μg/kg). Fertility tests also showed a significant reduction in uterine + fetal weight, implantations and number of live fetuses (0.1μg/kg) while a dose dependent trend of ‘large fetus for pregnancy age’ was observed.
Histological analysis of the ovaries at post-natal day 90 showed a significantly altered ovarian structure, with significantly increased number of preantral and atretic follicles, and decrease in corpora lutea, for all exposed groups compared to control. Uterus histology also showed that both endometrium and uterine thickness was reduced by BaP exposure, although this was most significant in the 0.1μg/kg and 1μg/kg BaP group offspring.
Overall paternal peripubertal exposure to BaP negatively impacted the reproductive outcome in both male and female offspring demonstrating the toxicity of BaP and multigenerational effects.
SUMMARY: DOES EATING MEAT AFFECT FERTILITY
In this experimental rat study, benzo(a)pyrene, which is found particularly in grilled meat, negatively impacts the fertility of both male and female offspring, following exposure by the male father to low levels of benzo(a)pyrene (0.1μg/kg/day) during peripuberty.
- Reproductive system of rats is similar however not identical
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Zhan S, et al. (2015). Benzo(a)pyrene disrupts mouse preimplantation embryo development. https://doi.org/10.1016/j.fertnstert.2014.11.013
Xu G, et al. (2014). Early-life exposure to Benzo [a] pyrene increases mutant frequency in spermatogenic cells in adulthood. https://doi.org/10.1371/journal.pone.0087439
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Neal M S, et al. (2007). Follicle growth is inhibited by benzo-[a]-pyrene, at concentrations representative of human exposure, in an isolated rat follicle culture assay. https://doi.org/10.1093/humrep/del487
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