Altered reproductive success in rat pairs after environmental-like exposure to xenoestrogen

Abstract

Endocrine-disrupting compounds (EDCs) have the capacity of altering the normal function of the endocrine system. EDCs have shown dramatic effects on the reproductive biology of aquatic wildlife and may affect human reproduction as well. Studies on EDCs in mammalian species have often investigated the effects of short-term, high doses on male and female reproductive physiology. However, it is difficult to predict from such studies the effects of EDC on populations that are exposed to very low doses throughout their life via contaminated food and water. We studied the effects of EDC on mammalian reproduction with an environmental-like protocol where the endpoint is the reproductive success of exposed pairs. We focused on a subclass of EDC, the xenoestrogens, which mimic the action of natural oestrogen hormones. Male and female rats were exposed to low doses of the pure oestrogen, ethynyloestradiol, during development, by oral administration to their mothers during pregnancy and lactation, and to them until puberty. We evaluated the effects of the exposure on development and reproductive physiology of individuals, and on fertility and fecundity of pairs in which both members had been exposed to the same treatment. We found that low doses caused major reproductive deficits in the experimental animals. Very low, environmentally relevant doses did not have evident effects on exposed animals; however, the fecundity of exposed pairs was substantially altered. Environmentally relevant doses of xenoestrogens which have no evident physiological effects can alter the reproductive success of exposed pairs in natural populations.

Figure 1

Oestrous cycles of female rats exposed to 4 ng kg⁻¹d⁻¹ (EE4) or 400 ng kg⁻¹d⁻¹ (EE400) EE during development. (a) Oestrous cycle type as determined by observation of a 15-day series of vaginal smears. Cycle was scored as irregular when there was no alternation of dioestrus, pro-oestrus and oestrous with a 4- to 5-day period. Most EE400 females showed irregular oestrous cycle with an abnormal vaginal cytology typical of persistent oestrous of aged and perinatally oestrogen-treated females. Pearson Χ², p<0.0001. (b) The mean oestrous score was higher (4=oestrous) in EE400 females than in the other two groups. Hash, p<0.01, Kruskal–Wallis ANOVA followed by Dunn's post hoc test, EE400 versus OIL and EE4.

Figure 2

Fertility of pairs of rats which had been exposed during development to 4 ng kg⁻¹d⁻¹ (EE4) or 400 ng kg⁻¹d⁻¹ (EE400) of EE. No EE400 female gave birth to life pups. There was no difference in fertility between OIL and EE4 females. Asterisk, p<0.001, Pearson Χ².

Figure 3

Pairs of rats that were exposed to 4 ng kg⁻¹d⁻¹ of EE (EE4) during development generated more live pups, and particularly more male pups, than control treated pairs. Asterisk, p<0.02, t-test.

Figure 4

Pairs of rats that were exposed to 4 ng kg⁻¹d⁻¹ of EE (EE4) during development generated pups with the same average body mass as control treated animals. Owing to the higher number of pups per litter (figure 3), however, EE4 pairs had heavier litters. Asterisk, p<0.03, t-test.