Effect of prenatal exposure to lead on estrogen action in the prepubertal rat uterus

Abstract

Lead is a widely spread environmental pollutant known to affect both male and female reproductive systems in humans and experimental animals and causes infertility and other adverse effects. The present paper investigated the effects of prenatal exposure to lead on different parameters of estrogen stimulation in the uterus of the prepubertal rat. In prenatally and perinatally exposed rats, estrogen-induced endometrial eosinophilia, endometrial stroma edema, and eosinophil migration towards the endometrium, and uterine luminal epithelial hypertrophy are enhanced while several other responses to estrogen appear unchanged. These effects may contribute to decrease in fertility following prenatal exposure to lead. The striking difference between most of these effects of prenatal exposure and the previously reported effects of chronic exposure to lead suggests that prenatal exposure to lead may neutralize the effects of chronic exposure to lead, providing partial protection of cell function against the adverse effects of chronic exposure to lead. We propose that the mechanism involved, named imprinting or cell programming, persisted through evolution as a nongenetic adaptive mechanism to provide protection against long-term environmental variations that otherwise may cause the extinction of species not displaying this kind of adaptation.

Figure 1

Comparison of the effects of prenatal exposure to lead and chronic exposure to lead on estrogen-induced uterine eosinophilia measured in the endometrium. Prenatally exposed rats were subjected to s.c. injection of their pregnant mothers with a lead acetate (P) or saline physiological solution at their 14th day of pregnancy. From birth on, the pups were breastfed by their mothers. At the age of 21 days the animals were treated with estradiol-17β (E) or vehicle (V). The uteri were obtained 6 h after hormone or vehicle administration. Previously reported data from chronically exposed rats are shown for comparison purposes (see [14]). Bars indicate means (expressed as percentage of maximal response to estradiol) ± standard error of the mean. Statistics: LSD test. ** or ⁺⁺, P < 0.01; *** or ⁺⁺⁺, P < 0.001; *, comparisons to the homologous condition without estrogen; ⁺, comparisons to the homologous condition without lead.

Figure 2

Comparison of the effects of prenatal exposure to lead and chronic exposure to lead on estrogen-induced edema in deep endometrial stroma, measured as increases in reciprocal value of cell density. Prenatally exposed rats were subjected to s.c. injection of their pregnant mothers with a lead acetate (P) or saline physiological solution at their 14th day of pregnancy. From birth on, the pups were breastfed by their mothers. At the age of 21 days the animals were treated with estradiol-17β (E) or vehicle (V). The uteri were obtained 6 h after hormone or vehicle administration. Previously reported data from chronically exposed rats are shown for comparison purposes (see [14]). Bars indicate means (expressed as percentage of maximal response to estradiol) ± standard error of the mean. Statistics: LSD test. *, P < 0.05; **, P < 0.01; *** or ⁺⁺⁺, P < 0.001; *, comparisons to the homologous condition without estrogen; ⁺, comparisons to the homologous condition without lead.

Figure 3

Comparison of the effects of prenatal exposure to lead and chronic exposure to lead on estrogen-induced hypertrophy of luminal epithelial cells, measured as increase in their cellular volume. Prenatally exposed rats were subjected to s.c. injection of their pregnant mothers with a lead acetate (P) or saline physiological solution at their 14th day of pregnancy. From birth on, the pups were breastfed by their mothers. At the age of 21 days the animals were treated with estradiol-17β (E) or vehicle (V). The uteri were obtained 24 h after hormone or vehicle administration. Previously reported data from chronically exposed rats are shown for comparison purposes (see [14]). Bars indicate means (expressed as percentage of maximal response to estradiol) ± standard error of the mean. Statistics: LSD test. **, P < 0.01; *** or ⁺⁺⁺, P < 0.001; *, comparisons to the homologous condition without estrogen; ⁺, comparisons to the homologous condition without lead.

Figure 4

Comparison of the effects of prenatal exposure to lead and chronic exposure to lead on estrogen-induced myometrial hypertrophy, measured as increase in cell volume of circular myometrium. Prenatally exposed rats were subjected to s.c. injection of their pregnant mothers with a lead acetate (P) or saline physiological solution at their 14th day of pregnancy. From birth on, the pups were breastfed by their mothers. At the age of 21 days the animals were treated with estradiol-17β (E) or vehicle (V). The uteri were obtained 24 h after hormone or vehicle administration. Previously reported data from chronically exposed rats are shown for comparison purposes (see [14]). Bars indicate means (expressed as percentage of maximal response to estradiol) ± standard error of the mean. Statistics: LSD test. **, P < 0.01; ***P < 0.001; *, comparisons to the homologous condition without estrogen.