HOXA10 mRNA expression and promoter DNA methylation in female pig offspring after in utero estradiol-17β exposure

Abstract

Early exposure to environmental estrogens may exert lasting impacts on health. In rodents, homeobox A10 (HOXA10) was demonstrated to be a target of early endocrine disruption, as indicated by persistent changes in uterine HOXA10 expression and promoter DNA methylation in the offspring. This study aimed at analyzing long-term effects of estradiol-17β on porcine uterine HOXA10. Therefore, offspring were exposed in utero to low (0.05 and 10μg/kg body weight/day) and high (1000μg/kg body weight/day) doses, respectively. We, furthermore, investigated whether promoter DNA methylation was generally involved in regulating HOXA10 expression. Unexpectedly, the maternal estrogen exposure did not distinctly impact HOXA10 expression and promoter DNA methylation in either pre- or postpubertal offspring. Although differential HOXA10 expression was observed in endometrial tissue during the estrous cycle and the pre-implantation period, no concurrent substantial changes occurred regarding promoter DNA methylation. However, by comparing several tissues displaying larger differences in transcriptional abundance, HOXA10 expression correlated with promoter DNA methylation in prepubertal, but not postpubertal, gilts. Thus, promoter DNA methylation could affect gene expression in pigs, depending on their stage of development. Clearly, early estrogen exposure exerted other effects in pigs as known from studies in rodents. This may be due to endocrine differences as well as to species-specific peculiarities of tissue sensitivity to estradiol-17β during critical windows of development.