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Prolonged treatment with estrogen causes the cervix of the ewe to redifferentiate to become more like uterus, and results in permanent infertility. Such permanent infertility has been observed only in ewes that have received two successive exposures to estrogen, raising the possibility that the initial exposure has a priming effect for subsequent treatment. In the study presented here, we examined whether any priming effects could be detected in the development of uterus-like histological changes in cervix of ewes given a single or two successive treatments with estradiol. Exposure to estradiol for 180 days resulted in stratified squamous hypertrophy of the cervical epithelium and also produced glandular hyperplasia, an increased proportion of lamina propria tissue in the endocervix, and fewer cervical folds. During the 30 days after treatment ceased, the epithelium returned to normal, while changes in cervical structure, as measured by reduced number of folds, became more marked. A second treatment with estradiol 180 days later produced a response similar to that after the first exposure, so it was not possible to identify any specific priming effect of the initial treatment with estrogen. However, treatment with estrogen established a process of cervical redifferentiation, and some aspects of this change appeared to be dependent on the withdrawal of estrogen.

Development of Uterus-Like Redifferentiation in the Cervix of the Ewe after Exposure to Estradiol-17β