SRA

The uterine cervix is the boundary structure between the uterus and the vagina and is a key component of the female reproductive tract for the maintenance of pregnancy and timing of parturition. Here we report on a comparative transcriptomic study of the cervix of four placental mammal species, mouse, guinea pig, rabbit and the basal eutherian mammal, armadillo, Dasypus novemcinctus, and one marsupial species, Monodelphis domestica. Our aim is to investigate the evolution of cervical gene expression as related to putative mechanisms for functional progesterone withdrawal. Our main findings are: 1) The patterns of gene expression found in eutherian species is consistent with the notion that an increase in the ratio of E/P4 signaling strength is critical for cervical remodeling. How the increased E/P4 ratio is achieved, however, is variable between eutherian species. 2) None of the genes related to steroid signaling modulated in eutherian species change expression during opossum gestation, suggesting that the role of P4 signaling in cervical remodeling evolved after the common ancestor of marsupials and placental mammals. 3) A tendency for decreased expression of progesterone receptor co-activators (NCOA1, -2 and -3, and CREBP) towards term is a shared derived feature of eutherians. This finding suggests that parturition is associated with broad scale histone de-acetylation. We tested this hypothesis by performing Western-blotting on mouse cervix and found evidence for a striking degree of histone de-acetylation in labor. This finding may have important implications for the control of premature cervical remodeling and preterm birth in humans. Overall design: We sequenced mRNA from cervix samples at different stages of pregnancy of four placental mammal species (one previously uploaded) and one marsupial species.