Abstract
Attenuation of calcitonin gene expression in pregnant rat uterus leads to a block in embryonic implantation
Zhu,Li-Ji; Bagchi,Milan K.; Bagchi,Indrani C.
Endocrinology 139(1): 330-339
Publication date: 1998
The peptide hormone calcitonin plays a key role in calcium homeostasis inmany tissues, such as bone and kidney. Our previous studiesrevealed that the expression of calcitonin is dramatically inducedin the glandular epithelium of rat uterus between days 3-5of pregnancy before the onset of blastocyst implantation onday 5. Calcitonin expression is switched off once implantationhas progressed to day 6. The coincidence in timing suggestedthat calcitonin may function as a regulatory signal in the uterusduring the early events leading to implantation. Here we reportthat the implantation stage-specific expression of calcitonincan be specifically attenuated by administering antisense oligodeoxynucleotides(ODNs) directed against exon IV of calcitonin messenger RNAinto the uterine horns on day 2 of gestation. The loss of calcitoninmessenger RNA and protein expression upon antisense ODN treatmentis accompanied by a severe impairment in implantation of embryos.Based on the observations that 1) treatment with two differentantisense ODNs possessing different base compositions producedsimilar phenotypes; and 2) treatment with the complementarysense ODNs did not affect either calcitonin expression or implantation,we conclude that the effects of antisense ODNs on calcitoninexpression and implantation are specific and functionally linked.Our study strengthens the hypothesis that a transient expressionof calcitonin in the preimplantation phase uterus is criticalfor blastocyst implantation.
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