IDENTIFICATION AND CELLULAR-LOCALIZATION OF UNIQUE INTERFERON MESSENGER-RNA FROM HUMAN PLACENTA

Although constitutive expression of trophoblast or pregnancy-associate d interferon (IFN) has long been recognized, their cDNA sequences have been determined for only ruminant ungulates. Here we show a human tro phoblast IFN (htIFN) cDNA whose nucleotide sequence is very similar (8 5% identity) to that of ovine and bovine trophoblast IFNs, IFN tau s. Like ruminant IFN tau s, htIFN cDNAs contain an open reading frame of 195 codons including a signal sequence of 23 amino acids, resulting in a mature polypeptide of 172 amino acids. The deduced amino acid seque nce of htIFN shares 73, 62, and 56% identities with ovine IFN tau, hum an IFN alpha II, and human IFN alpha I, respectively. However, the exp ression of htIFN is not limited to a specific period of pregnancy beca use transcripts of htIFN genes are detected in human lymphocytes, cell s obtained by amniocentesis (amniocytes), first trimester, and term pl acentas. Human trophoblast IFN mRNA is localized mainly in extravillou s trophoblast cells of placental villi, particularly in the migrating cytotrophoblast cells, which eventually replace maternal endothelial c ells in spiral arteries of the decidua. Both sense and antisense mRNAs for human IFN alpha II are localized in the outer layer of villous st ructures. Coexistence of these mRNAs at the placental villi throughout pregnancy suggests that, in addition to a role in placental cell grow th and differentiation, IFNs may play a role protecting the fetus in v iral environments.