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Experimental Genetics Group
Biol Reprod. 2005 Feb;72(2):266-75. He H1, McCartney DJ1, Wei Q2, Esadeg S1, Zhang J1, Foster RA3, Hayes MA3, Tayade C1, Van Leuven F4, Croy BA1,5. 1Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada. 2Labatts Brain Tumor Research Center, Hospital for Sick Children, Toronto, Ontario, Canada. 3Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada. 4Experimental Genetics Group, Department of Human Genetics, K.U.Leuven, Leuven, Belgium 5Corresponding author. Full-length cDNA for a mouse gene A2-macroglobulin induced by pregnancy (A2mp) was cloned from mesometrial decidua at Gestation Day 10. The 4622-base pair cDNA encodes a protein of 1473 AA with >70% sequence identity and all typical domains of other A2M-family members in humans and rodents, despite unique absence of hepatic expression. The bait region is most distinct and has the greatest sequence similarity with rat acute-phase A2m. Northern blotting, reverse transcription and real-time-PCR, and in situ hybridization studies using C57Bl/6 mice revealed uterine induction of A2mp during decidualization and strong, midgestational association with modifying spiral arteries. Ovaries, testes, lactating mammary glands, heart, and kidney were the only additional organs with A2mp expression that was localized to granulosa and cumulus cells in secondary follicles; primary seminiferous epithelium, including Sertoli cells, mammary alveolar, and ductal epithelium; cardiac endothelium; and renal collecting tubules, respectively. Infusion of native human A2M into pregnant alymphoid or interferon-gamma gene-ablated mice overcame blocks to pregnancy-induced spiral artery modification in these strains. Activated human A2M was also effective, suggesting mechanisms independent of proteinase inhibition. Identification of cytokines, growth factors, or other molecules bound to A2MP should provide new insights into decidualization, spiral artery modification, and cardiovascular adaptation to pregnancy.  FULL TEXT |
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