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Specific and Transient Up-Regulation of Proprotein Convertase 6 at the Site of Embryo Implantation and Identification of a Unique Transcript in Mouse Uterus During Early Pregnancy¹

^a Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia

The present investigation was conducted to identify and characterize an mRNA that was found by RNA differential display to be uniquely regulated at the sites of embryo implantation in mouse uterus. This mRNA was upregulated at the sites of blastocyst attachment at implantation and was identified as proprotein convertase 6 (PC6). PC6 mRNA level was low in the nonpregnant and early pregnant uterus before embryo implantation commenced (before Day 4.5, vaginal plug = Day 0). During the initiation and progression of blastocyst attachment (around Day 4.5), the mRNA was dramatically upregulated only at the implantation sites. The increased transcription was maintained on Day 5.5; the mRNA level declined slightly on Day 6.5 and then fell sharply to reach the nonpregnant level around Days 8.5–10.5. Thus, the upregulation is transient and coincides with the period of embryo attachment and implantation; it is also very specific to implantation sites. In situ hybridization analysis localized the mRNA expression predominantly in the decidual cells immediately surrounding the implanting embryo at the antimesometrial pole. Additionally, multiple mRNA species resulting from alternative splicing were observed in the uterus, as previously reported in the intestine and brain, and further analysis of these transcripts identified a uterine-specific PC6 mRNA. These data lead us to suggest that PC6 plays an important role in the processes of stromal cell decidualization and embryo implantation.

¹ This research was supported by the Rockefeller Foundation Contraceptive 21 Program, the Wellcome Trust (grant 52666), the NH&MRC of Australia (grants 971297 to L.A.S. and 983212 to J.K.F.), and the Rockefeller/World Health Organization Initiative on Implantation.

² Correspondence: Gui-Ying Nie, Prince Henry's Institute of Medical Research, PO Box 5152, 246 Clayton Rd., Clayton, Vic 3168, Australia. FAX: 61 3 9594 6125; guiying.nie{at}med.monash.edu.au

³ Current address: Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan