Increased expression and localization of a serine protease inhibitor, protease nexin-1 (PN-1), in the ovary and uterus during implantation in rat

Protease nexin-1 (PN-1) is a serine protease inhibitor (serpin) that inacti vates several proteases, including thrombin, urokinase, plasminogen activat ors (PA), and plasmin. It also plays a role in regulating proteolytic activ ity generated by PA system. PN-1 is known to be involved in tissue remodeli ng, cellular invasiveness, matrix degradation, and tumor growth. However, t he role of PN-1 in female reproductive tracts, such as the uterus, ovary, a nd oviduct, during pregnancy is not known. The present study was designed t o investigate the changes of PN-1 mRNA level and localization in the tracts during implantation and early pregnancy by using reverse transcription (RT )-polymerase chain reaction (PCR) and in situ hybridization. We found that PN-1 mRNA levels were coordinately regulated during early pregnancy in a st age- and tissue-specific manner, such that an increased expression of PN-1 gene appeared at the time of the implantation period in the uterus and ovar y. Both the uterus and ovary synthesized PN-1 mRNA and their maximal PN-1 e xpression occurred on Day 6.5 postcoitum (p.c.). On 13.5 days of pregnancy, PN-1 level was low in the uterus and ovary. On the other hand, PN-1 mRNA i n the oviduct did not show after 6.5 days of pregnancy. It appears that PN- 1 mRNA in the uterus and ovary was highly regulated during early pregnancy, which might have an important role in implantation of rat blastocysts. PN- 1 was localized in endometrial stromal cells of the uterus and in granulosa cells of the unstimulated primary follicles in the ovary during periimplan tation period. Also, PN-1 mRNA expression was higher at implantation period than that at nonimplantation period of pregnancy. In conclusion, PN-1 is e xpressed in female reproductive tracts and highly regulated during implanta tion and early pregnancy. (C) 2001 Elsevier Science Ltd. All rights reserve d.