Effect of superovulation on the expression of tissue inhibitor of metalloproteinase-3 in the murine endometrium

Abstract

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in the endometrial remodeling process during embryonic trophoblast invasion. Previous studies, using in situ hybridization, revealed that the predominant proteinase expressed by the implanting mouse embryo is matrix metalloproteinase-9 (MMP-9), and the major tissue inhibitor of metalloproteinases (TIMP) produced in the murine endometrium during this period is TIMP-3. Quantitative, competitive-reverse transcription-PCR was performed to evaluate the expression of TIMP-3 mRNA during the implantation period in the hyperstimulated murine endometrium from pregnant uteri of gestation day (g.d.) 6.0 and 7.0 after injection of 5 and 10 IU pregnant mare serum gonadotropin (PMSG). In PMSG groups, the expression of TIMP-3 mRNA, normalized by MMP-9 mRNA, showed a significant increase compared to the control group (natural coitus without PMSG injection) on g.d. 6.0 (p = 0.039) and an increasing tendency on g.d. 7.0. This study suggests that ovarian hyperstimulation by gonadotropin may have a detrimental effect on embryonic implantation possibly via an altered endometrial remodeling process by the increase in expression of TIMP-3 in the murine endometrium.