Effect of superovulation on the expression of tissue inhibitor of metalloproteinases-3 (TIMP-3) in murine endometrium

Abstract

Objective: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in 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 murine endometrium during this period is TIMP-3. This study was performed to evaluate the expression of TIMP-3 mRNA during periimplantation period in the hyperstimulated murine endometrum.Design: Laboratory research.Materials/Methods: Quantitative, competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR) was performed to evaluate the expression of TIMP-3 mRNA during periimplantation period in the hyperstimulated murine endometrum from pregnant uteri of gestation day (g.d.) 6.0 and 7.0 after injection of pregnant mare serum gonadotropin (PMSG) 5 IU and 10 IU. TIMP-3 mRNA expression was corrected by the simultaneous transcript level of matrix metalloproteinases-9 (MMP-9) which is mainly expressed by mouse embryos, since TIMP-3 is expressed mainly in the murine endometrium adjacent to implanting mouse embryos.Results: In both PMSG 5 IU and 10 IU groups, the expression of TIMP-3 mRNA showed an increase while MMP did not show a significant difference compared to control group (natural coitus without PMSG injection), on g.d. 6.0 and 7.0. Corrected TIMP-3 mRNA expression for MMP-9 also showed a high level of transcription in murine endometrium in the superovulation groups.Conclusions: This study suggests that ovarian hyperstimulation by gonadotropin, which produces many oocytes and embryos, may have a detrimental effect on embryonic implantation via its relevant endometrial remodeling process by the increase in expression of TIMP-3 in murine endometrium.Supported by: None. Objective: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in 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 murine endometrium during this period is TIMP-3. This study was performed to evaluate the expression of TIMP-3 mRNA during periimplantation period in the hyperstimulated murine endometrum. Design: Laboratory research. Materials/Methods: Quantitative, competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR) was performed to evaluate the expression of TIMP-3 mRNA during periimplantation period in the hyperstimulated murine endometrum from pregnant uteri of gestation day (g.d.) 6.0 and 7.0 after injection of pregnant mare serum gonadotropin (PMSG) 5 IU and 10 IU. TIMP-3 mRNA expression was corrected by the simultaneous transcript level of matrix metalloproteinases-9 (MMP-9) which is mainly expressed by mouse embryos, since TIMP-3 is expressed mainly in the murine endometrium adjacent to implanting mouse embryos. Results: In both PMSG 5 IU and 10 IU groups, the expression of TIMP-3 mRNA showed an increase while MMP did not show a significant difference compared to control group (natural coitus without PMSG injection), on g.d. 6.0 and 7.0. Corrected TIMP-3 mRNA expression for MMP-9 also showed a high level of transcription in murine endometrium in the superovulation groups. Conclusions: This study suggests that ovarian hyperstimulation by gonadotropin, which produces many oocytes and embryos, may have a detrimental effect on embryonic implantation via its relevant endometrial remodeling process by the increase in expression of TIMP-3 in murine endometrium. Supported by: None.