Objective: To investigate the role of KiSS-1 and matrix metalloproteinase (MMP) 9 in trophoblasts in the pathogenesis of preeclampsia and their relation to perinatal outcome of neonates.
Methods: RT-PCR and western blot analyses were used to detect the MMP-9 and KiSS-1 expression levels in trophoblast of 40 patients with preeclampsia (15 cases of mild and 25 cases of severe preeclampsia) (preeclampsia group) and 20 cases of term pregnancy (normal pregnancy group) and their correlations with symptoms and perinatal outcome of neonates were analyzed.
Results: (1) The KiSS-1mRNA and metastin expression levels in trophoblasts of preeclampsia group were 1.73 +/- 0.24 (A value) and (78.4 +/- 8.0) microg/100 microg total protein separately, those of mild preeclampsia were (1.50 +/- 0.15) and (72.4 +/- 6.9) microg/100 microg total protein, and severe preeclampsia were (1.87 +/- 0.20) and (83.52 +/- 3.57) microg/100 microg total protein, which were all significantly higher than those of normal pregnancy group [1.24 +/- 0.25, P < 0.01, and (63.4 +/- 2.7) microg/100 microg total protein, P < 0.01], especially those in severe preeclampsia. (2) The MMP-9 mRNA and MMP-9 expression levels in trophoblasts of preeclampsia group were 0.09 +/- 0.06 and (9.6 +/- 4.2) microg/100 microg total protein, those of mild preeclampsia were 0.11 +/- 0.08 and (10.0 +/- 3.2) microg/100 microg total protein, and severe preeclampsia were 0.07 +/- 0.05 and (7.8 +/- 2.0) microg/100 microg total protein, which were all significantly lower than those of normal pregnancy group [0.17 +/- 0.10, P < 0.01, and (17.9 +/- 7.3) microg/100 microg total protein, P < 0.01]. (3) The expression level of KiSS-1mRNA and metastin in preeclampsia group were positively correlated with MAP, urinary protein per 24 hours, the correlation coefficients between KiSS-1mRNA and MAP, urinary protein per 24 hours were 0.610 (P = 0.023), 0.397 (P = 0.003), and between metastin and MAP, urinary protein per 24 hours were 0.713 (P = 0.011), 0.638 (P = 0.002), separately. The expression level of KiSS-1mRNA and metastin in preeclampsia group was significantly positively correlated with the occurrence of fundus oculi artery spasm, correlation coefficients were 0.499 (P = 0.000) and 0.511 (P = 0.000). The MMP-9mRNA and MMP-9 expression levels were negatively correlated with MAP, urinary protein per 24 hours and the occurrence of fundus oculi artery spasm, correlation coefficients between MMP-9mRNA and MAP, urinary protein per 24 hours, the occurrence of fundus oculi artery spasm were 0.561 (P = 0.042), 0.275 (P = 0.039), 0.346 (P = 0.001), between MMP-9 and MAP, urinary protein per 24 hours, the occurrence of fundus oculi artery spasm were 0.571 (P = 0.022), 0.375 (P = 0.048), 0.543 (P = 0.000), separately. (4) The expression level of MMP-9 mRNA and MMP-9 of preeclampsia was positively correlated with neonatal birth weight significantly, Pearson correlation coefficient was 0.651 (P = 0.000) and 0.544 (P = 0.004) separately, while the expression levels of KiSS-1mRNA and KiSS-1 of preeclampsia were negatively correlated with neonatal birth weight significantly, Pearson correlation coefficients were 0.759 (P = 0.000) and 0.865 (P = 0.000) separately. (5) The expression level of MMP-9 showed decreased tendency with the severity of newborn asphyxia, while the expression level of KiSS-1 showed increased tendency (P < 0.05).
Conclusion: The expression imbalance of MMP-9 and KiSS-1 in trophoblasts may play an important role in the pathogenesis of preeclampsia, and correlate to perinatal outcome of neonates.