Connecting with Mom -Trophoblast and Placenta
Session: Poster Session C
Jayasri Basu, PhD
Director, Graduate Medical Education, Dept. OB/GYN
BRONXCARE HEALTH SYSTEM
Bronx, New York, United States
In normal pregnancy, the extravillous trophoblasts traverse through the decidua to reach the uterine spiral arteries, and transform the high-resistant small diameter uterine spiral arteries into high-capacity low resistant blood vessels. Trophoblast invasion and remodeling of the uterine spiral arteries are dependent on the activity of placental Matrix Metalloproteinase-9 (MMP-9) protein; which in turn is regulated by the placental protein Tissue Inhibitor of Metalloproteinase-1 (TIMP1). Dysregulation and imbalance between the activity of proteases and protease inhibitors have been implicated in the pathophysiology and progression of several diseases. We hypothesize that in preeclampsia, an imbalance between MMP-9 and TIMP1 proteins occurs. The expression patterns and the ratios of these two placental proteins were therefore compared between normal pregnancies and preeclampsia, to determine whether dysregulation between MMP-9 and TIMP1 proteins could have a role in preeclampsia. For the study, p<span style="mso-bidi-font-family: Tahoma; color: black;">lacentas were collected from women with uncomplicated pregnancies and from women with preeclampsia, as diagnosed by ACOG's criteria; with gestational age of both groups being 37 to 40 weeks. Chorionic villi were isolated from each placenta. The two proteins were analyzed using ELISA kits that used monoclonal antibody as capture antibody to either human MMP-9 or TIMP1 protein (R&D Systems). Independent t Test and Spearman's correlation were carried out that considered p< 0.05 as significant. The results depict that a total of 93 placentas were collected, 54 from normotensive women and 39 from women with preeclampsia. Data are reported as mean + S.D. Placental weights were comparable between normal pregnancies and preeclampsia (456 + 98 grams vs 430 +148 grams, respectively). Similarly age was comparable between the two groups (28 + 6 years vs 26 + 6 years in controls and preeclampsia, respectively). Placental MMP-9 protein was significantly higher in preeclampsia (31.05 + 15.73 vs 22.29 +10.87 ng/100 mg tissue; p< 0.003), while TIMP1 protein was significantly lower (19.64 + 28.92 vs 34.95 + 27.45 ng/100 mg tissue; p< 0.000). The ratio of MMP-9/TIMP1 was significantly higher in preeclampsia (p < 0.000) (1.55 + 2.70 vs 10.16 + 14.96 in controls and preeclampsia, respectively). No correlation was observed between the two placental proteins, nor the proteins with any of the studied variables. To conclude, the finding of comparable placental weights between normotensive pregnancies and preeclampsia suggests that angiogenesis continues in preeclampsia even though the spiral arteries are not fully modified. The significantly higher level of placental MMP-9 protein seen in preeclampsia, we suggest, could be a compensatory mechanism to breakdown the extracellular matrix, to enable the capillary plexus to grow; so that greater volume of blood could be delivered to the fetus in keeping with the fetal demand of the third trimester. The simultaneous analysis of placental TIMP1 protein expression in the same tissue was significantly low; that resulted in significantly higher MMP-9/TIMP1 ratio in preeclampsia. Preeclampsia is well known as a multifactorial disease. This dysregulation in placental MMP-9 and its cognate inhibitor TIMP1 protein allows the vascular dysfunction in preeclampsia to persist; and we suggest could be an additional contributory factor in the pathogenesis of preeclampsia.