Elham Etesami1, Habib Nikukar2, Fariba Ramezanali3, Fahimeh Ghotbizadeh Vahdani4, Maryam Shahhoseini5, Raha Favaedi5, Azadeh Ghaheri6, Sara Seydabadi1, Mohammadreza Zamanian7. 1. Department of Stem Cell Biology, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 2. Department of Stem Cell Biology, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 3. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 4. Obstetrics and Gynecology Department, Imam Khomeini Medical Complex, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 6. Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 7. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Electronic address: mrzamanian@royaninstitute.org.
Abstract
OBJECTIVE: Nucleic acids released from the placenta into the mother's blood circulation system provide a valuable source of potential biomarkers for early detection of pregnancy complications such as preeclampsia (PE). PE affects nearly 5-10% of pregnancies worldwide and is a major contributor to the maternal and neonatal mortality and morbidity. It is known that altered placental expression of matrix metalloproteinases (MMPs) may cause shallow cytotrophoblastic invasion and ultimately lead to preeclampsia. The present study aimed to evaluate pattern of placental/fetal expression of the MMP family (MMP-2, MMP-9, MMP-14, MMP-15 and MMP-26) in preeclamptic women and compare it to normal pregnancies, using cell free fetal RNA (cff-RNA). METHODS: Blood samples were obtained from 20 pregnant women diagnosed with severe PE (28-32 weeks) and 40 control healthy pregnant women in two groups of either matched gestational age (N = 20) or 14 and 28 weeks pregnancies (each 10). cff-RNA was extracted from plasma, followed by reverse transcription of cff-RNA. Expression of MMP genes was measured using quantitative reverse transcription PCR (qRT-PCR). RESULTS: The expression levels of MMP-2, MMP-9 and MMP-15 were significantly increased, while MMP-14 expression level was significantly reduced and the expression of MMP-26 showed a relative increase in PE pregnancies compared to the control group. Additionally, increased level of MMPs expression was observed by comparing 14 and 28 weeks gestation age in normal pregnancy. CONCLUSION: Using cff-RNA, circulatory expression level of MMP-2, MMP-9, MMP-14 and MMP-15 were significantly altered in preeclampsia compared to normal pregnancies.
OBJECTIVE: Nucleic acids released from the placenta into the mother's blood circulation system provide a valuable source of potential biomarkers for early detection of pregnancy complications such as preeclampsia (PE). PE affects nearly 5-10% of pregnancies worldwide and is a major contributor to the maternal and neonatal mortality and morbidity. It is known that altered placental expression of matrix metalloproteinases (MMPs) may cause shallow cytotrophoblastic invasion and ultimately lead to preeclampsia. The present study aimed to evaluate pattern of placental/fetal expression of the MMP family (MMP-2, MMP-9, MMP-14, MMP-15 and MMP-26) in preeclamptic women and compare it to normal pregnancies, using cell free fetal RNA (cff-RNA). METHODS: Blood samples were obtained from 20 pregnant women diagnosed with severe PE (28-32 weeks) and 40 control healthy pregnant women in two groups of either matched gestational age (N = 20) or 14 and 28 weeks pregnancies (each 10). cff-RNA was extracted from plasma, followed by reverse transcription of cff-RNA. Expression of MMP genes was measured using quantitative reverse transcription PCR (qRT-PCR). RESULTS: The expression levels of MMP-2, MMP-9 and MMP-15 were significantly increased, while MMP-14 expression level was significantly reduced and the expression of MMP-26 showed a relative increase in PE pregnancies compared to the control group. Additionally, increased level of MMPs expression was observed by comparing 14 and 28 weeks gestation age in normal pregnancy. CONCLUSION: Using cff-RNA, circulatory expression level of MMP-2, MMP-9, MMP-14 and MMP-15 were significantly altered in preeclampsia compared to normal pregnancies.