Survivin Expression in Placentas with Intrauterine Growth Restriction

<b>Background/Objectives:</b> Intrauterine growth restriction (IUGR) is a pathological condition defined by a reduced fetal ability to achieve the genetically expected growth potential during gestation. It affects 5–10% of all pregnancies and it is a leading cause of perinatal morbidity...

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Main Authors: Pavo Perković, Sanja Štifter-Vretenar, Marina Perković, Marko Štefančić, Ena Holjević, Andrea Dekanić, Tea Štimac
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/7/1576
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author Pavo Perković
Sanja Štifter-Vretenar
Marina Perković
Marko Štefančić
Ena Holjević
Andrea Dekanić
Tea Štimac
author_facet Pavo Perković
Sanja Štifter-Vretenar
Marina Perković
Marko Štefančić
Ena Holjević
Andrea Dekanić
Tea Štimac
author_sort Pavo Perković
collection DOAJ
description <b>Background/Objectives:</b> Intrauterine growth restriction (IUGR) is a pathological condition defined by a reduced fetal ability to achieve the genetically expected growth potential during gestation. It affects 5–10% of all pregnancies and it is a leading cause of perinatal morbidity and mortality. During the initial phases of placentation, complex interlinked processes including cell proliferation, differentiation, apoptosis and the invasion of trophoblasts occur. Alterations in the regulation of these processes lead to placental dysfunction. Survivin, a member of the inhibitor of apoptosis (IAP) family, plays an important role in cell proliferation balance and apoptosis, thus leading to proper placental development. This study aimed to evaluate survivin expression in placentas from IUGR and healthy pregnancies to explore its potential as a biomarker for the early diagnosis, prevention, and treatment of IUGR. <b>Methods</b>: Survivin presence was determined in 153 archival formalin-fixed and paraffin-embedded placental tissues from IUGR (N = 122) and uncomplicated (N = 31) term pregnancies. Tissue microarrays (TMAs) were constructed, and survivin expression was assessed using immunohistochemistry (IHC). Survivin levels were quantified using positive cell proportion (PCP) scores and immunoreactive scores (IRS), with statistical significance determined using mean values, standard deviation (SD), standard error, and Student’s t test in instances of normal distribution, and when this was not the case, the Mann–Whitney test. Chi-square tests, Fisher exact tests, and <i>t</i>-tests (<i>p</i> < 0.05) were used to compare categorical variables. <b>Results</b>: Our results suggested the significantly higher expression of survivin validated with PCP (<i>p</i> < 0.001) and IRS (<i>p</i> < 0.002) in placentas with IUGR compared to placentas from non-complicated term pregnancies. <b>Conclusions</b>: Increased survivin expression in IUGR placentas points to its potential role as a key indicator of placental dysfunction. By signaling early pathological changes, survivin may offer a valuable tool for the early detection of IUGR, potentially allowing for timely clinical interventions that could reduce the risk of serious outcomes, including stillbirth. To fully establish survivin’s clinical value, further research is needed to validate its diagnostic accuracy and to explore its involvement in molecular pathways that may be targeted for therapeutic benefit.
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spelling doaj-art-b8709fdaaa014ab8abee02873eb569e92025-08-20T03:35:58ZengMDPI AGBiomedicines2227-90592025-06-01137157610.3390/biomedicines13071576Survivin Expression in Placentas with Intrauterine Growth RestrictionPavo Perković0Sanja Štifter-Vretenar1Marina Perković2Marko Štefančić3Ena Holjević4Andrea Dekanić5Tea Štimac6Department of Gynecology and Obstetrics, University Hospital Merkur, Zajčeva 19, 10000 Zagreb, CroatiaDepartment of Pathology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 161, 8200 Aarhus, DenmarkSpecial Hospital for Pulmonary Diseases, Rockefellerova 3, 10000 Zagreb, CroatiaDepartment of Gynecology and Obstetrics, Sestre Milosrdnice University Hospital Center, Vinogradska 29, 10000 Zagreb, CroatiaDepartment of Pathology and Cytology, Clinical Hospital Centre Rijeka, Krešimirova ulica 42, 51000 Rijeka, CroatiaDepartment of Pathology and Cytology, Clinical Hospital Centre Rijeka, Krešimirova ulica 42, 51000 Rijeka, CroatiaDepartment of Gynecology and Obstetrics, Clinical Hospital Centre Rijeka, Krešimirova ulica 42, 51000 Rijeka, Croatia<b>Background/Objectives:</b> Intrauterine growth restriction (IUGR) is a pathological condition defined by a reduced fetal ability to achieve the genetically expected growth potential during gestation. It affects 5–10% of all pregnancies and it is a leading cause of perinatal morbidity and mortality. During the initial phases of placentation, complex interlinked processes including cell proliferation, differentiation, apoptosis and the invasion of trophoblasts occur. Alterations in the regulation of these processes lead to placental dysfunction. Survivin, a member of the inhibitor of apoptosis (IAP) family, plays an important role in cell proliferation balance and apoptosis, thus leading to proper placental development. This study aimed to evaluate survivin expression in placentas from IUGR and healthy pregnancies to explore its potential as a biomarker for the early diagnosis, prevention, and treatment of IUGR. <b>Methods</b>: Survivin presence was determined in 153 archival formalin-fixed and paraffin-embedded placental tissues from IUGR (N = 122) and uncomplicated (N = 31) term pregnancies. Tissue microarrays (TMAs) were constructed, and survivin expression was assessed using immunohistochemistry (IHC). Survivin levels were quantified using positive cell proportion (PCP) scores and immunoreactive scores (IRS), with statistical significance determined using mean values, standard deviation (SD), standard error, and Student’s t test in instances of normal distribution, and when this was not the case, the Mann–Whitney test. Chi-square tests, Fisher exact tests, and <i>t</i>-tests (<i>p</i> < 0.05) were used to compare categorical variables. <b>Results</b>: Our results suggested the significantly higher expression of survivin validated with PCP (<i>p</i> < 0.001) and IRS (<i>p</i> < 0.002) in placentas with IUGR compared to placentas from non-complicated term pregnancies. <b>Conclusions</b>: Increased survivin expression in IUGR placentas points to its potential role as a key indicator of placental dysfunction. By signaling early pathological changes, survivin may offer a valuable tool for the early detection of IUGR, potentially allowing for timely clinical interventions that could reduce the risk of serious outcomes, including stillbirth. To fully establish survivin’s clinical value, further research is needed to validate its diagnostic accuracy and to explore its involvement in molecular pathways that may be targeted for therapeutic benefit.https://www.mdpi.com/2227-9059/13/7/1576apoptosisintrauterine growth restrictionplacentasurvivin
spellingShingle Pavo Perković
Sanja Štifter-Vretenar
Marina Perković
Marko Štefančić
Ena Holjević
Andrea Dekanić
Tea Štimac
Survivin Expression in Placentas with Intrauterine Growth Restriction
Biomedicines
apoptosis
intrauterine growth restriction
placenta
survivin
title Survivin Expression in Placentas with Intrauterine Growth Restriction
title_full Survivin Expression in Placentas with Intrauterine Growth Restriction
title_fullStr Survivin Expression in Placentas with Intrauterine Growth Restriction
title_full_unstemmed Survivin Expression in Placentas with Intrauterine Growth Restriction
title_short Survivin Expression in Placentas with Intrauterine Growth Restriction
title_sort survivin expression in placentas with intrauterine growth restriction
topic apoptosis
intrauterine growth restriction
placenta
survivin
url https://www.mdpi.com/2227-9059/13/7/1576
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