Pluripotency Stem Cell Marker Expression and Apoptotic Changes in Placental Tissues of Normal and Intra-Uterine Growth Restriction (IUGR) Babies of Iraqi Mothers: A Comparative Study

Khalida Ibrahim Noel; Hayder Hamed Abdulateef; Nibras Hatim Khamees

doi:10.54133/ajms.v8i1.1642

Authors

Khalida Ibrahim Noel Department of Human Anatomy, College of Medicine, Mustansiriyah University, Baghdad, Iraq https://orcid.org/0000-0001-6135-7087
Hayder Hamed Abdulateef Department of Human Anatomy, College of Medicine, Mustansiriyah University, Baghdad, Iraq https://orcid.org/0000-0001-5194-7075
Nibras Hatim Khamees Department of Human Anatomy, College of Medicine, Mustansiriyah University, Baghdad, Iraq https://orcid.org/0000-0002-9406-0893

DOI:

https://doi.org/10.54133/ajms.v8i1.1642

Keywords:

CASP3, IUGR, NANOG, Placenta, Pregnancy

Abstract

Background: The placenta is a vital organ for embryo development, providing nutrition, waste elimination, and communication with the mother. It also facilitates nutrient transfer and stem cell creation. Intrauterine growth restriction (IUGR) can impact the unborn child's growth during pregnancy. Objective: To examine the immunohistochemical expression of NANOG and CASP3 in both normal and IUGR placental tissues. Methods: The study involved 90 healthy mothers and their babies at 38-40 weeks of pregnancy. Doppler ultrasonography confirmed idiopathic fetal IUGR. Placentas were categorized into control and IUGR groups, with each tissue block immunohistochemically stained for NANOG and CASP3 markers. Results: Expression of the NANOG antibody in placental tissue of both normal and IUGR cases revealed a low intensity of expression in both normal and IUGR placentae and not significantly different. The expression of the CASP3 marker showed statistically significant results regarding staining intensity, percentage, and total score calculation between the normal and IUGR cases. It was of low intensity in most normal cases compared to the strong intensity of marker expression in most IUGR cases. Conclusions: Embryonic stem cells showed a diminished expression by NANOG in placentae of both normal and IUGR cases attributed to the trimester of pregnancy that decreased its expression in the third trimester generally as the stem cells become less evident as we go through the trimesters of pregnancy. On the other hand, apoptosis is one of the important changes associated with placental pathology like IUGR.

Downloads

Download data is not yet available.

References

Guttmacher AE, Maddox YT, Spong CY. The human placenta project: placental structure, development, and function in real time. Placenta. 2014;35(5):303-304. doi: 10.1016/j.placenta.2014.02.012. DOI: https://doi.org/10.1016/j.placenta.2014.02.012

Ortega MA, Fraile-Martínez O, García-Montero C, Sáez MA, Álvarez-Mon MA, Torres-Carranza D, et al. The pivotal role of the placenta in normal and pathological pregnancies: A focus on preeclampsia, fetal growth restriction, and maternal chronic venous disease. Cells. 2022;11(3):568. doi: 10.3390/cells11030568. DOI: https://doi.org/10.3390/cells11030568

Chia WK, Cheah FC, Abdul Aziz NH, Kampan NC, Shuib S, Khong TY, et al. A review of placenta and umbilical cord-derived stem cells and the immunomodulatory basis of their therapeutic potential in bronchopulmonary dysplasia. Front Pediatr. 2021;9:615508. doi: 10.3389/fped.2021.615508. DOI: https://doi.org/10.3389/fped.2021.615508

Zhang S, Regnault TR, Barker PL, Botting KJ, McMillen IC, McMillan CM, et al. Placental adaptations in growth restriction. Nutrients. 2015;7(1):360-389. doi: 10.3390/nu7010360. DOI: https://doi.org/10.3390/nu7010360

Fasoulakis Z, Koutras A, Antsaklis P, Theodora M, Valsamaki A, Daskalakis G, et al. Intrauterine growth restriction due to gestational diabetes: From pathophysiology to diagnosis and management. Medicina (Kaunas). 2023;59(6):1139. doi: 10.3390/medicina59061139. DOI: https://doi.org/10.3390/medicina59061139

Fink SL, Cookson BT. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun. 2005;73(4):1907-1916. doi: 10.1128/IAI.73.4.1907-1916.2005. DOI: https://doi.org/10.1128/IAI.73.4.1907-1916.2005

Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516. doi: 10.1080/01926230701320337. DOI: https://doi.org/10.1080/01926230701320337

Jiao Y, Cao F, Liu H. Radiation-induced cell death and its mechanisms. Health Phys. 2022;123(5):376-386. doi: 10.1097/HP.0000000000001601. DOI: https://doi.org/10.1097/HP.0000000000001601

Oberhammer F, Wilson JW, Dive C, Morris ID, Hickman JA, Wakeling AE, et al. Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. EMBO J. 1993;12(9):3679-3684. doi: 10.1002/j.1460-2075.1993.tb06042.x. DOI: https://doi.org/10.1002/j.1460-2075.1993.tb06042.x

Oberhammer FA, Hochegger K, Fröschl G, Tiefenbacher R, Pavelka M. Chromatin condensation during apoptosis is accompanied by degradation of lamin A+B, without enhanced activation of cdc2 kinase. J Cell Biol. 1994;126(4):827-837. doi: 10.1083/jcb.126.4.827. DOI: https://doi.org/10.1083/jcb.126.4.827

Noel KI, Khamees NH, Abdulateef HH. Assessment of the effect of glucocorticoid injections on the expression of apoptotic active CASP3 and ALDH1A1 renal cell markers in New Zealand rabbits. Eastern J Med. 2024;29(4):397-405. doi: 10.5505/ejm.2024.39049. DOI: https://doi.org/10.5505/ejm.2024.39049

Sharp AN, Heazell AE, Crocker IP, Mor G. Placental apoptosis in health and disease. Am J Reprod Immunol. 2010;64(3):159-169. doi: 10.1111/j.1600-0897.2010.00837.x.

Smith SC, Baker PN, Symonds EM. Increased placental apoptosis in intrauterine growth restriction. Am J Obstet Gynecol. 1997;177(6):1395-1401. doi: 10.1016/s0002-9378(97)70081-4.

Ponder KG, Boise LH. The prodomain of caspase-3 regulates its own removal and caspase activation. Cell Death Discov. 2019;5:56. doi: 10.1038/s41420-019-0142-1. DOI: https://doi.org/10.1038/s41420-019-0142-1

Abdulateef HH, Shukri EG, Ahmed BS. Immunohistopathological co-expression of NANOG and OCT4 in normal tissue around papillary thyroid cancer and multinodular goiter. Biochem Cell Arch. 2020;20(2):4477-4485.

Zhang W, Ni P, Mou C, Zhang Y, Guo H, Zhao T, et al. Cops2 promotes pluripotency maintenance by stabilizing nanog protein and repressing transcription. Sci Rep. 2016;6:26804. doi: 10.1038/srep26804. DOI: https://doi.org/10.1038/srep26804

Hambiliki F, Ström S, Zhang P, Stavreus-Evers A. Co-localization of NANOG and OCT4 in human pre-implantation embryos and in human embryonic stem cells. J Assist Reprod Genet. 2012;29(10):1021-1028. doi: 10.1007/s10815-012-9824-9. DOI: https://doi.org/10.1007/s10815-012-9824-9

Al-Kaabi M, Noel K, Al-Rubai A. Evaluation of immunohistochemical expression of stem cell markers (NANOG and CD133) in normal, hyperplastic, and malignant endometrium. J Med Life. 2022;15(1):117-123. doi: 10.25122/jml-2021-0206. DOI: https://doi.org/10.25122/jml-2021-0206

Novac MV, Iliescu DG, Tudorache S, Manolea M, Meetescu RE, Vrabie S, et al. Ultrasound evaluation of fetal biometry and doppler parameters in the third trimester of pregnancy suspected of intrauterine growth restriction. Curr Health Sci J. 2018;44(1):23-28. doi: 10.12865/CHSJ.44.01.04.

Al-Rubai A, Mohammed IM, Fakhir HA, Noel K, Eleiwi SA. Comparison of placental expression of basic fibroblast growth factor and insulin-like growth factor-1 in placentae of normal, pregnancy-induced hypertension, and preeclamptic pregnancies in Iraqi mothers. Med J Babylon. 2023;20(4):681-688. doi: 10.4103/MJBL.MJBL_40_23. DOI: https://doi.org/10.4103/MJBL.MJBL_40_23

Hameed AF, Noel KI, Akkila SS. Placental angiogenesis, IUGR & CMV awareness in Iraqi women. Curr Issues Pharm Med Sci. 2022;35(3):147-151. doi: 10.2478/cipms-2022-0027. DOI: https://doi.org/10.2478/cipms-2022-0027

Noel KI, Ibraheem MM, Ahmed BS, Hameed AF, Khamees NH, Akkila SS. Expression of OCT4 stem cell marker in benign prostatic hyperplasia and normal tissue around the prostatic carcinoma in a sample of Iraqi patients. Egypt J Histol. 2020;43(1):245-254. doi: 10.21608/ejh.2019.13791.1130. DOI: https://doi.org/10.21608/ejh.2019.13791.1130

Noel KI, Ibraheem MM, Ahmed BS, Hameed AF, Khamees NH, Akkila SS. CD133 and CD166 expression predicting the possibility of prostatic cancer development in cases of BPH. Biomed Pharmacol J. 2019;12(3):1403-1416. doi: 10.13005/bpj/1769. DOI: https://doi.org/10.13005/bpj/1769

Weber M, Göhner C, San Martin S, Vattai A, Hutter S, Parraga M, et al. Unique trophoblast stem cell- and pluripotency marker staining patterns depending on gestational age and placenta-associated pregnancy complications. Cell Adh Migr. 2016;10(1-2):56-65. doi: 10.1080/19336918.2016.1142035. DOI: https://doi.org/10.1080/19336918.2016.1142035

Kaufmann P, Black S, Huppertz B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod. 2003;69(1):1-7. doi: 10.1095/biolreprod.102.014977. DOI: https://doi.org/10.1095/biolreprod.102.014977

Levy R, Nelson DM. To be, or not to be, that is the question. Apoptosis in human trophoblast. Placenta. 2000;21(1):1-13. doi: 10.1053/plac.1999.0450. DOI: https://doi.org/10.1053/plac.1999.0450

Stepan H, Leo C, Purz S, Höckel M, Horn LC. Placental localization and expression of the cell death factors BNip3 and Nix in preeclampsia, intrauterine growth retardation and HELLP syndrome. Eur J Obstet Gynecol Reprod Biol. 2005;122(2):172-176. doi: 10.1016/j.ejogrb.2005.01.017. DOI: https://doi.org/10.1016/j.ejogrb.2005.01.017

Levy R, Smith SD, Yusuf K, Huettner PC, Kraus FT, Sadovsky Y, et al. Trophoblast apoptosis from pregnancies complicated by fetal growth restriction is associated with enhanced p53 expression. Am J Obstet Gynecol. 2002;186(5):1056-1061. doi: 10.1067/mob.2002.122250. DOI: https://doi.org/10.1067/mob.2002.122250

DiFederico E, Genbacev O, Fisher SJ. Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall. Am J Pathol. 1999;155(1):293-301. doi: 10.1016/S0002-9440(10)65123-1. DOI: https://doi.org/10.1016/S0002-9440(10)65123-1

Allaire AD, Ballenger KA, Wells SR, McMahon MJ, Lessey BA. Placental apoptosis in preeclampsia. Obstet Gynecol. 2000;96(2):271-276. doi: 10.1016/s0029-7844(00)00895-4. DOI: https://doi.org/10.1097/00006250-200008000-00022

Smith SC, Baker PN, Symonds EM. Increased placental apoptosis in intrauterine growth restriction. Am J Obstet Gynecol. 1997;177(6):1395-1401. doi: 10.1016/s0002-9378(97)70081-4. DOI: https://doi.org/10.1016/S0002-9378(97)70081-4

Mayhew TM, Huppertz B, Kaufmann P, Kingdom JC. The 'reference trap' revisited: examples of the dangers in using ratios to describe fetoplacental angiogenesis and trophoblast turnover. Placenta. 2003;24(1):1-7. doi: 10.1053/plac.2002.0878. DOI: https://doi.org/10.1053/plac.2002.0878

Huppertz B, Kingdom J, Caniggia I, Desoye G, Black S, Korr H, et al. Hypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation. Placenta. 2003;24(2-3):181-190. doi: 10.1053/plac.2002.0903. DOI: https://doi.org/10.1053/plac.2002.0903

Aban M, Cinel L, Arslan M, Dilek U, Kaplanoglu M, Arpaci R, et al. Expression of nuclear factor-kappa B and placental apoptosis in pregnancies complicated with intrauterine growth restriction and preeclampsia: an immunohistochemical study. Tohoku J Exp Med. 2004;204(3):195-202. doi: 10.1620/tjem.204.195. DOI: https://doi.org/10.1620/tjem.204.195

Ishihara N, Matsuo H, Murakoshi H, Laoag-Fernandez JB, Samoto T, Maruo T. Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am J Obstet Gynecol. 2002;186(1):158-166. doi: 10.1067/mob.2002.119176. DOI: https://doi.org/10.1067/mob.2002.119176

Kadyrov M, Schmitz C, Black S, Kaufmann P, Huppertz B. Pre-eclampsia and maternal anaemia display reduced apoptosis and opposite invasive phenotypes of extravillous trophoblast. Placenta. 2003;24(5):540-548. doi: 10.1053/plac.2002.0946. DOI: https://doi.org/10.1053/plac.2002.0946

Ghanem ME, Eleiwe SA, Tayeh NK. Association of idiopathic IUGR with placental histological morphometry. Indian J Public Health Res Dev. 2019;10(7):943-948. doi: 10.5958/0976-5506.2019.01699.1. DOI: https://doi.org/10.5958/0976-5506.2019.01699.1

Ghanem ME, Eleiwe SA. Expression of e-NOS in human placentas of idiopathic intra uterine growth restriction at term. Medico-Legal Update. 2020;20(1):440-445. doi: 10.37506/v20/i1/2020/mlu/194660.

Sharp AN, Heazell AE, Crocker IP, Mor G. Placental apoptosis in health and disease. Am J Reprod Immunol. 2010;64(3):159-169. doi: 10.1111/j.1600-0897.2010.00837.x. DOI: https://doi.org/10.1111/j.1600-0897.2010.00837.x

Noel KI. A reciprocal relationship between oxidative stress, antioxidants, and cancer: A review. Siriraj Med J. 2024;76(8):550-556. doi: 10.33192/smj.v76i8.268647. DOI: https://doi.org/10.33192/smj.v76i8.268647