Placental Apoptosis in Small for Gestational Age Babies: A Comparison between Swedish and Pakistani Populations
DOI:
https://doi.org/10.6000/1929-4247.2014.03.02.5Keywords:
SGA, AGA, Apoptosis, Caspase 3, Caspase 8.Abstract
Background: Foeto-placental growth is regulated by a complex balance of growth promoting and growth inhibiting factors and hormones, namely the insulin-like growth factors (IGF) and the intracellular caspase proteins. Changes in the IGF-axis appear to affect this balance, with deficiencies possibly triggering apoptosis.
Aim: To ascertain levels of apoptosis in the placenta of infants born small for gestational age (SGA) and appropriate for gestational age (AGA), comparing samples from two population groups, Pakistani and Swedish, in an attempt to better understand the mechanism behind foetal-placental growth restriction.
Methods: Placental samples were taken immediately following delivery in both Karachi and Stockholm. In total 36 samples were included for further analysis (Pakistani: SGA n = 12, AGA n = 12; Swedish: SGA n = 7, AGA n = 5). Protein extraction was conducted for cell-death ELISA, and the remaining tissue samples were then paraffin embedded for further immunohistochemical and immunoflourescent analysis, looking at the apoptotic proteins, p53, caspase 8, and caspase 3. Furthermore, we compared maternal and newborn anthropometry between populations.
Results: A higher apoptotic index, for caspase 8 and caspase 3, was seen in the Pakistani samples, as compared to the Swedish samples (p<0.01). TUNEL assays showed higher levels of apoptosis in the Pakistani population as compared to the Swedish population (p<0.01). Cell death ELISA analysis showed greater apoptotic activity in placenta from the Pakistani population as compared to the Swedish groups (p<0.05) as well as increased apoptotic activity in the SGA groups as compared to the AGA groups within each population (ELISA, p<0.05). No differences were seen in p53 levels as assessed by immunohistochemistry. Pakistani mothers were, on average, shorter than their Swedish counterparts (p<0.01).
Conclusion: Increased apoptotic activity in placenta of the Pakistani population, as compared to their Swedish counterparts, may be associated with decreased foetal-placental growth seen in this population, particularly in babies born SGA. These findings, along with previously published results of the IGF-axis, and birth weight outcomes, suggests that lower IGF levels may be involved in the extracellular triggering of apoptosis, through caspase 8. This may further suggest a possible mechanism of foetal-placental growth restriction.
References
de Onis M, Blossner M, Villar J. Levels and patterns of intrauterine growth retardation in developing countries. Eur J Clin Nutr 1998; 52(Suppl 1): S5-15.
Haram K, Gjelland K. [Foetal growth retardation]. Tidsskr Nor Laegeforen 2007; 127(20): 2665-9.
Fowden AL. The insulin-like growth factors and feto-placental growth. Placenta 2003; 24(8-9): 803-12. http://dx.doi.org/10.1016/S0143-4004(03)00080-8
Chatelain P. Children born with intra-uterine growth retardation (IUGR) or small for gestational age (SGA): long term growth and metabolic consequences. Endocr Regul 2000; 34(1): 33-6.
Austgulen R, Isaksen CV, Chedwick L, Romundstad P, Vatten L, Craven C. Pre-eclampsia: associated with increased syncytial apoptosis when the infant is small-for-gestational-age. J Reprod Immunol 2004; 61(1): 39-50. http://dx.doi.org/10.1016/j.jri.2003.10.001
Randhawa R, Cohen P. The role of the insulin-like growth factor system in prenatal growth. Mol Genet Metab 2005; 86(1-2): 84-90. http://dx.doi.org/10.1016/j.ymgme.2005.07.028
Jin Z, El-Deiry WS. Overview of cell death signaling pathways. Cancer Biol Ther 2005; 4(2): 139-63. http://dx.doi.org/10.4161/cbt.4.2.1508
Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. Nature 1997; 389(6648): 300-5. http://dx.doi.org/10.1038/38525
Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science 1998; 281(5381): 1305-8. http://dx.doi.org/10.1126/science.281.5381.1305
Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ 1999; 6(2): 99-104. http://dx.doi.org/10.1038/sj.cdd.4400476
Akram SK, Sahlin L, Ostlund E, Hagenas L, Fried G, Soder O. Placental IGF-I, estrogen receptor, and progesterone receptor expression, and maternal anthropometry in growth-restricted pregnancies in the Swedish population. Horm Res Paediatr 2011; 75(2): 131-7. http://dx.doi.org/10.1159/000320466
Akram SK, Carlsson-Skwirut C, Bhutta ZA, Soder O. Placental IGF-I, IGFBP-1, zinc, and iron, and maternal and infant anthropometry at birth. Acta Paediatr 2011; 100(11): 1504-9. http://dx.doi.org/10.1111/j.1651-2227.2011.02336.x
Proos LA. Anthropometry in adolescence--secular trends, adoption, ethnic and environmental differences. Horm Res 1993; 39(Suppl 3): 18-24. http://dx.doi.org/10.1159/000182781
Gluckman PD, Hanson MA. Maternal constraint of fetal growth and its consequences. Semin Fetal Neonatal Med 2004; 9(5): 419-25. http://dx.doi.org/10.1016/j.siny.2004.03.001
Visscher PM. Sizing up human height variation. Nat Genet 2008; 40(5): 489-90. http://dx.doi.org/10.1038/ng0508-489
Agata KB, Anita S, Urszula KK, Agnieszka NK, Grzegorz B. Expression of caspase-3, Bax nad Bcl-2 in placentas from pregnancies complicated by treated and non-treated fetal growth restriction. Ginekol Pol 2009; 80(9): 652-6.
Barrio E, Calvo MT, Miramar MD, Lorente F, Rodriguez A, Labarta JI, et al. Study of apoptosis and related proteins, CRH and hpGH in placentas of newborns small for gestational age (SGA). Pediatr Endocrinol Rev 2009; 6(Suppl 3): 337-42.
Amaral JD, Xavier JM, Steer CJ, Rodrigues CM. Targeting the p53 pathway of apoptosis. Curr Pharm Des 2010; 16(22): 2493-503. http://dx.doi.org/10.2174/138161210791959818
Halperin R, Peller S, Sandbank J, Bukovsky I, Schneider D. Expression of the p53 gene and apoptosis in gestational trophoblastic disease. Placenta 2000; 21(1): 58-62. http://dx.doi.org/10.1053/plac.1999.0442
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): 1056-61. http://dx.doi.org/10.1067/mob.2002.122250
Akram SK, Akram M, Bhutta ZA, Soder O. Human placental IGF-I and IGF-II expression: correlating maternal and infant anthropometric variables and micronutrients at birth in the Pakistani population. Acta Paediatr 2008; 97(10): 1443-8. http://dx.doi.org/10.1111/j.1651-2227.2008.00930.x
Ain R, Canham LN, Soares MJ. Dexamethasone-induced intrauterine growth restriction impacts the placental prolactin family, insulin-like growth factor-II and the Akt signaling pathway. J Endocrinol 2005; 185(2): 253-63. http://dx.doi.org/10.1677/joe.1.06039
Laviola L, Natalicchio A, Giorgino F. The IGF-I signaling pathway. Curr Pharm Des 2007; 13(7): 663-9. http://dx.doi.org/10.2174/138161207780249146
Litton C, Stone J, Eddleman K, Lee MJ. Noninvasive prenatal diagnosis: past, present, and future. Mt Sinai J Med 2009; 76(6): 521-8. http://dx.doi.org/10.1002/msj.20153
Downloads
Published
How to Cite
Issue
Section
License
Policy for Journals/Articles with Open Access
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work
Policy for Journals / Manuscript with Paid Access
Authors who publish with this journal agree to the following terms:
- Publisher retain copyright .
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work .
