PPO.20 The effect of high altitude on cell proliferation, apoptosis and fusion in the human placenta. (9th June 2014)

• Record Type: Journal Article
• Authors: CESA, Jackson; Cindrova-Davies, T; Burton, GJ
• Is Part Of: Archives of disease in childhood. Volume 99:Supplement 1(2014)
• Page Start: A156
• Page End: A160
• Publication Date: 2014-06-09
• Subjects: Infants -- Diseases -- Periodicals; Newborn infants -- Diseases -- Periodicals; Fetus -- Diseases -- Periodicals; 618.920105
• DOI: 10.1136/archdischild-2014-306576.460
• Languages: English
• ISSNs: 1359-2998

Abstract

Abstract : Background: High-altitude pregnancy is a natural model for the effects of chronic mild hypobaric hypoxia on placental and fetal growth. Hypoxia is an important cause of complications of pregnancy e.g. intrauterine growth restriction. 1 Hypoxia increases cytotrophoblast (CTB) proliferation and apoptosis and decreases fusion in vitro . However, controversy exists over its effects in vivo . 2, 3 For the first time, this study investigated the effect of high-altitude on cell proliferation, apoptosis and fusion in normal term placentae from non-native women living at sea-level (London) and high-altitude (Leadville, Colorado; 3100 m). Method: Sequential sections from ten placentae were stained for markers of proliferation (Ki67, PCNA), apoptosis (Cleaved Caspase-3) and fusion (a-HERV-FRD-1) using immunohistochemistry. The numbers of CTB and syncytiotrophoblast (STB) nuclei staining positively and negatively for each antibody were counted using the unbiased physical disector technique. Results: There was no significant difference between the proportions of CTB undergoing proliferation (Ki67 p = 0.683; PCNA p = 0.683); apoptosis (CCasp-3 p = 0.905); or fusion (a-HERV-FRD-1 p = 0.905) at sea-level and high-altitude. No STB stained positively for Ki67 or CCasp-3. Equally, there were no significant differences in mean numerical densities of CTB (p = 0.873) or STB (p = 0.683); total number of nuclei (CTB p = 0.873; STB p = 0.524); STB:CTB (p = 0.542); placental weight (p = 0.405); placental volume (p = 0.405); birthweight (p = 0.417); or placental index (p = 0.191). Conclusion: High-altitude does not cause a significant difference in the proportions of CTB undergoing proliferation, apoptosis or fusion in normal term placentae from non-native women. Proliferation and apoptosis occur in CTB, not STB. Fusion of CTB to STB is rare in term placentae. References: Zamudio S. The placenta at high altitude. High Alt. Med. Biol. 2003;4:171–191 Ali KZ. Stereological study of the effect of altitude on the trophoblast cell populations of human term placental villi. Placenta 1997;18 :447–450 Yung HW, Cox M, Tissot van Patot M. & Burton GJ. Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude. Faseb J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2012;26:1970–1981