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

1. Zamudio S. The placenta at high altitude. High Alt. Med. Biol. 2003;4:171–191

2. Ali KZ. Stereological study of the effect of altitude on the trophoblast cell populations of human term placental villi. Placenta 1997;18 :447–450

3. 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