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RESEARCH ARTICLE

Insulinotropic nucleobindin-2/nesfatin-1 is dynamically expressed in the haemochorial mouse and human placenta

Crystalyn B. Legg-St Pierre A B , Martina Mackova C , Ewa I. Miskiewicz A B , Denise G. Hemmings C , Suraj Unniappan A B and Daniel J. MacPhee A B D E
+ Author Affiliations
- Author Affiliations

A Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada.

B One Reproductive Health Research Group, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada.

C Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, 227 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, T6G 2S2, Canada.

D Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, A1B 3V6, Canada.

E Corresponding author. Email: d.macphee@usask.ca

Reproduction, Fertility and Development 30(3) 519-532 https://doi.org/10.1071/RD16486
Submitted: 3 December 2016  Accepted: 29 July 2017   Published: 31 August 2017

Abstract

The placenta is the physiological bridge between mother and fetus and has life-sustaining functions during pregnancy, including metabolic regulation, fetal protection and hormone secretion. Nucleobindin-2 (NUCB2) is a calcium- and DNA-binding protein and precursor of nesfatin-1, a signalling peptide with multiple functions, including regulation of energy homeostasis and glucose transport. These are also key functions of the placenta, yet NUCB2/nesfatin-1 expression has never been comprehensively studied in this organ. In the present study, mouse placental samples from Embryonic Day (E) 7.5 to E17.5 and human chorionic villi from the first and second trimester, as well as term pregnancy, were analysed for NUCB2/nesfatin-1 expression by immunohistochemistry with an antiserum that recognised both NUCB2 and nesfatin-1. From E7.5 to E9.5, NUCB2/nesfatin-1 was expressed in the ectoplacental cone, then parietal trophoblast giant cells and early spongiotrophoblast. At E10.5–12.5, NUCB2/nesfatin-1 expression became detectable in the developing labyrinth. From E12.5 and onwards, NUCB2/nesfatin-1 was expressed in the glycogen trophoblast cells, as well as highly expressed in syncytiotrophoblast, sinusoidal trophoblast giant cells and fetal capillary endothelial cells of the labyrinth. In all trimesters of human pregnancy, NUCB2/nesfatin-1 was highly expressed in syncytiotrophoblast. In addition, there was a significant increase in NUCB2 expression in human primary trophoblast cells induced to syncytialise. Thus, the haemochorial mammalian placenta is a novel source of NUCB2/nesfatin-1 and likely a site of its action, with potential roles in glucose homeostasis and/or nutrient sensing.

Additional keywords: labyrinth, syncytiotrophoblast, trophoblast giant cells.


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