Calcifediol Decreases Interleukin-6 Secretion by Cultured Human Trophoblasts From GDM Pregnancies

Marilyn Lacroix; Farah Lizotte; Marie-France Hivert; Pedro Geraldes; Patrice Perron

doi:10.1210/js.2019-00181

Calcifediol Decreases Interleukin-6 Secretion by Cultured Human Trophoblasts From GDM Pregnancies

J Endocr Soc. 2019 Sep 5;3(11):2165-2178. doi: 10.1210/js.2019-00181. eCollection 2019 Nov 1.

Authors

Marilyn Lacroix¹, Farah Lizotte¹, Marie-France Hivert^{1

2

3}, Pedro Geraldes^{1

3}, Patrice Perron^{1

3}

Affiliations

¹ Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Science, Université de Sherbrooke, Sherbrooke, Québec, Canada.
² Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
³ Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada.

Abstract

Gestational diabetes mellitus (GDM) is often characterized by low maternal calcifediol (25OHD) and high inflammation levels. This study aimed to determine whether placental protein expressions of CYP27B1, vitamin D receptor (VDR), and CYP24A1 are impaired in GDM and to investigate the effect of a 25OHD treatment on IL-6 secretion by GDM trophoblasts compared with normoglycemic (NG) trophoblasts. Placental tissue samples were harvested to determine protein expression of CYP27B1, VDR, and CYP24A1 by immunoblots. Isolated trophoblasts were stimulated with 25OHD concentrations (25 to 2000 nM) once a day for 3 days and IL-6 secretion was quantified (ELISA). We recruited 17 NG women, 19 women with GDM treated with diet and exercise alone (GDM-d) and 9 women with GDM who necessitated insulin therapy (GDM-i). Protein expressions of CYP27B1 and VDR were significantly higher in placental tissue from GDM-d women compared with NG women (both P = 0.02), whereas no differences were detected between GDM-i and NG placental tissues. In cultured trophoblasts (two groups; n = 5 NG and n = 5 GDM-d), exposure to increasing 25OHD concentrations significantly decreased IL-6 secretion in the GDM-d group only (P = 0.006). After treatment with 25OHD (2000 nM), IL-6 secretion was lower in the GDM-d group compared with the NG group (P = 0.03). Our results suggest an upregulation of the VDR-1,25(OH)₂D complex bioavailability in GDM-d placentas, possibly reflecting a compensatory mechanism aiming to ensure that vitamin D can exert its genomic and nongenomic effects in the target cells of the placental-fetal unit. Our findings support an anti-inflammatory effect of vitamin D at the feto-maternal interface in GDM-d pregnancies.

Keywords: IL-6; gestational diabetes; inflammation; placenta; trophoblast; vitamin D.