The chimera-type galectin-3 is a positive modulator of trophoblast functions with dysregulated expression in gestational diabetes mellitus

TY - JOUR

T1 - The chimera-type galectin-3 is a positive modulator of trophoblast functions with dysregulated expression in gestational diabetes mellitus

AU - Freitag, Nancy

AU - Tirado-González, Irene

AU - Barrientos, Gabriela

AU - Cohen, Marie

AU - Daher, Silvia

AU - Goldman-Wohl, Debra

AU - Mincheva-Nilsson, Lucia

AU - John, Constance M

AU - Jeschke, Udo

AU - Blois, Sandra M

N1 - © 2020 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.

PY - 2020/12

Y1 - 2020/12

N2 - PROBLEM: From conception, a delicate regulation of galectins, a family of carbohydrate-binding proteins, is established to ensure maternal immune tolerance in pregnancy. Though galectin-3 (gal-3), the only chimera-type galectin, is abundantly expressed at the feto-maternal interface; the physiological role of this lectin during pregnancy remains to be fully elucidated and requires further investigation.METHOD OF STUDY: In this study, we analyzed serum gal-3 levels during the course of healthy gestation. Trophoblast functions were evaluated upon gal-3 exogenous stimulation using trophoblastic cell lines (e.g. , HIPEC65, SGHPL-4, and BeWo cells). Finally, we investigated variations in peripheral gal-3 levels associated with the development of spontaneous abortion and gestational diabetes mellitus (GDM).RESULTS: Gal-3 circulating levels increased as normal pregnancy progressed. In vitro experiments showed that exogenous gal-3 positively regulated trophoblast functions inducing invasion, tube formation, and fusion. Compared with normal pregnant women, circulating gal-3 levels were significantly decreased in patients who developed GDM.CONCLUSION: Our results reveal a physiological role for gal-3 during pregnancy, promoting proper trophoblast functions associated with healthy gestation. GDM is associated with a failure to increase circulating gal-3 levels late in gestation. Thus, dysregulation of gal-3 may indicate a contribution of the chimera-type lectin to this adverse pregnancy outcome.

AB - PROBLEM: From conception, a delicate regulation of galectins, a family of carbohydrate-binding proteins, is established to ensure maternal immune tolerance in pregnancy. Though galectin-3 (gal-3), the only chimera-type galectin, is abundantly expressed at the feto-maternal interface; the physiological role of this lectin during pregnancy remains to be fully elucidated and requires further investigation.METHOD OF STUDY: In this study, we analyzed serum gal-3 levels during the course of healthy gestation. Trophoblast functions were evaluated upon gal-3 exogenous stimulation using trophoblastic cell lines (e.g. , HIPEC65, SGHPL-4, and BeWo cells). Finally, we investigated variations in peripheral gal-3 levels associated with the development of spontaneous abortion and gestational diabetes mellitus (GDM).RESULTS: Gal-3 circulating levels increased as normal pregnancy progressed. In vitro experiments showed that exogenous gal-3 positively regulated trophoblast functions inducing invasion, tube formation, and fusion. Compared with normal pregnant women, circulating gal-3 levels were significantly decreased in patients who developed GDM.CONCLUSION: Our results reveal a physiological role for gal-3 during pregnancy, promoting proper trophoblast functions associated with healthy gestation. GDM is associated with a failure to increase circulating gal-3 levels late in gestation. Thus, dysregulation of gal-3 may indicate a contribution of the chimera-type lectin to this adverse pregnancy outcome.

U2 - 10.1111/aji.13311

DO - 10.1111/aji.13311

M3 - SCORING: Journal article

C2 - 32691950

VL - 84

SP - e13311

JO - AM J REPROD IMMUNOL

JF - AM J REPROD IMMUNOL

SN - 1046-7408

IS - 6

ER -