Human Placental LRP5 and Sclerostin are Increased in Gestational Diabetes Mellitus Pregnancies

Anna Papadopoulou; Eirini Thymara; Eirini Maratou; George Kanellopoulos; Vasiliki Papaevangelou; Sophia Kalantaridou; Spyridon Kanellakis; Pinelopi Triantafyllidou; George Valsamakis; George Mastorakos

doi:10.1210/clinem/dgad164

Human Placental LRP5 and Sclerostin are Increased in Gestational Diabetes Mellitus Pregnancies

J Clin Endocrinol Metab. 2023 Sep 18;108(10):2666-2675. doi: 10.1210/clinem/dgad164.

Affiliations

¹ Third Department of Pediatrics, National and Kapodistrian University of Athens, Medical School, University General Hospital "Attikon," GR-12464, Athens, Greece.
² Department of Clinical Biochemistry, National and Kapodistrian University of Athens, Medical School, University General Hospital "Attikon," GR-12464, Athens, Greece.
³ Department of Pathology, National and Kapodistrian University of Athens, Medical School, GR-11527 Athens, Greece.
⁴ Third Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Medical School, University General Hospital "Attikon," Athens, Greece.
⁵ Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 17676 Athens, Greece.
⁶ Diabetes Mellitus and Metabolism Unit, ARETAION Hospital, Medical School, National and Kapodistrian University of Athens, GR-11528, Athens, Greece.

Abstract

Introduction: The low-density lipoprotein receptor-related protein 5 (LRP5) and its inhibitor sclerostin, are key components of bone metabolism and potential contributors to type 2 diabetes mellitus susceptibility. This study aims at evaluating the expression of placental LRP5 and sclerostin in pregnancies with gestational diabetes mellitus (GDM) and investigate possible associations with umbilical sclerostin concentrations and clinical outcomes in mothers and their neonates.

Methods: Twenty-six GDM-mothers and 34 non-GDM mothers of Caucasian origin and their neonates admitted in a gynecology and obstetrics department of a university hospital were included in this study. Demographic data and maternal fasting glucose concentrations (24-28 weeks of gestation) were retrieved from the patients' medical records. Placental LRP5 was determined by immunohistochemistry (IHC) and Western blotting analysis; placental sclerostin was determined by IHC. Umbilical serum sclerostin concentrations were measured by ELISA.

Results: Placental sclerostin IHC intensity values were positively correlated with LRP5 values as detected either by IHC (r = 0.529; P < .001) or Western blotting (r = 0.398; P = .008), with pregestational maternal body mass index values (r = 0.299; P = .043) and with maternal fasting glucose concentrations (r = 0.475; P = .009). Placental sclerostin and LRP5 were significantly greater in GDM compared with non-GDM placentas (histo-score: 65.08 ± 17.09 vs 11.45 ± 2.33, P < .001; 145.53 ± 43.74 vs 202.88 ± 58.65, P < .001; respectively).

Discussion: Sclerostin and LRP5 were detected in human placentas. The overexpression of placental sclerostin and LRP5 values in GDM compared with non-GDM pregnancies, as well as the positive association of placental sclerostin values with pregestational maternal body mass index and maternal fasting glucose concentrations may indicate the development of an adaptive mechanism in face of maternal hyperglycemia.

Keywords: LRP5; gestational diabetes mellitus; placenta; sclerostin; umbilical sclerostin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / metabolism
Diabetes, Gestational*
Female
Glucose / metabolism
Humans
Infant, Newborn
Low Density Lipoprotein Receptor-Related Protein-5 / metabolism
Placenta / metabolism
Pregnancy

Substances

Glucose
Low Density Lipoprotein Receptor-Related Protein-5
LRP5 protein, human
SOST protein, human