Dissertation committee:
Ομότ. Καθηγήτρια Πολυξένη Νικολαϊδου Καρπαθίου, Ομοτ. Καθηγητής Εμμανουήλ Σαλαμαλέκης, Ομοτ. Καθηγητής Ανδρέας Φρετζαγιάς
Summary:
Introduction: Infants born from mothers with Gestational diabetes mellitus
(GDM) experience several complications, including a higher rate of postnatal
hypocalcemia. In this study, we investigated the association between Calcium
Sensing Receptor (CaSR) and neonatal hypocalcemia observed in GDM pregnancies.
Methods: Our study consisted of 58 pregnant women with GDM and 40 healthy women
and their neonates. CaSR placental expression was evaluated with
immunohistochemistry and Western Blot. Three CaSR single nucleotide
polymorphisms, A986S, R990G, Q1011E, were evaluated in neonate’s genomic DNA.
Serum Calcium (Ca), P, Mg, 25(OH)D and PTH were measured in cord blood and at
2nd day of life.
Results: GDM neonates had lower mean cord blood Ca levels than controls (9,87±0,
86 mg/dl vs 10,39±0,53 mg/dl, p=0,001) while 15,5% developed postnatal
hypocalcemia. CaSR expression was lower in GDM than in healthy placentas
(p<0,001). In the GDM group, reduced CaSR immunostaining was associated with
lower Ca cord blood levels, in syncytiotrophoblasts (p=0,042) and extravillous
cytotrophoblasts (p=0,002). Moreover, the absence of the S allele of the A986S
polymorphism was associated with lower serum Ca levels both at birth (AA:
9,64±0,2 mg/dl, AS+SS: 10,31±0,47 mg/dl, p=0,002) and at 2nd day of life (AA:
8,22±0,9 mg/dl, AS+SS: 8,82±0,71 mg/dl, p=0,019).
Conclusions: Our results showed that CaSR is under-expressed in GDM compared
with healthy placentas and this alteration may be associated with the lower Ca
levels measured in cord blood of GDM infants. Placental CaSR seems to exert a
local effect in fetal Ca homeostasis, which is dissociated from its
contribution to the regulation of Ca homeostasis in postnatal life.
Keywords:
Calcium sensing receptor , CASR, Hypocalcaemia, Gestational diabetes mellitus, Placenta
