Background: Delta-Like Homologue 1 (DLK1) is a gene encoding a transmembrane protein, which may also be secreted into the circulation. DLK1 levels are known to rise in maternal serum during late gestation and our genetic studies in the mouse have shown that this DLK1 arises from the conceptus. However, the cell population that secretes DLK1 into the maternal circulation has not been identified. Since DLK1 has been shown to be differentially expressed in intrauterine growth restricted when compared with normal human placentas, it may be an important biomarker of placental function and foetal development.
Objective and Hypotheses: Our objective is to find the source population of DLK1-secreting cells in the placenta. We hypothesise that maternal serum levels of DLK1 derived from the conceptus may reflect indices of foetal and placental growth.
Method: 45 women were recruited from our obstetric department and followed up prospectively. Measurements of foetal growth parameters (abdominal circumference (AC), femoral length, and biparietal diameter), maternal clinical information and maternal serum samples were collected at 20, 28, 34, and 38 weeks gestation. DLK1 ELISA analyses were performed on the serum samples. DLK1 immunohistochemistry was carried out on placental samples in combination with histological and immunocytochemical markers of placental cell populations.
Results: We were able to localise DLK1 expression to multiple cell populations within the mature placental villi including the foetal endothelium and the trophoblast compartments. Maternal DLK1 levels rise during gestation and fall post-delivery. The rate of this rise is seen to be highest between 28 and 34 weeks gestation, coincident with the increase of the foetal AC.
Conclusion: We localised DLK1 in the term placenta to an endocrine cell population, consistent with its secretion into the maternal circulation from this tissue. In addition, our longitudinal study of DLK1 in maternal serum during normal pregnancy suggests that DLK1 levels reflect rates of foetal growth.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology