Effect of high concentrations of glucose on differentiation of rat trophoblast cells in vitro

Abstract

Aims/hypothesis. Previous studies have shown that diabetic placentas are characterized by structural and biochemical anomalies, including defects in the differentiation of trophoblasts. In this study, the Rcho-1 cell line was used to investigate the impact of high glucose concentrations on different markers of differentiation of rat trophoblast cells in giant cells (endoreduplication, invasive phenotype and endocrine phenotype). Materials. Rcho-1 cells were incubated for 12 days in medium supplemented with different concentrations of glucose and 10% horse serum to optimize differentiation. The cells were examined for the proportion of nuclei showing signs of apoptosis. The effect of high glucose was investigated on the endoreduplication process, on invasive phenotype (secretion of gelatinase B) and on endocrine phenotype (expression of placental lactogen I (PL-I) and II (PL-II) and progesterone secretion). Results. Apoptosis was not induced by high glucose in Rcho-1. The number of cells was higher in the cultures exposed to high glucose (p<0.05) and their nuclei contained more DNA compared with control cells (p<0.001), while their nuclear size was smaller (p<0.001). Gelatinase B secretion increased during differentiation but no difference was found when gelatinase B secretion from trophoblasts exposed to high glucose was compared with the control cells. Rcho-1 cell cultures showed an increase in PL-I and PL-II mRNA expressions during differentiation and which was not affected by high glucose. Progesterone secretion increased during differentiation in control cultures. However, this increase was abolished when trophoblasts were cultured in high glucose. Conclusions/interpretation. Our data suggest that high glucose influences the endoreduplication process and the steroidogenesis during differentiation of rat trophoblasts. [Diabetologia (2003) 46:276-283]

Effects of intermittent high glucose on BeWo choriocarcinoma cells in culture

“…The very low level of apoptosis that we observed in cells grown under continuous high‐glucose conditions is consistent with previous reports that high glucose does not cause apoptosis in trophoblastic cells 4,27 . In our study, continuous high‐glucose conditions only slightly increased the number of TUNEL‐positive cells compared to that under control glucose conditions, and no difference in fractin staining was observed between the continuous high‐glucose and control cultures.…”

“…Fluctuations in glucose levels during pregnancy have been suggested to be associated with complications such as pre-eclampsia or FGR. Although continuously elevated glucose is toxic to trophoblast cells in culture 4,5 and affects trophoblast function, [22][23][24][25][26][27][28][29][30][31] the effect of fluctuating glucose levels on trophoblast function is unclear. In this study, we showed that culture of a human placental choriocarcinoma cell line in the presence of intermittent high glucose decreased cell proliferation and cell viability, enhanced apoptosis and specifically promoted the expression of the antiapoptotic HB-EGF.…”

Hyperglycemia perturbs biochemical networks in human trophoblast BeWo cells

“…In this study, we investigated whether HG during the differentiation process affects trophoblast gene expression. Sustained HG in cell culture has frequently been used as an in vitro model system to mimic diabetes or diabetes-like conditions [4,5,21]. The glucose concentration of 25 mM used in this study can realistically be observed in uncontrolled diabetic gravidas [22].…”

“…Glucose was suggested to be an important regulator of trophoblast invasiveness, and HG was suggested to inhibit the invasiveness of trophoblasts [4]. Hinck et al reported that HG influences the endoreduplication process and steroidogenesis during differentiation of rat trophoblast Rcho-1 cells [5]. Sustained hyperglycemia in vitro down-regulates the glucose transport system in cultured human term placental trophoblasts [21].…”

“…Type I diabetes mellitus during pregnancy is associated with dysregulation of glucose metabolism, which affects placental villous growth and function [4]. High glucose (HG) also influences the endoreduplication process and steroidogenesis during differentiation of rat trophoblast cells [5].…”