Sugar-Specific Modulation of Trophoblast Function and Bioenergetics Under Metabolic Stress Conditions

How sugars other than glucose affect trophoblast function is poorly understood, particularly under the metabolic stress of diabetic pregnancy. We compared glucose, fructose, and the minimally metabolized sugar allulose in two trophoblast cell lines, SW71 (first-trimester, extravillous-like) and BeWo (choriocarcinoma-derived, villous). Each sugar was added at 25 mM for 24 h to the cells' standard glucose-containing media (11 mM, SW71; 17.5 mM, BeWo) to model metabolic stress. All three sugars increased the number of cells recovered (2.4- to 6.5-fold in SW71; ~10- to 15-fold in BeWo) and reduced viability (~9-75%), with fructose causing the largest loss in both lines. Intracellular reactive oxygen species increased 5.2- to 7.8-fold with all sugars. Oxygen consumption differed by sugar: in SW71 cells, glucose and allulose increased ADP-stimulated and succinate-supported respiration, whereas fructose reduced it, and in BeWo cells only fructose increased it. SW71 invasion was ~7-fold higher after allulose than after glucose or fructose. BeWo cells were studied undifferentiated, so effects on syncytialization were not assessed. The three sugars are therefore not interchangeable in their effects on trophoblast cells in vitro. Because the concentrations exceed those in maternal blood, these findings are hypothesis-generating and require testing at physiological concentrations and in primary trophoblast models.