Energy metabolism and glycolysis in human placental trophoblast cells during differentiation

Abstract

Energy metabolism and glycolysis of normal human term placental trophoblast in two-sided culture was investigated during differentiation from cytotrophoblast to syncytiotrophoblast, because glycogen metabolism is abnormal in several trophoblast related pregnancy diseases, including pre-eclampsia. After initial recovery of energy and cytoplasmic NADH/NAD+ redox by 24 h of culture, measures of cellular energy state, [ATP], [ADP], [ATP]/[ADP] ratio, ([ATP] + [ADP] + [AMP]), [ATP]/([ATP] + [ADP] + [AMP]) and energy charge remained essentially constant until 72 h, despite periods of increased energy turnover. At 24 h there was a burst of glycogenolysis, and glycolysis indicated by increased lactate production, which coincided with formation of syncytium. Subsequently, there was no resynthesis nor further breakdown of glycogen. At 48 h, oxygen consumption temporarily increased substantially, without increased glycolysis, during functional differentiation of the syncytiotrophoblast. Glucose uptake was constant and largely from the basal (in vivo fetal facing) side. Lactate output into the basal fetal medium was twice as fast as that into the microvillous (maternal) medium, and oxygen uptake was also asymmetrical. The results show that before and after differentiation substantial relatively constant aerobic glycolysis occurs, but that during increased energy demand cytotrophoblast depends on both glycolytic and aerobic energy production whereas syncytiotrophoblast relies on aerobic metabolism.

Osteoclast Precursors Display Dynamic Metabolic Shifts toward Accelerated Glucose Metabolism at an Early Stage of RANKL-Stimulated Osteoclast Differentiation

“…Together, these results demonstrate that a simultaneous activation of glycolytic and oxidative metabolism is necessary for efficient energy and biosynthetic substrate production from glucose. The present findings agree with previous reports that oxidative phosphorylation is increased to support high ATP demands during differentiation of various cell types, including human placental trophoblasts, nerve cells, and human colon adenocarcinoma cells [24][25][26].…”

A role for the mitochondrial-associated protein p32 in regulation of trophoblast proliferation

“…The majority of tissues use oxidative phosphorylation to generate ATP under aerobic conditions; however, the placenta also generates ATP via aerobic glycolysis, which is characterized by high rates of conversion of glucose to lactate and increased glucose uptake (Bloxam and Bobinski, 1984; Bax and Bloxam, 1997). Knockdown of p32 in tumour cell lines was associated with enhanced glycolysis and increased glucose uptake and lactate production (Fogal et al , 2010).…”

Maternal–fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer

“…Shared features include rapid proliferation, invasion of neighbouring tissues, deportation to distant sites, vasculogenic mimicry, induction of angiogenesis and modulation of immune responses [18 -21]. Trophoblast and malignant cells both use aerobic glycolysis [22,23] and many cancers express 'trophoblast-specific' genes [24][25][26][27]. The b-subunit of chorionic gonadotropin (CGb) is a quintessential product of trophoblast that is expressed by many trophoblastic and non-trophoblastic tumours [14,28] and has been considered a 'definitive cancer biomarker' [16].…”