Fructose Synthesis and Transport at the Uterine-Placental Interface of Pigs: Cell-Specific Localization of SLC2A5, SLC2A8, and Components of the Polyol Pathway

Abstract

The fetal fluids and uterine flushings of pigs contain higher concentrations of fructose than glucose, but fructose is not detected in maternal blood. Fructose can be synthesized from glucose via enzymes of the polyol pathway, aldose reductase (AKR1B1) and sorbitol dehydrogenase (SORD), transported across cell membranes by solute carriers SLC2A5 and SLC2A8, and converted to fructose-1-phosphate by ketohexokinase (KHK). SLC2A8, SLC2A5, AKR1B1, SORD, and KHK mRNAs and proteins were analyzed using quantitative PCR and immunohistochemistry or in situ hybridization in endometria and placentae of cyclic and pregnant gilts, cyclic gilts injected with estrogen, and ovariectomized gilts injected with progesterone. Progesterone up-regulated SLC2A8 protein in uterine luminal (LE) and glandular epithelia during the peri-implantation period, and expression became exclusively placental, chorion and blood vessels, after Day 30. P4 up-regulated SLC2A5 mRNA in uterine LE and glandular epithelia after implantation, and the chorion expressed SLC2A5 between Days 30 and 85. AKR1B1 and SORD proteins localized to uterine LE during the peri-implantation period, but expression switched to chorion by Day 20 and was maintained through Day 85. Uterine expression of AKR1B1 mRNA was down-regulated by estrogen. KHK protein localized to trophectoderm/chorion throughout gestation. These results provide evidence that components for the conversion of glucose to fructose and for fructose transport are present at the uterine-placental interface of pigs. The shift in expression from LE to chorion during pregnancy suggests free-floating conceptuses are supported by fructose synthesized by the uterus, but after implantation, the chorion becomes self-sufficient for fructose synthesis and transport.

Fructose-containing caloric sweeteners as a cause of obesity and metabolic disorders

“…In the placenta, the same pathway is responsible for the higher fructose concentration in the umbilical cord than in maternal blood. This has been observed mainly in ungulates (Steinhauser et al, 2016), but placental fructose synthesis has been well documented in humans too (Maragoudakis et al, 1984;Trindade et al, 2011). The functional significance of this observation remains unknown, although some authors propose that fructose may act as a growth factor during normal fetal development (Bazer et al, 2012;Wang et al, 2016).…”

Aldose Reductase B1 in Pig Seminal Plasma: Identification, Localization in Reproductive Tissues, and Relationship With Quality and Sperm Preservation

“…Aldose reductase B1 (AKR1B1 or ALR2), a NADPH-dependent enzyme that belongs to the aldo-keto reductase protein superfamily (Bohren et al, 1989;Hyndman et al, 2003), has been reported to play an essential role in both male and female reproductive systems in humans (Bresson et al, 2011), cattle (Frenette et al, 2004;Girouard et al, 2009), rats (Kobayashi et al, 2002), sheep (Yang et al, 2019), and pigs (Steinhauser et al, 2016;Pérez-Patiño et al, 2018). This enzyme is known to be involved in the polyol pathway for fructose production, specifically in the conversion of glucose into sorbitol (Kobayashi et al, 2002).…”

Functional amino acids in the development of the pig placenta

“…The porcine placenta lacks phosphate‐activated glutaminase. The enzymes catalyzing the indicated reactions are as follows: (1) enzymes for the degradation of amino acids in maternal tissues; (2) asparagine synthetase; (3) enzymes for the synthesis of purines and pyrimidines; (4) NADPH‐dependent aldose reductase and NAD + ‐dependent sorbitol dehydrogenase (Steinhauser et al, ); and (5) ATP‐dependent fructose kinase. KGM, α‐ketoglutaramate; OAA, oxaloacetate…”