Department of Animal Science, Texas A&M University, College Station, Texas, USA.
Department of Animal Science, Pennsylvania State University, University Park, Pennsylvania, USA.
Biol Reprod. 2024 Jul 12;111(1):148-158. doi: 10.1093/biolre/ioae043.
Fructose, the most abundant hexose sugar in fetal fluids and the blood of sheep and other ungulates and cetaceans, is synthesized from glucose via the polyol pathway in trophectoderm and chorion. However, the cell-specific and temporal expression of enzymes for the synthesis and metabolism of fructose in sheep conceptuses (embryo and placental membranes) and placentomes has not been characterized. This study characterized key enzymes involved in fructose synthesis and metabolism by ovine conceptuses throughout pregnancy. Day 17 conceptuses expressed mRNAs for the polyol pathway (SORD and AKR1B1) and glucose and fructose metabolism (HK1, HK2, G6PD, OGT, and FBP), but not those required for gluconeogenesis (G6Pase or PCK). Ovine placentomes also expressed mRNAs for SORD, AKR1B1, HK1, and OGT. Fructose can be metabolized via the ketohexokinase (KHK) pathway, and isoforms, KHK-A and KHK-C, were expressed in ovine conceptuses from Day 16 of pregnancy and placentomes during pregnancy in a cell-specific manner. The KHK-A protein was more abundant in the trophectoderm and cotyledons of placentomes, while KHK-C protein was more abundant in the endoderm of Day 16 conceptuses and the chorionic epithelium in placentomes. Expression of KHK mRNAs in placentomes was greatest at Day 30 of pregnancy (P < 0.05), but not different among days later in gestation. These results provide novel insights into the synthesis and metabolism of fructose via the uninhibited KHK pathway in ovine conceptuses to generate ATP via the tricarboxylic cycle, as well as substrates for the pentose cycle, hexosamine biosynthesis pathway, and one-carbon metabolism required for conceptus development throughout pregnancy.
果糖是胎液和绵羊及其他有蹄类和鲸目动物血液中含量最丰富的六碳糖，它可通过质膜糖酵解途径在滋养层和绒毛膜中由葡萄糖合成。然而，绵羊胚胎（胚胎和胎盘膜）和胎盘组织中果糖合成和代谢的关键酶的细胞特异性和时间表达尚未确定。本研究通过绵羊胚胎在整个妊娠期间的特征，确定了果糖合成和代谢中涉及的关键酶。妊娠第 17 天的胚胎表达了多元醇途径（SORD 和 AKR1B1）以及葡萄糖和果糖代谢（HK1、HK2、G6PD、OGT 和 FBP）的 mRNA，但不表达糖异生所需的（G6Pase 或 PCK）。绵羊胎盘组织也表达了 SORD、AKR1B1、HK1 和 OGT 的 mRNA。果糖可以通过酮己糖激酶（KHK）途径代谢，并且 KHK-A 和 KHK-C 同工酶在妊娠第 16 天的绵羊胚胎和妊娠期间的胎盘组织中以细胞特异性的方式表达。KHK-A 蛋白在胎盘组织的滋养层和胎盘中的子叶中更为丰富，而 KHK-C 蛋白在妊娠第 16 天的胚胎内胚层和胎盘组织的绒毛膜上皮中更为丰富。胎盘组织中 KHK mRNA 的表达在妊娠第 30 天最高（P<0.05），但在妊娠后期的不同天数之间没有差异。这些结果为绵羊胚胎通过未受抑制的 KHK 途径合成和代谢果糖提供了新的见解，以通过三羧酸循环生成 ATP，并为戊糖循环、己糖胺生物合成途径和整个妊娠期间胚胎发育所需的一碳代谢提供底物。
