cb 839 Due to its unusually long pre implantation period the

Due to its unusually long pre-implantation period [20,21], the horse conceptus is entirely dependent on histotrophic nutrition for the first 40 days of gestation [22]. During the pre-implantation period, glucose transporters in the endometrium and conceptus membranes must deliver the glucose required for embryonic development. To date, reports of glucose transporter expression during equine pregnancy have been limited to the description of SLC2A1 and SLC2A3 in the placental microcotyledons from day 100 of gestation [23]. As in other species, SLC2A1 was localized to the basolateral membrane of trophectoderm and endometrial epithelial cb 839 [2,8], whereas SLC2A3 was present at the apical microvillar junction (interdigitation of trophoblast and uterine epithelium [23,24]). We investigated the expression of glucose transporters (SLC2A1-2A5, SLC2A8, SLC2A10, SLC5A1 and SLC5A9-5A11) in equine conceptus membranes and endometrium during the oestrous cycle and early pregnancy. Previously, we abbreviated the period of endometrial progesterone-priming by transferring day 8 blastocysts (donor mare) into a 5-day negatively asynchronous (day 3) recipient mare. Asynchronous embryo transfer (ET) retarded conceptus development from at least as early as day 14 of pregnancy, and delayed upregulation of expression of various imprinted genes in conceptus membranes [25]. In the present study, we investigated whether delayed conceptus development following asynchronous ET was associated with altered glucose transporter expression.
Methods
Results SLC5A9 and SLC5A10 were not detected in endometrium or conceptus membranes.
Discussion Glucose is the main energy substrate for post-blastocyst embryo and placental development, and transporters are required to ensure sufficient glucose reaches the conceptus. The array of glucose transporters (facilitative and sodium-dependent) expressed in the endometrium and conceptus membranes during early pregnancy differs between species. Our study indicates that SLC2A1 and SLC2A3 are the most highly expressed glucose transporters in equine endometrium and conceptus membranes during early pregnancy. Moreover, asynchronous ET suggests that endometrial SLC2A1 upregulation depends on a combination of progesterone-priming and conceptus signalling. Surprisingly, SLC2A1 protein expression in the endometrium from pregnant mares appears to become less abundant from day 7 to day 28. In conceptus membranes, a wide range of glucose transporters was expressed during days 14–28; SLC2A1 protein was present in the apical part of trophectoderm cells and in endoderm.
Funding This work was supported by the European Commission, FP7-PEOPLE-2012-ITN [grant number 317146].
Conflicts of interest
Acknowledgments
Type 2 diabetes mellitus (T2DM) caused by lifestyle-related diseases is one of major global health problems leading to cardiovascular and/or neurodegenerative diseases. In fact, many R&D activities on T2DM has been increasing and a variety of antidiabetic drugs with new modes of action such as peroxisome proliferator-activated receptor γ(PPARγ) activators, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose transporter 2 (SGLT2) inhibitors, have been developed and used in clinical practice. However, in the later phase of disease any agents often failed to prevent use of injectable insulins, which are strongly effective drugs but have several demerits in the aspect of costs and usability. Therefore, we believe that further antidiabetic drugs with a novel mechanism of action are required. Insulin is the principal hormone regulating blood glucose homeostasis through several key actions, i.e. stimulation of glucose uptake and metabolism in the skeletal muscle, and adipose tissues, and inhibition of gluconeogenesis in the liver. Skeletal muscle is a major insulin’s target organ which is responsible for 80% of whole body insulin-stimulated glucose uptake, and its glucose uptake activity is decreased in T2DM patients. Appearance of inducible glucose transporter 4 (GLUT4) on the plasma membrane (GLUT4 translocation), account for insulin-stimulated glucose uptake activity in skeletal muscle through insulin receptor signaling mechanism. Therefore, we hypothesized that compounds stimulate GLUT4 translocation in the skeletal muscle would be a novel therapeutic agent.