Slc2a8 deficiency in mice results in reproductive and growth impairments.
SLC2A8, also known as GLUT8, is a facilitative glucose transporter expressed in the testis, brain, liver, heart, uterus, ovary, and fat. In this study we examined the effect of Slc2a8 deficiency on mouse gamete, preimplantation embryo, and implantation phenotype, as well as postnatal growth and physiology. For this model, the transcriptional start site and exons 1-4 were targeted and a lack of protein expression was confirmed by Western immunoblot. Oocytes obtained from Slc2a8(-/-) mice demonstrated abnormal metabolism and ATP production. In addition, deletion of Slc2a8 resulted in impaired decidualization, a critical step in the differentiation of endometrial stromal cells (ESCs), necessary for implantation. This indicates a role for SLC2A8 in decidualization, which is supported by Slc2a8 mRNA expression in both mouse and human ESCs, which increases dramatically in response to hormonal changes occurring during the process of implantation. Ovarian transplantation studies confirm that lack of SLC2A8 affects both the embryo and the implantation processes. This phenotype leads to decreased litter size, and smaller pups at weaning that continue to display an abnormally small growth phenotype into adulthood. The Slc2a8 null mice display decreased body fat by magnetic resonance imaging, and, interestingly, they are resistant to a diet high in fat and carbohydrates.
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
Katie L
KL
Adastra
Antonina I
AI
Frolova
Maggie M
MM
Chi
Daniel
D
Cusumano
Mary
M
Bade
Mary O
MO
Carayannopoulos
Kelle H
KH
Moley
D000818:Animals; D001835:Body Weight; D003656:Decidua / Q000502:physiology*; D059305:Diet, High-Fat; D010064:Embryo Implantation; D005260:Female; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000502:physiology*; D006706:Homeostasis; D008098:Litter Size; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism; D010053:Ovary / Q000033:anatomy & histology; D010641:Phenotype; D013081:Sperm Motility; D013737:Testis / Q000033:anatomy & histology; D014599:Uterus / Q000502:physiology
D051246:Glucose Transport Proteins, Facilitative; C498628:Slc2a8 protein, mouse; D005947:Glucose