Paternal effect on embryo quality in diabetic mice is related to poor sperm quality and associated with decreased glucose transporter expression.
The objective of this study was to determine whether sperm quality, fertilization capacity, and subsequent embryo development are altered in diabetic male mice and whether differences in facilitative glucose transporter (GLUT; now known as solute carrier family 2, SLC2A) expression in the testis and sperm exist. Using two type 1 diabetic mouse models, SLC2A expression in the testis and sperm was determined by western immunoblotting and immunofluorescence staining. To address sperm quality and fertilization capacity, computer-assisted sperm analysis and in vitro fertilization were performed. SLC2A1, SLC2A3, and SLC2A5 did not change in expression in the testes or sperm between diabetic and non-diabetic mice. SLC2A8 and SLC2A9b were less expressed in the testes of both diabetic models versus controls. SLC2A9a was not expressed in the Akita testis or sperm when compared with strain-matched controls. 3beta-hydroxysteroid dehydrogenase (HSD3B) expression was significantly decreased in the Leydig cells from the diabetic mice. Sperm concentration and motility were significantly lower in both the diabetics when compared with the control. These parameters normalized in Akita diabetic males treated with insulin. In addition, fertilization rates were significantly lower in the Akita group (17.9%) and the streptozotocin (STZ)-injected male group (43.6%) when compared with the normal group (88.8%). Interestingly, of the fertilized zygotes, embryo developmental rates to the blastocyst stage were lower in both diabetic models (7.1% Akita and 50.0% STZ) when compared with controls (71.7%). Male diabetes may cause male subfertility by altering steroidogenesis, sperm motility, and SLC2A expression. This is the first study to link a paternal metabolic abnormality to a sperm effect on cell division and subsequent embryonic development.
Department of Obstetrics and Gynecology, Washington University in St Louis, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
Sung Tae
ST
Kim
Kelle H
KH
Moley
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D047108:Embryonic Development / Q000502:physiology; D005260:Female; D005307:Fertilization in Vitro; D005455:Fluorescent Antibody Technique; D051246:Glucose Transport Proteins, Facilitative / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007248:Infertility, Male / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000032:analysis / Q000627:therapeutic use; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D023421:Models, Animal; D013076:Sperm Count; D013081:Sperm Motility; D013094:Spermatozoa / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000378:metabolism
D051246:Glucose Transport Proteins, Facilitative; D007328:Insulin