title: Parental diabetes: the Akita mouse as a model of the effects of maternal and paternal hyperglycemia in wildtype offspring.
abstract: OBJECTIVE
  Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyperglycemia in Akita mice). We determined metabolic and skeletal phenotypes in wildtype offspring of Akita mothers and fathers.
  
  
  RESULTS
  Both maternal and paternal diabetes resulted in phenotypic changes in wildtype offspring. Phenotypic changes were more pronounced in male offspring than in female offspring. Maternal hyperglycemia resulted in metabolic and skeletal phenotypes in male wildtype offspring. Decreased bodyweight and impaired glucose tolerance were observed as were reduced whole body bone mineral density and reduced trabecular bone mass. Phenotypic changes in offspring of diabetic fathers differed in effect size from changes in offspring of diabetic mothers. Male wildtype offspring developed a milder metabolic phenotype, but a more severe skeletal phenotype. Female wildtype offspring of diabetic fathers were least affected.
  
  
  CONCLUSIONS
  Both maternal and paternal diabetes led to the development of metabolic and skeletal changes in wildtype offspring, with a greater effect of maternal diabetes on metabolic parameters and of paternal diabetes on skeletal development. The observed changes are unlikely to derive from Mendelian inheritance, since the investigated offspring did not inherit the Akita mutation. While fetal programming may explain the phenotypic changes in offspring exposed to maternal diabetes in-utero, the mechanism underlying the effect of paternal diabetes on wildtype offspring is unclear.
authors.affiliation: Kinderklinik II, Division of Paediatric Endocrinology, UK- Essen and The University of Duisburg-Essen, Essen, Germany. corinna.grasemann@uk-essen.de
authors.forename: Corinna
authors.initials: C
authors.lastname: Grasemann
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Devlin
authors.forename: Paulina A
authors.initials: PA
authors.lastname: Rzeczkowska
authors.forename: Ralf
authors.initials: R
authors.lastname: Herrmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
authors.forename: Berthold P
authors.initials: BP
authors.lastname: Hauffa
authors.forename: Marc
authors.initials: M
authors.lastname: Grynpas
authors.forename: Christina
authors.initials: C
authors.lastname: Alm
authors.forename: Mary L
authors.initials: ML
authors.lastname: Bouxsein
authors.forename: Mark R
authors.initials: MR
authors.lastname: Palmert
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006943:Hyperglycemia / Q000175:diagnosis / Q000235:genetics*; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012727:Sex Characteristics
chemical_list: D007328:Insulin; D005947:Glucose