title: Sex dimorphism in late gestational sleep fragmentation and metabolic dysfunction in offspring mice.
abstract: BACKGROUND
  Excessive sleep fragmentation (SF) is common in pregnant women. Adult-onset metabolic disorders may begin during early development and exhibit substantial sex dimorphism. We hypothesized that metabolic dysfunction induced by gestational SF in male mice would not be apparent in female littermates.
  
  
  METHODS
  Body weight and food consumption were measured weekly in male and female offspring after late gestational SF or control sleep (SC). At 20 weeks, plasma leptin, adiponectin, lipid profiles, and insulin and glucose tolerance tests were assessed. Leptin and adiponectin, M1, and M2 macrophage messenger RNA expression and polarity were examined. Adiponectin gene promoter methylation levels in several tissues were assessed.
  
  
  RESULTS
  Food intake, body weight, visceral fat mass, and insulin resistance were higher, and adiponectin levels lower in male but not female offspring exposed to gestational SF. However, dyslipidemia was apparent in both male and female offspring exposed to SF, albeit of lesser magnitude. In visceral fat, leptin messenger RNA expression was selectively increased and adiponectin expression was decreased in male offspring exposed to gestational SF, but adiponectin was increased in exposed female offspring. Differences in adipokine expression also emerged in liver, subcutaneous fat, and muscle. Increased M1 macrophage markers were present in male offspring exposed to SF (SFOM) while increased M2 markers emerged in SF in female offspring (SFOF). Similarly, significant differences emerged in the methylation patterns of adiponectin promoter in SFOM and SFOF.
  
  
  CONCLUSIONS
  Gestational sleep fragmentation increases the susceptibility to obesity and metabolic syndrome in male but not in female offspring, most likely via epigenetic changes. Thus, sleep perturbations impose long-term detrimental effects to the fetus manifesting as sex dimorphic metabolic dysfunction in adulthood.
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: Abdelnaby
authors.initials: A
authors.lastname: Khalyfa
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: Alba
authors.initials: A
authors.lastname: Carreras
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: Isaac
authors.initials: I
authors.lastname: Almendros
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: Fahed
authors.initials: F
authors.lastname: Hakim
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, Biological Sciences Division, The University of Chicago, Chicago, IL.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000818:Animals; D001835:Body Weight; D019175:DNA Methylation; D004198:Disease Susceptibility; D004435:Eating; D044127:Epigenesis, Genetic; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012727:Sex Characteristics; D012890:Sleep / Q000235:genetics; D012892:Sleep Deprivation / Q000503:physiopathology*; D050151:Subcutaneous Fat / Q000378:metabolism
chemical_list: D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D008055:Lipids
keywords: adiponectin; epigenetic alterations; gestation; insulin resistance; metabolic syndrome; obesity; sexual dimorphism; sleep fragmentation