title: Aging sperm negatively impacts in vivo and in vitro reproduction: a longitudinal murine study.
abstract: OBJECTIVE
  To investigate the impact of paternal aging on reproductive success.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  Research facility.
  
  
  METHODS
  Outbred CF1 mice.
  
  
  METHODS
  Ten young male mice with proven fertility were mated routinely over 15 months with superovulated young females to assess in vivo and in vitro reproductive outcome.
  
  
  METHODS
  In vivo fertilization, in vivo fetal development, in vitro embryo morphology, and developmental outcome were assessed.
  
  
  RESULTS
  There were no differences observed for any reproductive end point until the paternal age of 12 months. At 12-15 months, in vivo fertilization was significantly decreased (35% vs. 78% at <12 months). Natural matings with males ≥ 12 months revealed significantly smaller fetuses (11.36 mm vs. 14.73 mm <12 months) and placental weight (0.10 g vs. 0.13 g at <12 months). In vitro blastocyst development showed a significant decline at ≥ 12 months, and in vitro blastocyst transfer resulted in a significant increase in pregnancy loss with males ≥ 12 months (61.5% vs. 0% at <12 months). In addition, the expression levels of Ace-1, Prm1, Prm2, and Smcp were observed to be decreased in sperm from males ≥ 12 months compared with young male control subjects.
  
  
  CONCLUSIONS
  Results from this study indicate an abrupt reproductive deterioration at paternal midlife, with an adverse effect observed on natural conception, in vitro blastocyst development, implantation potential, and fetal viability.
authors.affiliation: National Foundation for Fertility Research, Lone Tree, Colorado, USA. mkatz-jaffe@fertilityresearch.org
authors.forename: Mandy G
authors.initials: MG
authors.lastname: Katz-Jaffe
authors.forename: Jason
authors.initials: J
authors.lastname: Parks
authors.forename: Blair
authors.initials: B
authors.lastname: McCallie
authors.forename: William B
authors.initials: WB
authors.lastname: Schoolcraft
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005260:Female; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D011247:Pregnancy; D011897:Random Allocation; D012098:Reproduction / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology*