Aging sperm negatively impacts in vivo and in vitro reproduction: a longitudinal murine study

Abstract

To investigate the impact of paternal aging on reproductive success. Animal study. Research facility. Outbred CF1 mice. 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. In vivo fertilization, in vivo fetal development, in vitro embryo morphology, and developmental outcome were assessed. 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. 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.