Increasing use of ART to treat age-related infertility in men necessitates new therapeutic strategies to improve success rates. Chaperone-inducing drugs improve oocyte quality and embryo development in obese mice, but whether these improve sperm quality has not been investigated. The aim of this study was to determine whether treatment of sperm with a chaperone-inducing drug can improve gamete quality in older fathers.
Sperm from C57BL6 male mice that were either “old” (>14-months-old), or “young” (<8-months-old) was collected and treated in vitro during capacitation. Sperm quality assessments included motility, zona-binding capacity and mitochondrial activity. In parallel, sperm was used for IVF and embryo development was analyzed by time-lapse imaging.
Sperm from older males had reduced motility (N=9-12; P=0.03), lower mitochondrial membrane potential (N=6-11; P=0.04) and impaired zona-binding capacity (N=4-6; P=0.02) compared to younger males. Each of these sperm quality parameters was improved by treatment. When sperm was used for IVF, embryos from old males had delayed time to first cleavage (N=21-27; P=0.01). Sperm from older males gave decreased 2-cell (N=7-12; P=0.04) and blastocyst rates (N=7-12; P=0.003). Drug treatment of ‘old’ sperm restored embryo development rates to those of sperm from young males.
To test the efficacy of this in vitro treatment in humans, sperm samples from 40 ART patients were treated in vitro for 30 minutes. Sperm from older men (>40 years old) had reduced motility (N=14; P=0.03), as well as increased levels of both mitochondrial ROS (N=10; P<0.0001) and DNA oxidative damage after wash (N=15; P=0.004). Pharmaceutical treatment increased sperm motility by 10% in older men, while DNA damage levels were reduced in all patients (N=33; P=0.002; P=0.03).
These results demonstrate that male age negatively impacts sperm quality in both mice and humans. Further, pharmaceutical treatment in vitro normalizes sperm quality and, in mice, improves embryogenesis following IVF.