Male obesity is associated with subfertility and increased disease risk of offspring.It is unknown if effects can be reversed through pharmacological interventions.Five-to 6-week-old C57BL6 male mice were fed control ...Male obesity is associated with subfertility and increased disease risk of offspring.It is unknown if effects can be reversed through pharmacological interventions.Five-to 6-week-old C57BL6 male mice were fed control diet(n=10,CD)or high-fat diet(n=20,HFD)for 16 weeks.Animals fed with a HFD were then allocated to continuation of HFD(n=8)or HFD with metformin 28 mg kg1 day-1(n=8)for 6 weeks.Animals fed with CD continued on a CD(n=9).Males were mated with fertile C57BL6 females for the assessment of pregnancy and fetal growth.Sperm motility,spermatozoa and testicular morphology,sperm-zona pellucida binding,sperm reactive oxygen species(ROS)(intracellular[DCFDA],superoxide[MSR],and oxidative DNA lesions[8OHdG]),and mitochondrial membrane potential(JC1)were assessed.Metformin treatment of HFD males improved glucose toleranee(+12%,P<0.05)and reduced Homeostatic Model Assessment of Insulin Resistance(HOMA-IR;-36%,P<0.05).This occurred in the absenee of a change in body weight or adiposity.Metformin treatment of HFD-fed males restored testicular morphology(+33%,P<0.05),sperm motility(+66%,P<0.05),sperm-zona pellucida binding(+25%,P<0.05),sperm intracellular ROS concentrations(-32%,P<0.05),and oxidative DNA lesions(-45%,P<0.05)to the levels of the CD males.Metformin treatment of HFD fathers increased fetal weights and lengths compared with those born to HFD fathers(+8%,P<0.05),with fetal lengths restored to those of fetuses of CD males.Short-term metformin treatment in men who are obese could be a potential intervention for the treatment of subfertility,without the need for a reduction in body weight/adiposity.展开更多
Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage.Since sperm DNA damage may reduce embryo quality and increase miscarriage rates,it is possible that untreated sperm oxid...Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage.Since sperm DNA damage may reduce embryo quality and increase miscarriage rates,it is possible that untreated sperm oxidative stress may impair in vitro fertilization(IVF)live birth rates.Given that the antioxidant Menevit is reported to reduce sperm DNA damage,it was hypothesized that men’s consumption of this supplement may alter IVF outcomes.Therefore,a retrospective cohort study was conducted analyzing outcomes for couples undergoing their first fresh embryo transfer.Men were classified as controls if they were taking no supplements,health conscious controls if taking“general health”supplements,or Menevit users.Men with karyotype abnormalities,or cycles using donated,frozen and surgically extracted sperm were excluded.Among the final study cohort of 657 men,live birth rates were significantly higher in Menevit users than controls(multivariate adjusted odds ratio[OR]:1.57,95%confidence interval[Cl]:1.01-2.45,P=0.046),but not between controls taking no supplements and those using general health supplements,thereby suggesting that potential health conscious behavior in supplement users is unlikely responsible for the superior outcomes in Menevit users.Interestingly,in a post hoc sensitivity analysis,live birth rates among Menevit users were statistically superior to controls for lean men(OR:2.73,95%Cl:1.18-6.28;P=0.019),not their overweight/obese counterparts(OR:1.29,95%Cl:0.75-2.22,P=0.37).The results of this large cohort study therefore support a positive association between men’s use of the Menevit antioxidant during IVF treatment and live birth rates,especially in lean individuals.展开更多
文摘Male obesity is associated with subfertility and increased disease risk of offspring.It is unknown if effects can be reversed through pharmacological interventions.Five-to 6-week-old C57BL6 male mice were fed control diet(n=10,CD)or high-fat diet(n=20,HFD)for 16 weeks.Animals fed with a HFD were then allocated to continuation of HFD(n=8)or HFD with metformin 28 mg kg1 day-1(n=8)for 6 weeks.Animals fed with CD continued on a CD(n=9).Males were mated with fertile C57BL6 females for the assessment of pregnancy and fetal growth.Sperm motility,spermatozoa and testicular morphology,sperm-zona pellucida binding,sperm reactive oxygen species(ROS)(intracellular[DCFDA],superoxide[MSR],and oxidative DNA lesions[8OHdG]),and mitochondrial membrane potential(JC1)were assessed.Metformin treatment of HFD males improved glucose toleranee(+12%,P<0.05)and reduced Homeostatic Model Assessment of Insulin Resistance(HOMA-IR;-36%,P<0.05).This occurred in the absenee of a change in body weight or adiposity.Metformin treatment of HFD-fed males restored testicular morphology(+33%,P<0.05),sperm motility(+66%,P<0.05),sperm-zona pellucida binding(+25%,P<0.05),sperm intracellular ROS concentrations(-32%,P<0.05),and oxidative DNA lesions(-45%,P<0.05)to the levels of the CD males.Metformin treatment of HFD fathers increased fetal weights and lengths compared with those born to HFD fathers(+8%,P<0.05),with fetal lengths restored to those of fetuses of CD males.Short-term metformin treatment in men who are obese could be a potential intervention for the treatment of subfertility,without the need for a reduction in body weight/adiposity.
文摘Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage.Since sperm DNA damage may reduce embryo quality and increase miscarriage rates,it is possible that untreated sperm oxidative stress may impair in vitro fertilization(IVF)live birth rates.Given that the antioxidant Menevit is reported to reduce sperm DNA damage,it was hypothesized that men’s consumption of this supplement may alter IVF outcomes.Therefore,a retrospective cohort study was conducted analyzing outcomes for couples undergoing their first fresh embryo transfer.Men were classified as controls if they were taking no supplements,health conscious controls if taking“general health”supplements,or Menevit users.Men with karyotype abnormalities,or cycles using donated,frozen and surgically extracted sperm were excluded.Among the final study cohort of 657 men,live birth rates were significantly higher in Menevit users than controls(multivariate adjusted odds ratio[OR]:1.57,95%confidence interval[Cl]:1.01-2.45,P=0.046),but not between controls taking no supplements and those using general health supplements,thereby suggesting that potential health conscious behavior in supplement users is unlikely responsible for the superior outcomes in Menevit users.Interestingly,in a post hoc sensitivity analysis,live birth rates among Menevit users were statistically superior to controls for lean men(OR:2.73,95%Cl:1.18-6.28;P=0.019),not their overweight/obese counterparts(OR:1.29,95%Cl:0.75-2.22,P=0.37).The results of this large cohort study therefore support a positive association between men’s use of the Menevit antioxidant during IVF treatment and live birth rates,especially in lean individuals.
