Puberty exposure to cigarette smoke extract impairs adult spermatogenesis in the mouse

Area of Science:

• Reproductive toxicology
• Environmental health
• Genetics

Background:

• Epidemiological studies link early-life environmental exposures to long-term health issues.
• Cigarette smoke is a known environmental toxin with potential reproductive consequences.

Purpose of the Study:

• To investigate the impact of early-life cigarette smoke extract (CSE) exposure on male reproductive health.
• To determine the role of the nuclear factor erythroid 2-related factor 2 (Nrf2) gene in mediating CSE's effects on spermatogenesis.

Main Methods:

• Utilized a nuclear factor erythroid 2-related factor 2 (Nrf2) knockout (KO) mouse model and wild-type (WT) littermates.
• Exposed mice to cigarette smoke extract (CSE) starting at 4 weeks of age.
• Assessed sperm concentration, motility, in vitro fertilization (IVF) rates, blastocyst rates, and antioxidant gene expression.

Main Results:

• CSE exposure significantly reduced sperm concentration and motility in 4-week-old Nrf2 KO mice compared to 8-week-old mice.
• CSE exposure decreased in vitro fertilization (IVF) and blastocyst rates in Nrf2 KO mice versus WT mice.
• Antioxidant gene expression was highest in CSE-treated WT mice at 8 weeks and lowest in CSE-treated KO mice at 4 weeks.

Conclusions:

• Pubertal exposure to CSE significantly impairs adult male spermatogenesis.
• The Nrf2 genotype plays a crucial role in the response to CSE exposure during development.
• Early-life CSE exposure poses a substantial risk to male reproductive function, modulated by antioxidant gene status.