Effects of carbamazepine-exposure on rat epididymal sperm in parental (F0) and F1 generations.

Carbamazepine (CBZ) is a medication used for neurological and psychiatric disorders treatment. Its potential side effects on male reproduction are a cause for concern. Alterations in sperm parameters and sex hormone levels have been reported during and after prolonged therapy with CBZ. However, alterations in sperm quality are not necessarily associated with a decrease in fertility, and may potentially lead to adverse effects on the offspring. The study aimed to evaluate the qualitative and quantitative parameters of epididymal sperm in CBZ-treated adult rats from pre-puberty to adulthood (F0 generation) and their potential impact on the spermatozoa of their offspring (F1 generation). Male rats were treated with CBZ (20 mg/Kg/day), administered by gavage, from pre-puberty (23 postnatal days - pnd) until adulthood (95pnd). The control group received olive oil (vehicle) following the same experimental procedure. At 95pnd, sperm qualitative and quantitative parameters were analyzed in the F0 and F1 generations. Measurements of testicular and epididymal malondialdehyde levels and plasma testosterone levels were also performed. Paternal chronic CBZ exposure (F0 generation) reduced sperm motility and viability, increased DNA fragmentation, and altered mitochondrial activity and acrosome integrity. Testosterone levels, testicular step 19 spermatid and daily sperm production also decreased. Significant increases in oxidative stress in the testis and epididymis were observed. These alterations also occurred in the F1 generation. The results suggest that prolonged paternal exposure to CBZ can cause sperm qualitative and quantitative alterations, decrease in testosterone levels, affecting intergenerationally the male reproductive health of offspring.