Prepubertal treatment of rats with clomiphene citrate affects postpubertal testicular development

Abstract

A previous study showed that clomiphene citrate (clomiphene) reduced serum and pituitary gonadotropins and impaired testis growth and steroidogenesis in 10-day-old rats treated for up to two weeks. The present study was conducted to assess the effect of prepubertal clomiphene treatment on postpubertal pituitary-testicular function. Rats were implanted with pellets that released 0, 0.05, 0.5 or 5.0 mg clomiphene.kg-1.day-1 between 10-31 days of age and were killed at 90 days of age. Testis and prostate weights in treated rats were reduced (P less than 0.05), whereas serum LH, FSH and testosterone, and pituitary gonadotropin and GnRH receptor concentrations had recovered to levels observed in control rats. Testicular FSH receptor concentrations were not altered; however, FSH receptor content was decreased (P less than 0.05) in clomiphene-treated rats proportional to the reduction in testicular weight. In contrast, testicular LH and GnRH receptor concentrations were increased (P less than 0.05) in treated animals, resulting in similar receptor contents. Daily sperm production per gram of parenchyma was unaffected, while daily sperm production per testis was decreased in treated rats (P less than 0.05). These data show early postnatal treatment with clomiphene does not permanently impair pituitary function. Despite reduced testicular mass, normal serum testosterone concentrations and testis LH receptor content of treated rats suggest recovered Leydig cell function. The decreased content of testicular FSH receptors and reduced sperm production suggest seminiferous tubule function was compromised in the adult rat.