Sulfasalazine exposure during pregnancy and lactation: reproductive outcomes in male rat offspring

Abstract

Context Sulfasalazine (SAS) is a drug prescribed for pregnant and breastfeeding women with chronic inflammatory bowel diseases. SAS treatment induces transitory infertility in both adult men and male rats. Although SAS crosses the placenta and passes into maternal milk, the consequences of maternal SAS exposure on the reproductive development of male offspring needs further study. Aims The current study evaluated whether maternal SAS exposure interferes with the reproductive development of male rat offspring in the neonatal, infant, pubertal and adulthood periods. Methods Pregnant Wistar rats (n = 10/group) received 300 mg/kg/day of SAS dissolved in carboxymethyl cellulose (CMC), by gavage, from gestational day 0 to lactation day 21, and 3 mg/kg/day of folic acid during gestation. The control group received CMC. Key results During puberty, maternal SAS exposure increased the total length of seminiferous tubules, and round cells were observed in the lumen of caput and cauda epididymis. Moreover, SAS induced oxidative stress-related alterations in the testes of infant and adolescent rats. Conclusions Although maternal SAS treatment caused reproductive alterations in infant and adolescent male rats, in adulthood, there were no impairments in sperm parameters that could compromise fertility. Implications This study investigated the consequences of maternal exposure to SAS on the reproductive development of male rat offspring from birth to adulthood, employing a human-relevant dose. Thus, this study provides information for better understanding of SAS treatment during critical periods of development.