Sulfasalazine exposure during pregnancy and lactation: reproductive outcomes in male rat offspring
Simone Forcato
A , Ana Beatriz de Oliveira Aquino A , Lorena I. Borges A , Maria Luiza Francisconi Lubanco Thomé A , Júlia O. Bilibio A , Hannah Hamada Mendonça Lens B , Rafaela P. Erthal C , Flávia A. Guarnier B , Glaura Scantamburlo Alves Fernandes C and Daniela Cristina Ceccatto Gerardin A *
+ Author Affiliations
- Author Affiliations
A Department of Physiological Sciences, Londrina State University, Londrina, PR, Brazil.
B Department of General Pathology, Londrina State University, Londrina, PR, Brazil.
C Department of General Biology, Londrina State University, Londrina, PR, Brazil.
Reproduction, Fertility and Development 35(8) 469-479 https://doi.org/10.1071/RD22240
Published online: 21 April 2023
© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing
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.
Keywords: development, gestation, lactation, oxidative stress, pharmacology, reproduction, sperm, testis.
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