VALPROATE AFFECTS THE MALE REPRODUCTIVE SYSTEM - A NEW EXPERIMENTAL MODEL
Abstract number :
2.336
Submission category :
Year :
2003
Submission ID :
3804
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Erik Ropstad, Anette Krogenaes, Ellen Dahl, Jan L. Lyche, Irma Oskam, Richard Wiger, Torres Sweeney, Audun Stien, Line Sveberg Roste, Erik Tauboll Department of Reproduction and Forensic Medicine, Norwegian School of Veterinary Science, Oslo, Norway; Nati
Long-term valproate (VPA) treatment induces changes in male reproductive endocrine function and testicular morphology in rats. Effects of VPA on sex steroid hormones and semen parameters have also recently been indicated in humans. The aim of the present study was to investigate the effects of VPA on the male reproductive system in a new chronic experimental animal model in mammals.
Nine bucks (+ 7 untreated controls), aged 2 months at start of the experiment, received VPA mixture in doses up to 62.5 mg/kg adjusted according to serum concentrations, given perorally twice daily for 8 months. Mean serum VPA concentration measured 2, 4 and 6 h after last dose was 694, 485 and 301 umol/l, respectively.Possible adverse effects in the reproductive system were investigated by assessing body weight, hormone levels (LH, FSH, testosterone), testicular image analysis, conventional sperm endpoints as well as flow cytometric analysis of testicular cell kinetics and sperm chromatin structure.
Semen volume and total sperm count was reduced by 15 and 19 %, respectively (P[lt]0.05). A significant increase was found for the percentage of sperm with abnormal chromatin as measured by the flow cytometric Sperm Chromatin Structure Assay (SCSA). No significant changes were found for the tubule epithelium image analysis, neither did quantitation of the different testis germ cell types by flow cytometric analysis detect any testicular cytotoxicity. Valproate exposure significantly decreased testicular diameter (8% compared with controls; P[lt]0.02). The prepubertal hormone concentrations of LH and testosterone were also significantly decreased leading to a delayed onset of puberty.
Long term VPA treatment had several adverse effects on the male reproductive system of adolescent goats including decreased testicular diameter, delayed onset of puberty and alterations in semen parameters. However in comparison with other studies, including human, the SCSA results after VPA treatment can still be categorized into the group with good fertility potential and do not necessarily indicate any biological adverse effects. Further studies are therefore needed to determine the biological significance of these findings.