title: Valproate affects reproductive endocrine function, testis diameter and some semen variables in non-epileptic adolescent goat bucks.
abstract: Valproate (VPA) is a major antiepileptic drug with a broad spectrum of antiepileptic activity. There is, however, increasing concern about the possible effects of VPA on reproductive endocrine function. This study investigated the effects of valproate, on the endocrine and reproductive system of adolescent, non-epileptic, goat bucks. Nine goat bucks were orally treated with 62.5mg/kg valproate twice daily from 2 to 10 months of age in order to sustain therapeutic plasma concentrations of between 300 and 600 micromol/l. Seven bucks served as controls. Body weights and testicular diameters were recorded. Blood samples were collected for measurement of luteinising hormone (LH), follicle stimulating hormone (FSH) and testosterone three times weekly until sacrifice at approximately 40 weeks of age. Conventional reproductive endpoints were recorded and flow cytometric (FCM) analyses of spermatogenesis, including the sperm chromatin structure were conducted. Valproate-treated bucks had on average a higher body weight, but a lower testis diameter than controls. No significant differences were found for plasma FSH in comparison to controls. Valproate-treated bucks differed significantly from the control group by showing lower plasma concentrations of LH and testosterone and a later onset of puberty. A significantly higher proportion of sperm from valproate-treated bucks showed abnormal chromatin, demonstrating a harmful effect on DNA from valproate treatment. These results demonstrate that valproate was able to induce reproductive effects in goat bucks related to the hypothalamic-pituitary-axis, as well as to the testes.
authors.affiliation: Department of Production Animal Clinical Science, The Norwegian School of Veterinary Science, Oslo, Norway. anette.krogenaes@veths.no
authors.forename: A K
authors.initials: AK
authors.lastname: Krogenaes
authors.forename: E
authors.initials: E
authors.lastname: Taubøll
authors.forename: A
authors.initials: A
authors.lastname: Stien
authors.forename: I C
authors.initials: IC
authors.lastname: Oskam
authors.forename: J L
authors.initials: JL
authors.lastname: Lyche
authors.forename: E
authors.initials: E
authors.lastname: Dahl
authors.forename: R F
authors.initials: RF
authors.lastname: Thomassen
authors.forename: T
authors.initials: T
authors.lastname: Sweeney
authors.forename: E
authors.initials: E
authors.lastname: Ropstad
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004703:Endocrine System / Q000187:drug effects*; D004827:Epilepsy / Q000188:drug therapy / Q000662:veterinary; D005434:Flow Cytometry; D015511:Goat Diseases / Q000188:drug therapy; D006041:Goats / Q000502:physiology*; D006728:Hormones / Q000097:blood; D008297:Male; D012661:Semen / Q000187:drug effects*; D012670:Seminiferous Epithelium / Q000187:drug effects; D013737:Testis / Q000187:drug effects*; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D006728:Hormones; D014635:Valproic Acid