Triptolide induces adverse effect on reproductive parameters of female Sprague-Dawley rats.
The aim of this study was to investigate the adverse effects of triptolide, a diterpenoid triepoxid and a major active component isolated from Triptergium wilfordii Hook.f (TWHF), on various reproductive parameters of female Sprague-Dawley (SD) rats. Female SD rats were treated with triptolide by oral administration (gastric infusion; 0, 100, 200, and 400 μg/kg) once-daily for 90 days. During the experimental period, vaginal smears were taken to monitor the estrous phase for the last 30 days. Relative ovary and uterus weights to body and histopathologically changes were determined on the last day. Serum levels of estradiol (E(2)), progesterone (P), follicle-stimulating hormone (FSH), and luteotropic hormone (LH) were assessed by enzyme immunoassay. ERα expression in the uterus and ovaries were analyzed from using immunohistochemical detection. The results showed that treatment with 200 and 400 ug/kg of triptolide significantly reduced serum levels of E(2) and P and increased levels of FSH and LH. At these dose levels, relative weights of ovary and uterus were significantly reduced. Qualitative histological analysis of the ovaries revealed a reduction in developing follicles and increase in atretic follicles in treated animals. Further, estrous cycles were prolonged significantly. The expression of ERα in ovaries and the uterus decreased in treated animals. These data suggest that triptolide had a direct effect on the ovaries, and the decrease in steroids elicited feedback on FSH and LH. Thus, reduced levels of E(2) and P may affect follicular development, estrous cycle, and expression of ERα.
Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing, China.
Jing
J
Liu
Zhenzhou
Z
Jiang
Li
L
Liu
Yun
Y
Zhang
Shuang
S
Zhang
Jingwei
J
Xiao
Min
M
Ma
Luyong
L
Zhang
D000818:Animals; D004224:Diterpenes / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000009:adverse effects; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010616:Phenanthrenes / Q000009:adverse effects*; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D004224:Diterpenes; D004852:Epoxy Compounds; D047628:Estrogen Receptor alpha; D010616:Phenanthrenes; C001899:triptolide; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone