Infertility observed in female rats treated with N-acetyl-L-cysteine: Histopathological examination of ovarian follicles and recovery of fertility.
We previously reported infertility in female rats that received N-acetyl-L-cysteine (NAC) intravenously at a dosage of 1000 mg/kg/day. Unfertilized oocytes and gestation day 1 and 2 embryos were assessed morphologically, and the results suggested that absence or thinning of the zona pellucida (ZP) is related to infertility. However, the morphological characteristics of oocytes before ovulation and recovery from the effects of NAC were not clarified. In the present study, the ovarian follicles were histopathologically examined and the recovery of reproductive function was evaluated to investigate the effects of NAC. Female Sprague-Dawley rats at 10 weeks of age received NAC intravenously at 1000 mg/kg/day for more than 1 week. Thinning of the ZP was observed in the ovarian follicles in all stages of growth by light microscopy. Outflow of the components of the ZP between the corona radiata and disarrangement of the corona radiata were more pronounced in growing follicles than in large secondary follicles. Similar findings were observed by electron microscopy, and the effects of NAC were limited to the ZP. Infertility and thinning of the ZP were observed in the no-recovery NAC group, but not in the recovery NAC group, in which animals recovered within four estrous cycles after NAC administration. It has been reported that the ZP is expressed by oocytes or by both oocytes and granulosa cells, but no changes were noted in these cells. The present findings suggest that NAC affects the ZP directly and that reproductive function may recover from the effects of NAC.
Harada
Miwa
M
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., 115 Tateiwa, Muya-cho, Naruto, Tokushima 772-8601, Japan. haradamw@otsukakj.co.jp
Kishimoto
Koji
K
Hagiwara
Rika
R
Nakashima
Yoshifumi
Y
Kurisu
Kazunobu
K
Kawaguchi
Yoshiro
Y
D000111:Acetylcysteine / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000633:toxicity*; D006107:Granulosa Cells / Q000187:drug effects; D007247:Infertility, Female / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D009865:Oocytes / Q000473:pathology* / Q000648:ultrastructure; D006080:Ovarian Follicle / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015044:Zona Pellucida / Q000187:drug effects* / Q000473:pathology
D016166:Free Radical Scavengers; D000111:Acetylcysteine