Infertility Observed in Reproductive Toxicity Study of N-Acetyl-l-Cysteine in Rats

The toxic effects of i.v. administration of N-acetyl-l-cysteine (NAC), a component of parenteral nutrition solutions, on fertility and embryonic development were investigated in SD male and female rats at doses of 100, 300, and 1000 mg kg−1 day−1. Infertility was observed in females in the 1000-mg/k...

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Bibliographic Details
Published in:	Biology of reproduction Vol. 69; no. 1; pp. 242 - 247
Main Authors:	Harada, Miwa, Kishimoto, Koji, Furuhashi, Tadakazu, Naito, Kazuyosi, Nakashima, Yoshifumi, Kawaguchi, Yoshiro, Hiraoka, Isao
Format:	Journal Article
Language:	English
Published:	Madison, WI Society for the Study of Reproduction 01-07-2003
Subjects:	Acetylcysteine - administration & dosage Acetylcysteine - toxicity Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Biological and medical sciences Contents early development embryo Embryonic and Fetal Development - drug effects Emergency and intensive care: metabolism and nutrition disorders. Enteral and parenteral nutrition Female Infertility, Female - chemically induced Intensive care medicine Male Medical sciences Oocytes - drug effects Oocytes - pathology ovary ovum Pregnancy Rats Rats, Sprague-Dawley Reproduction - drug effects toxicology Zona Pellucida - drug effects Zona Pellucida - pathology Embryonic development Reproduction diseases Nutrition Rat Toxicity Thiohydroxyl group Rodentia Female sterility Germinal cell Route of administration Zona pellucida Parenteral administration Ovary Vertebrata Mammalia Aminoacid Animal Female genital system Oocyte
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Summary:	The toxic effects of i.v. administration of N-acetyl-l-cysteine (NAC), a component of parenteral nutrition solutions, on fertility and embryonic development were investigated in SD male and female rats at doses of 100, 300, and 1000 mg kg−1 day−1. Infertility was observed in females in the 1000-mg/kg group throughout the period from before mating to embryogenesis. No effect of NAC on the reproductive ability of the male rats was seen. The oocytes and embryos were assessed morphologically to clarify the cause of the effects of NAC. The unfertilized oocytes (UO) recovered from the ampullae of the uterine tubes and Gestational Day (GD) 1 and 2 embryos recovered from the oviducts or uterus of the rats that received NAC i.v. at a dosage of 1000 mg kg−1 day−1 for more than 1 wk before mating were assessed morphologically by stereomicroscopy. In addition, the thickness of the zona pellucida (ZP) was calculated by morphometric evaluation of the UO. Fewer UO were collected in the NAC group than in the control (nontreatment) group. Interestingly, ZP-lacking or partially ZP-lacking oocytes were observed in the NAC group, and the morphometric evaluation of the UO showed thinning of the ZP. The number of embryos in each animal was markedly decreased on GD1, and no embryos were recovered on GD2 in the NAC group. The oocytes that had ZP affected by NAC treatment were abnormal or nonviable. The findings of the present study suggest that changes in the ZP are related to the infertility associated with NAC.
ISSN:	0006-3363 1529-7268
DOI:	10.1095/biolreprod.102.013862