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

Abstract

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.

Retinoic acid stimulation of VEGF secretion from human endometrial stromal cells is mediated by production of reactive oxygen species

“…We now show that the effects of RA on VEGF production are, at least partly, mediated through a tightly regulated increase in ROS production in endometrial stromal cells. Other evidence for this mechanism of RA regulation of VEGF in early angiogenic events of pregnancy comes from in vivo studies demonstrating reduced fecundity of rats treated with NAC (Harada et al 2003). Findings of this work included a significant increase in post‐implantation pregnancy loss in NAC‐treated rats whose blood levels can be calculated to approximate the NAC concentrations used in our in vitro assays to block RA stimulation of VEGF secretion (250 m m ).…”

The Potential Use of Metformin, Dipyridamole, N-Acetylcysteine and Statins as Adjunctive Therapy for Systemic Lupus Erythematosus

“…It is potentially therapeutic for diseases in which the impact of free oxygen radicals on the disease pathophysiology is substantial [43]. This includes treatment for acetaminophen toxicity [44], chronic bronchitis [42] and obstetric and gynaecological conditions such as polycystic ovary syndrome [45] and premature birth [43].…”

Differential Testicular Gene Expression in Seasonal Fertility

“…Many of these have been discovered by phenotypic analysis of transgenic and knockout mice. It is highly likely that many more such fertility loci remain to be discovered, not only by further targeted approaches but also by analysis of spontaneous mutants (Cha et al 2004; Clark et al 2004; Harada et al 2003; Lalouette et al 1996; Meng et al 2002; Rule et al 1999) and by focussed chemical mutagenesis screens (Lessard et al 2004). The uncharacterised ESTs exhibiting differential expression identified in this study may thus be candidates for the genes underlying uncharacterised fertility loci associated with defects in spermatogenesis.…”