Infertility observed in female rats treated with N‐acetyl‐L‐cysteine: Histopathological examination of ovarian follicles and recovery of fertility

Abstract

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.

Follicular Fluid from Infertile Women with Mild Endometriosis Impairs In Vitro Bovine Embryo Development: Potential Role of Oxidative Stress

“…However, a study using a rat model demonstrated that intravenous NAC in high concentration (1000 mg.kg-1/day) promotes infertility probably due to an exacerbated thinning of the zona pellucida. 40 Thereby, further studies using animal models are needed to evaluate the effect of different concentrations of NAC to determine its efficacy and safety for embryos before its effects can be evaluated in infertile women with endometriosis.…”

Expression of genes encoding zona pellucida glycoproteins and cortical granule distribution in porcine oocytes isolated from small and medium follicles in relation to puberty status of donors

“…Presence of ZP2 (A) and ZP4 (B) transcripts was evaluated by RT-qPCR analysis MFCS = oocytes isolated from medium follicles of cycling sows, SFJG = oocytes from small follicles of juvenile gilts, SFCS = oocytes from small follicles of cycling sows Results are presented as mean ± SEM with the level of significance of P < 0.001 (*P < 0.01) a-c values with different superscripts are significantly different secondary sperm receptors, playing a significant role in gamete fusion during successful monospermic fertilization (Topfer-Petersen 1999). It has been previously shown in several species that oocytes lacking ZPs proteins are unable to fertilize (Harada et al 2003;Wassarman and Litscher 2012;Huang et al 2014). Ovarian follicle size significantly influences the ability of oocytes to mature and the gamete fertilizability.…”