Nitrous oxide and infertility

Our laboratory has reported changes in luteinizing hormone releasing hormone (LHRH) from the hypothalamus following nitrous oxide (N2O) exposure. LHRH augments LH release, which in turn causes ovulation. This study evaluated how N2O disrupts ovulation and the possible resulting infertility. Adult virgin female rats (N = 64) were housed with a 12 h:12 h light cycle. Daily vaginal smears were taken and only rats exhibiting two consecutive normal 4-day ovulatory cycles were used. Thirty-two rats were placed in an environmental chamber and exposed to a mix of hydrated 30% N2O and compressed air delivered at 1.6 L/min for 8 h/day for 4 days (one cycle); controls received compressed air. All rats exposed to N2O exhibited disrupted cycles following the first day of the 4-day exposure. From a group of 12 N2O-exposed rats, 11 went into constant proestrus (day of ovulatory surge) for up to 3 weeks. Control rats cycled normally. Following each exposure, eight rats were perfused, brains sectioned, and LHRH cells identified by immunocytochemistry. Eight control rats also underwent this procedure. A threefold increase in LHRH cells was noted in N2O rats. In addition, 12 rats received 30% N2O for 4 days, followed by mating with proven male breeders for 4 days, as were controls. Six of 12 N2O rats and 12 of 12 control rats gave birth. Contrary to previous reports, no significant difference was noted in litter size or weight. The constant proestrus seen after N2O exposure is due to disruption of LHRH cells in the hypothalamus (blocked LHRH release). It is this disruption of LHRH, and therefore ovulation, which results in infertility.