Skip to main content
Anesthesia Progress logoLink to Anesthesia Progress
. 1990 Jul;37(4):176–180.

Nitrous oxide and infertility.

G Kugel 1, C Letelier 1, M A Zive 1, J C King 1
PMCID: PMC2148676  PMID: 2096739

Abstract

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.

Full text

PDF
180

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cohen E. N., Gift H. C., Brown B. W., Greenfield W., Wu M. L., Jones T. W., Whitcher C. E., Driscoll E. J., Brodsky J. B. Occupational disease in dentistry and chronic exposure to trace anesthetic gases. J Am Dent Assoc. 1980 Jul;101(1):21–31. doi: 10.14219/jada.archive.1980.0345. [DOI] [PubMed] [Google Scholar]
  2. Fink B. R., Shepard T. H., Blandau R. J. Teratogenic activity of nitrous oxide. Nature. 1967 Apr 8;214(5084):146–148. doi: 10.1038/214146a0. [DOI] [PubMed] [Google Scholar]
  3. Gillman M. A. Nitrous oxide, an opioid addictive agent. Review of the evidence. Am J Med. 1986 Jul;81(1):97–102. doi: 10.1016/0002-9343(86)90189-0. [DOI] [PubMed] [Google Scholar]
  4. Jones T. W., Greenfield W. Position paper of the ADA Ad Hoc Committee on trace anesthetics as a potential health hazard in dentistry. J Am Dent Assoc. 1977 Oct;95(4):751–756. doi: 10.14219/jada.archive.1977.0484. [DOI] [PubMed] [Google Scholar]
  5. King J. C., Lechan R. M., Kugel G., Anthony E. L. Acrolein: a fixative for immunocytochemical localization of peptides in the central nervous system. J Histochem Cytochem. 1983 Jan;31(1):62–68. doi: 10.1177/31.1.6187805. [DOI] [PubMed] [Google Scholar]
  6. Kugel G., Norris L. H., Zive M. A. Nitrous oxide and occupational exposure: it's time to stop laughing. Anesth Prog. 1989 Nov-Dec;36(6):252–257. [PMC free article] [PubMed] [Google Scholar]
  7. Mazze R. I., Wilson A. I., Rice S. A., Baden J. M. Reproduction and fetal development in rats exposed to nitrous oxide. Teratology. 1984 Oct;30(2):259–265. doi: 10.1002/tera.1420300213. [DOI] [PubMed] [Google Scholar]
  8. Middendorf P. J., Jacobs D. E., Smith K. A., Mastro D. M. Occupational exposure to nitrous oxide in dental operatories. Anesth Prog. 1986 Mar-Apr;33(2):91–97. [PMC free article] [PubMed] [Google Scholar]
  9. Ngai S. H., Finck A. D. Prolonged exposure to nitrous oxide decreased opiate receptor density in rat brainstem. Anesthesiology. 1982 Jul;57(1):26–30. doi: 10.1097/00000542-198207000-00008. [DOI] [PubMed] [Google Scholar]
  10. Novelli G. P., Casali R., De Gaudio A. R., Del Mese A., Falchi S., Festimanni F., Minoni C., Peduto V. A., Pieraccioli E., Piscitelli P. Il protossido d'azoto. Effetti neurologici, circolatori e cellulari. Minerva Anestesiol. 1981 Sep;47(9):565–644. [PubMed] [Google Scholar]
  11. Occupational disease among operating room personnel: a national study. Report of an Ad Hoc Committee on the Effect of Trace Anesthetics on the Health of Operating Room Personnel, American Society of Anesthesiologists. Anesthesiology. 1974 Oct;41(4):321–340. [PubMed] [Google Scholar]
  12. Vessey M. P., Nunn J. F. Occupational hazards of anesthesia. Br Med J. 1980 Sep 13;281(6242):696–698. doi: 10.1136/bmj.281.6242.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Vieira E., Cleaton-Jones P., Moyes D. Effects of intermittent 0.5% nitrous oxide/air (v/v) on the fertility of male rats and the post-natal growth of their offspring. Anaesthesia. 1983 Apr;38(4):319–323. doi: 10.1111/j.1365-2044.1983.tb10452.x. [DOI] [PubMed] [Google Scholar]
  14. Vieira E. Effect of the chronic administration of nitrous oxide 0.5% to gravid rats. Br J Anaesth. 1979 Apr;51(4):283–287. doi: 10.1093/bja/51.4.283. [DOI] [PubMed] [Google Scholar]

Articles from Anesthesia Progress are provided here courtesy of American Dental Society of Anesthesiology

RESOURCES