Role of N-acetylcysteine in animal reproduction: a comprehensive review

Abstract

N-acetylcysteine (NAC), a thiol-containing acetylated derivative of L-cysteine, has emerged as a biologically versatile compound with substantial relevance to animal reproductive physiology. Its principal mechanism of action is replenishment of intracellular glutathione through cysteine donation; secondary actions include direct scavenging of reactive oxygen species, modulation of redox-sensitive signalling pathways, hydrogen sulfide generation, metal chelation, and disruption of mucin disulfide bonds. Oxidative stress is a central disruptor of gamete quality, fertilization, implantation and early embryonic development across species. In vitro and in vivo evidence from cattle, sheep, goats, horses, dogs, buffaloes, and laboratory animals consistently demonstrates that NAC improves oocyte maturation and developmental competence, protects granulosa cells from apoptosis via PI3K/AKT signalling, supports early pregnancy establishment, attenuates endometrial inflammation and improves clinical fertility outcomes in mares with endometritis. NAC also preserves sperm motility, viability and mitochondrial function during semen extension and cryopreservation, and exhibits direct antibacterial and antiinflammatory activity relevant to mastitis-associated infertility in dairy cattle. These findings collectively established NAC as a promising antioxidant strategy for improving fertility and reproductive efficiency in domestic animals. This review consolidates current mechanistic and applied evidence on NAC in animal reproduction and identifies priority areas for future research.