Gene therapy delivery of anti-Müllerian hormone in prepubertal female domestic cats induces long-term sterilization

Abstract

Abstract The uncontrolled reproduction of free-roaming domestic cats exacerbates their welfare challenges and the ecological pressure they exert on wildlife populations. Because of logistic and economic constraints, surgical sterilization alone cannot scale to control the reproduction of the hundreds of millions of intact cats worldwide. Herein, we report that the single administration of an adeno-associated viral vector delivering an anti-Müllerian hormone transgene to prepubertal cats can fully prevent pregnancy once females reach adulthood. Treated kittens were closely monitored for up to 21 months to assess long-term health, transgene expression, reproductive hormones, and reproductive function. The intramuscular injection was well tolerated and did not impact physical growth. The sustained expression of anti-Müllerian hormone did not impact spermatogenesis in males. However, it induced sterility in mated females by preventing breeding-induced ovulation and increases in progesterone associated with luteal phases, resulting in safe and potentially lifetime sterilization in the female domestic cat.