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

Philippe Godin, Nicholas Nagykery, Natalie Sicher, Julie L. Barnes, Amy G. Miller, Christina Bunner, Amy K. Thompson, Motohiro Kano, Guangping Gao, Dan Wang, Patricia K. Donahoe, Linda Rhodes, David A. Brake, Thomas J. Conlon, William F. Swanson, Lindsey M. Vansandt () and David Pépin ()
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Philippe Godin: Harvard Medical School, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery
Nicholas Nagykery: Harvard Medical School, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery
Natalie Sicher: Harvard Medical School, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery
Julie L. Barnes: Cincinnati Zoo and Botanical Garden, Center for Conservation and Research of Endangered Wildlife (CREW)
Amy G. Miller: Cincinnati Zoo and Botanical Garden, Center for Conservation and Research of Endangered Wildlife (CREW)
Christina Bunner: Cincinnati Zoo and Botanical Garden, Center for Conservation and Research of Endangered Wildlife (CREW)
Amy K. Thompson: Cincinnati Zoo and Botanical Garden, Center for Conservation and Research of Endangered Wildlife (CREW)
Motohiro Kano: Harvard Medical School, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery
Guangping Gao: University of Massachusetts Chan Medical School, Horae Gene Therapy Center
Dan Wang: University of Massachusetts Chan Medical School, Horae Gene Therapy Center
Patricia K. Donahoe: Harvard Medical School, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery
Linda Rhodes: Michelson Found Animals Foundation Inc.
David A. Brake: Michelson Found Animals Foundation Inc.
Thomas J. Conlon: Michelson Found Animals Foundation Inc.
William F. Swanson: Cincinnati Zoo and Botanical Garden, Center for Conservation and Research of Endangered Wildlife (CREW)
Lindsey M. Vansandt: Cincinnati Zoo and Botanical Garden, Center for Conservation and Research of Endangered Wildlife (CREW)
David Pépin: Harvard Medical School, Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Department of Surgery

Nature Communications, 2025, vol. 16, issue 1, 1-15

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.

Date: 2025
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DOI: 10.1038/s41467-025-65780-2

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