Gene therapy with feline anti-Müllerian hormone analogs disrupts folliculogenesis and induces pregnancy loss in female domestic cats

William A. Stocker (), Lauren Olenick, Shreya Maskey, Denise Skrombolas, Haitong Luan, Sophie G. Harrison, Matt Wilson, Anne Traas, Mark Heffernan, Samantha Busfield, Kelly L. Walton and Craig A. Harrison ()
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William A. Stocker: Monash University
Lauren Olenick: 601 Walnut St
Shreya Maskey: Monash University
Denise Skrombolas: 601 Walnut St
Haitong Luan: Monash University
Sophie G. Harrison: Monash University
Matt Wilson: 601 Walnut St
Anne Traas: 601 Walnut St
Mark Heffernan: 601 Walnut St
Samantha Busfield: 601 Walnut St
Kelly L. Walton: The University of Queensland
Craig A. Harrison: Monash University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract For female domestic cats, ovariohysterectomy is the only method of inducing permanent infertility. However, hundreds-of-millions of free-roaming cats globally highlight the necessity for alternative contraceptive approaches. One strategy involves a single injection of vector delivering a fertility-inhibiting protein for lifetime contraception. Recent studies in mice and cats have identified anti-Müllerian hormone as an excellent candidate for this type of contraception. Here, we leverage our recent characterization of the molecular mechanisms underlying human anti-Müllerian hormone synthesis and activity, to generate potent feline anti-Müllerian hormone analogs. Single intramuscular delivery of these analogs to female cats using an adeno-associated viral vector leads to a greater than 1000-fold increase in feline anti-Müllerian hormone levels, which are sustained for 9 months. High serum anti-Müllerian hormone is associated with abnormal estrus cyclicity, non-follicular ovarian cyst formation, and a progressive decline in antral follicle numbers, however, the few surviving large follicles continue to ovulate. Unlike previous studies, supraphysiologic levels of anti-Müllerian hormone do not block conception, although they are incompatible with the maintenance of pregnancy. Our findings highlight the complexity of the effects of anti-Müllerian hormone on ovarian physiology but confirm that this growth factor is a candidate for fertility control in free-roaming cats.

Date: 2025
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DOI: 10.1038/s41467-025-56924-5

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