Stocker William A, Olenick Lauren, Maskey Shreya, Skrombolas Denise, Luan Haitong, Harrison Sophie G, Wilson Matt, Traas Anne, Heffernan Mark, Busfield Samantha, Walton Kelly L, Harrison Craig A
Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Scout Bio, 601 Walnut St, Philadelphia, PA, USA.
Nat Commun. 2025 Feb 15;16(1):1668. doi: 10.1038/s41467-025-56924-5.
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.
对于雌性家猫来说，卵巢子宫切除术是导致永久性不育的唯一方法。然而，全球数亿只散养猫凸显了采用替代避孕方法的必要性。一种策略是单次注射携带抑制生育蛋白的载体以实现终身避孕。最近在小鼠和猫身上的研究已确定抗苗勒管激素是这类避孕方法的极佳候选物。在此，我们利用近期对人类抗苗勒管激素合成及活性的分子机制的表征，来生成强效的猫抗苗勒管激素类似物。使用腺相关病毒载体将这些类似物单次肌肉注射到雌性猫体内，会使猫抗苗勒管激素水平提高1000倍以上，并持续9个月。高血清抗苗勒管激素与异常发情周期、非卵泡性卵巢囊肿形成以及窦卵泡数量逐渐减少有关，不过，少数存活的大卵泡仍会排卵。与之前的研究不同，超生理水平的抗苗勒管激素虽与维持妊娠不相容，但并不妨碍受孕。我们的研究结果凸显了抗苗勒管激素对卵巢生理影响的复杂性，但证实这种生长因子是散养猫生育控制的一个候选物。
