Multiple congenital malformations in a litter of feline fetuses associated with gestational exposure to a synthetic estrus-suppressing progestin

Abstract Background Congenital malformations in domestic cats are traditionally considered uncommon; however, recent evidence suggests they may represent an underrecognized cause of neonatal mortality. Most reported anomalies occur as isolated defects in individual animals, while the occurrence of multiple severe malformations within the same fetus or affecting an entire litter appears to be rare. Exposure to exogenous substances during critical windows of embryonic development has been proposed as a potential contributing factor. Reports describing congenital abnormalities in feline fetuses following gestational exposure to synthetic progestins remain scarce. Case presentation A three-year-old intact domestic shorthair cat was presented for veterinary evaluation due to dystocia approximately 65 days after repeated escape episodes from the household. In an attempt to suppress estrus and prevent mating, the owner administered two subcutaneous injections of a commercially available estrus-suppressing agent containing medroxyprogesterone acetate, before pregnancy was clinically recognized. Cesarean section revealed three dead fetuses, all presenting multiple congenital malformations. Cleft palate and arthrogryposis were observed in all fetuses, with arthrogryposis limited to the thoracic limbs in two and generalized in the third. Two female fetuses exhibited clitoromegaly consistent with virilization of the external genitalia. Additional findings included markedly reduced lung size suggestive of pulmonary hypoplasia in one fetus, cranium bifidum associated with meningocele in another, and severe axial and ventral body wall defects compatible with schistosomus retroflexus in the third. Rapid tests for feline immunodeficiency virus, feline leukemia virus, and feline panleukopenia virus in the queen were negative. Histopathological examination revealed diffuse vascular congestion and moderate autolysis, consistent with intrauterine fetal death, without evidence of inflammatory or infectious disease. Conclusions Although a direct causal relationship cannot be established, the temporal sequence of events and the spectrum of malformations observed are suggestive of disruption of early embryonic development. This case highlights the potential risks associated with the use of synthetic estrus-suppressing progestins in intact queens when pregnancy status is unknown. Increased awareness, cautious use of hormonal contraceptives, and further well-documented reports are warranted to better elucidate their potential impact on fetal development in cats.