A new vaccine that targets two hormone receptors (FSHR and GnRH) was tested in female rats. It didn’t stop the rats from having normal cycles, but it made the fertile part of the cycle shorter, the non‑fertile part longer, and dramatically cut the number of pregnancies. The vaccine also made the ovaries and uterus smaller and changed the activity of genes involved in egg development.

The overpopulation of stray animals and wildlife may threaten human safety and health, while surgical contraception in female animals carries high costs and risks. Immuno-contraception serves as an effective solution to this challenge. This study developed a bivalent vaccine targeting both follicle-stimulating hormone receptor (FSHR) and gonadotropin-releasing hormone (GnRH), and validated in female rats. Results demonstrated that although the vaccine neither terminated estrous cycling nor altered its total duration, it significantly shortened follicular phases, prolonged luteal phases, reduced parturition rate (10 % vs. 100 % in experimental vs. control groups), and the ovarian/uterine weights of immunized rats during the diestrus phase were significantly lower than those of the control group. Ovarian histological analysis revealed that this vaccine suppressed the activation of primordial follicles and the maturation/ovulation of antral follicle, promoted follicular atresia. RT-qPCR analysis showed this vaccine downregulated the expression of follicle development-related genes (Bmp15, Cdh1, Erα and Wnt2), while upregulated expression of follicular atresia-related genes (Ar, Apc). These findings confirm the vaccine's significant contraceptive efficacy in female rats.