Abstract: Objective To investigate the effect of heterozygous deletion of fibroblast growth factor receptor 1 (FGFR1) on reproductive function in congenital hypogonadotropic hypogonadism (CHH). Methods A heterozygous FGFR1 knockout mouse model (FGFR1^+/-) was established. Polymerase chain reaction (PCR) and Sanger sequencing were performed to confirm the deletion of the target exons. Immunohistochemistry and Western blot were used to detect FGFR1 protein expression. Reproductive capacity and function (including sperm concentration, motility, and progressive motility) were evaluated. Additionally, body mass index (BMI), testicular weight, testicular volume, and various sex hormone levels (including T, E2, AMH, FSH, LH, and INH-B) were measured and analyzed statistically. Results The FGFR1 heterozygous knockout mouse model was successfully constructed. PCR and sequencing results confirmed the deletion of exons 4 and 5 of the FGFR1 gene. Western blot and immunohistochemistry demonstrated reduced FGFR1 protein expression. Compared with wild-type (WT) mice, FGFR1^+/- mice exhibited significantly lower sperm motility(P＜0.001) and fewer progressively motile sperm (P＜0.01). Compared with WT mice, the INH-B level in FGFR1^+/- mice was slightly elevated (P＜0.05). Conclusions Heterozygous deletion of FGFR1 impairs sperm motility in mice, providing critical evidence for further elucidating the pathogenesis of reproductive dysfunction in congenital hypogonadotropic hypogonadism.

Key words: fibroblast growth factor receptor 1(FGFR1), spermatogenesis, testicular development, congenital hypogonadotropic hypogonadism (CHH)