The STK11 gene F354L mutation is associated with male spermatogenic dysfunction

To investigate the probability of the STK11 gene F354L mutation in normal individuals and infertile males with spermatogenic dysfunction, and to predict its impact on male spermatogenic function. We analyzed the F354L coding sequence in 192 azoospermia and severe oligozoospermia patients (patient group) and 199 normal fertile males (control group) using PCR and DNA sequencing. We detected 16 cases of the mutation in the patient group, but 7 cases were also found in the control group. The mutation rate showed some significant statistical difference between the two groups (p = 0.043). Immunofluorescence staining revealed that STK11 is highly expressed in mouse testicular tissues and localized to the midpiece of human and mouse sperm. Lentivirus-mediated overexpression of wild-type and F354L-mutant STK11 in TCAM2 cells demonstrated that the F354L variant reduces AMPK phosphorylation and disrupts cellular polarity, as evidenced by Western blot and Golgi reorientation assays. These findings suggest that the F354L mutation may impair spermatogenesis and sperm motility by perturbing metabolic homeostasis and cell polarity.