The STK11 gene F354L mutation is associated with male spermatogenic dysfunction

Area of Science:

• Genetics
• Reproductive Biology
• Molecular Biology

Background:

• Male infertility affects a significant portion of the population.
• The STK11 gene plays a role in cellular functions relevant to reproduction.
• Specific mutations, like STK11 F354L, require investigation for their impact on male fertility.

Purpose of the Study:

• To determine the frequency of the STK11 F354L mutation in infertile males versus fertile controls.
• To elucidate the functional consequences of the STK11 F354L mutation on spermatogenesis and sperm function.

Main Methods:

• Polymerase Chain Reaction (PCR) and DNA sequencing were used to analyze the STK11 F354L coding sequence in patient and control groups.
• Immunofluorescence staining assessed STK11 expression and localization in testicular tissues and sperm.
• Lentivirus-mediated gene overexpression in TCAM2 cells, followed by Western blot and Golgi reorientation assays, evaluated the functional impact of the F354L variant.

Main Results:

• The STK11 F354L mutation was detected in both infertile patients (16 cases) and fertile controls (7 cases), with a statistically significant difference in mutation rates (p=0.043).
• STK11 protein is highly expressed in mouse testes and localized to the midpiece of human and mouse sperm.
• Overexpression of the F354L mutant STK11 in TCAM2 cells impaired AMPK phosphorylation and disrupted cellular polarity.

Conclusions:

• The STK11 F354L mutation is associated with male infertility and may impair spermatogenesis.
• The mutation's detrimental effects are linked to disruptions in metabolic homeostasis and cellular polarity.
• STK11 F354L represents a potential genetic factor contributing to male reproductive dysfunction.