Male infertility has been shown to be associated with a defective annulus, a ring structure that demarcates the midpiece and the principal piece of the sperm tail. The firm attachment of the annulus to the flagellar membrane suggests ... Male infertility has been shown to be associated with a defective annulus, a ring structure that demarcates the midpiece and the principal piece of the sperm tail. The firm attachment of the annulus to the flagellar membrane suggests that it may supply mechanical support and prevent displacement of the caudal mitochondrial helix (summary by Kuo et al., 2012).
Kuo et al. (2012) studied 2 infertile men with SEPT12 mutations. The first man had asthenoteratozoospermia, with a sperm count of 20.5 x 10(6)/ml, morphology that was 92% abnormal, and a total motility of 48% (42% rapid progressive ... Kuo et al. (2012) studied 2 infertile men with SEPT12 mutations. The first man had asthenoteratozoospermia, with a sperm count of 20.5 x 10(6)/ml, morphology that was 92% abnormal, and a total motility of 48% (42% rapid progressive motility, 6% slow progressive motility, and 52% nonprogressive motility). The second man had oligoasthenozoospermia, with a sperm count of 0.9 x 10(6)/ml, morphology that was 80% abnormal, and a total motility of 22% (consisting of 22% slow progressive motility and 78% nonprogressive motility; no rapid progressive motility was seen in this patient's sperm). Atomic force microscopy of the second man's sperm detected loss of the annular structure and a bent tail, as well as outward exposure of the flagellar axoneme. The height of the annulus site was about 20 to 40 nm, significantly lower than in a control (160 nm). Under bright-field and fluorescence microscopy, the sperm had multiple defects; transmission electron microscopy showed noncondensed chromatin material, cytoplasmic droplets, a shrunken joining point with minimal connection, and a bent tail.
Lin et al. (2012) analyzed the SEPT12 gene (611562) in 160 infertile men and 200 fertile controls and identified a variant (474G-A; 611562.0001) that was more prevalent in infertile men than controls, in both allele (p = 0.007) ... Lin et al. (2012) analyzed the SEPT12 gene (611562) in 160 infertile men and 200 fertile controls and identified a variant (474G-A; 611562.0001) that was more prevalent in infertile men than controls, in both allele (p = 0.007) and genotype (p = 0.003) frequencies. Of 15 infertile men who were homozygous for the SNP (474A/A), 9 had teratozoospermia (88 to 99% of abnormal sperm). Motile sperm organelle morphology examination and immunofluorescence assay showed that most sperm had distinct pathologic features, including a bent tail, head with abnormal shape, and immature spermatid. Transfection studies showed that the mutant SEPT12 disrupted filament formation of wildtype SEPT12 in a dose-dependent manner. Examination of sperm from 474A/A infertile men by transmission electron microscropy showed a loose nuclear matrix; narrow head and decondensed nuclear matrix was observed under atomic force microscopy. Kuo et al. (2012) analyzed the SEPT12 gene in 160 infertile men and identified 2 heterozygous missense mutations, 1 in a man with asthenoteratozoospermia and 1 in a man with oligoasthenozoospermia (611562.0002, 611562.0003). Functional analysis demonstrated that both mutations adversely affected filament formation of wildtype SEPT12 in a dose-dependent manner.