ABSTRACT
Infertility in humans and subfertility in domestic animals are two major reproductive problems. Among human couples, ~15% are diagnosed as infertile, and males are considered responsible in about 50% of the cases. To examine male fertility, various sperm tests including analyses of sperm morphology, sperm count and sperm mobility are usually performed. Teratozoospermia, a condition characterized by the presence of morphologically abnormal sperm, is considered as a symptom of infertility. B10.MOL-TEN1 (TEN1) mice (Mus musculus) show inherited teratozoospermia at high frequencies (~50%). In this study, the polygenic control of teratozoospermia in the TEN1 strain was analysed. A quantitative trait loci analysis indicated three statistically significant loci, Sperm-head morphology 3 (Shm3; logarithm of the odds (LOD) score, 29.25), Shm4 (LOD score, 6.80), and Shm5 (LOD score, 3.58). These three QTL peaks were mapped to 24.3 centimorgans (cM) on chromosome 1, 32.0 cM on chromosome X, and 63.8 cM on chromosome 6, respectively. Another locus that is yet to be determined was also predicted. Shm3 was found to be the major locus responsible for teratozoospermia, and a sequential cascade of interactions of the other three loci was apparent. These results are expected to help understand the mechanisms underlying reproductive problems in humans or domestic animals.
Subject(s)
Epistasis, Genetic , Infertility, Male/genetics , Sperm Head/pathology , Alleles , Animals , Chromosome Mapping , Gene Expression Regulation , Genotyping Techniques , Infertility, Male/veterinary , Limit of Detection , Male , Mice , Models, Genetic , Quantitative Trait Loci , Sequence Analysis, DNAABSTRACT
Subfertility and infertility are two major reproductive health problems in human and domestic animals. The contribution of the genotype to these conditions is poorly understood. To examine the genetic basis of male subfertility, we analyzed its relationship to sperm morphology in B10.MOL-TEN1 mice, which shows high-frequencies (about 50%) of morphologically abnormal sperm. Drastic histological changes were also found in the testis of the B10.MOL-TEN1. Segregation analysis showed that the abnormal sperm phenotype in B10.MOL-TEN1 was inherited and was predictably controlled by at least three loci. We also found that male fertility of this strain was normal. These findings indicate a complicated relationship between sperm morphology and male subfertility.
Subject(s)
Fertility/genetics , Multifactorial Inheritance , Spermatozoa/metabolism , Spermatozoa/pathology , Animals , Chromosome Mapping , Female , Genetic Linkage , Male , Mice , Phenotype , Sperm Count , Sperm Head/pathology , Testis/metabolismABSTRACT
The B10.M mouse strain represents a model for male subfertility as it produces a significantly low number of offspring. The only known male reproductive phenotype of this strain is its high frequency of sperm-head morphological abnormalities (44.7 ± 2.4 %). We previously reported that this phenotype was the product of two recessive loci. In this study we mapped the loci causing the high frequency of sperm-head morphological abnormalities in this strain using F2 animals produced by crossing B10.M and C3H mice. Quantitative trait loci (QTL) analysis (n = 178) identified two recessive genes, one on Chromosome (Chr) 1 (LOD score = 30.585) and one on Chr 4 (LOD score = 4.532). Further analysis (n = 854) mapped the locus on Chr 1 between Ercc5 (23.55 cM) and D1Mit528 (25.95 cM) and the locus on Chr 4 between D4Mit148 (69.48 cM) and D4Mit170 (70.47 cM). It was also found that the effects of these two loci were not independent. The major locus on Chr 1 determines the expression of sperm-head abnormalities, while the locus on Chr 4 enhances the frequency of abnormalities only when the genotype of the Chr 1 locus is homozygous for the B10.M allele. The major locus on Chr 1 was named sperm-head morphology 1 (Shm1), while the modifier locus on Chr 4 was named sperm-head morphology 2 (Shm2).
