Polygenic expression of teratozoospermia and normal fertility in B10.MOL-TEN1 mouse strain

摘要

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. Reproduction is a highly regulated process that requires coordination of the functions of numerous genes. Infertility affects 10-15% of couples, and a male factor is estimated to be involved in nearly half of these cases (Visser and Repping 2010). Approximately 600 testisspecific protein-coding genes have been identified. Null mutations have been introduced in nearly 400 genes associated with spermatogenesis using knockout mouse technology (Matzuk and Lamb 2008; Jamsai and O’Bryan 2011; Massart et al. 2012). Information regarding genetic abnormalities in spermatogenesis derived using reverse genetics approaches is expected to help further understand male infertility. Recent advances in genetics have paved the way for the development of effective methods to study male infertility and subfertility. Accordingly, the number of “repro” mouse produced by JAX Reproductive Mutagenesis Program (Handel et al. 2006) reached more than a hundred, and a number of genes responsible for male infertility and subfertility have been identified (http:// reprogenomics.jax.org). The bidirectional approaches described above are intended to study infertility caused by a single gene. However, the reproduction is temporally regulated by coordinated action of a number of genes.