A Cascade of epistatic interactions regulating teratozoospermia
Received: 20 January 2015 / Accepted: 29 April 2015 / Published online: 12 May 2015
Ó Springer Science+Business Media New York 2015
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 ex-
amine male fertility, various sperm tests including analyses of
sperm morphology, sperm count and sperm mobility are
usually performed. Teratozoospermia, a condition character-
ized by the presence of morphologically abnormal sperm, is
considered as a symptom of infertility. B10.MOL-TEN1
(TEN1) mice (Mus musculus) show inherited teratozoosper-
mia 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 map-
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.
Reproduction is a highly regulated process that requires
coordination of the functions of numerous genes. Infertility
affects 10–15 % of human couples, and a male factor is es-
timated to be involved in nearly half of these cases (Visser
and Repping 2010). Among domestic animals, reproductive
performance has been declining for a long time in dairy cows
(Lucy 2001; Royal et al. 2008; Maas et al. 2009).
Approximately, 600 testis-speciﬁc 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). Informa-
tion regarding genetic abnormalities in spermatogenesis
obtained using reverse genetics approaches is expected to
further help understand male infertility. Recent advances in
genetics have paved the way for the development of ef-
fective methods to study male infertility and subfertility.
Accordingly, the number of ‘‘repro’’ mouse strains pro-
duced by the JAX Reproductive Mutagenesis Program
(Handel et al. 2006) has 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, reproduction is temporally regulated by the co-
ordinated action of a number of genes.
Electronic supplementary material The online version of this
article (doi:10.1007/s00335-015-9566-y) contains supplementary
material, which is available to authorized users.
& Hideo Gotoh
Animal Genome Research Unit, Agrogenomics Research
Center, National Institute of Agrobiological Sciences, 1-2
Owashi, Tsukuba, Ibaraki 305-8634, Japan
Graduate School of Science and Engineering, Yamagata
University, 1-4-12 Kojirakawa, Yamagata 990-8560, Japan
Technology and Development Team for Mouse Phenotype
Analysis, RIKEN BioResource Center, 3-1-1 Koyadai,
Tsukuba, Ibaraki 305-0074, Japan
Mamm Genome (2015) 26:248–256