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Dazl null mice cannot progress past meiotic prophase, with germ cell loss occurring
in the prenatal female and postnatal male. However, the specific function of Dazl
and exactly when the defect occurs during germ cell development in Dazl null mice
has yet to be fully elucidated; work is underway to determine the functional role of
Dazl in both in vivo and in vitro studies in mice (see Sect. 3.5 ).
In humans, all three DAZ family members are expressed in either fetal germ cells
and/or various stages of gamete development and maturation (Fig 3.2C ) (Reijo
et al. 2000 ; Xu et al. 2001 ; Dorfman et al. 1999 ). DAZL is expressed in prenatal
primordial germ cells and adult oocytes and follicles of the human female
(Figs. 3.2C and 3.3A a and b) (Dorfman et al. 1999 ; Brekhman et al. 2000 ;
Cauffman et al. 2005 ). DAZ and DAZL are expressed in prenatal germline stem
cells, and spermatogonia, spermatocytes, and spermatids of the adult man
(Figs. 3.2C and 3.3A e and f) (Reijo et al. 2000 ; Xu et al. 2001 ). BOULE is
expressed later in development in the cytoplasm of pachytene spermatocytes, per-
sists through meiosis, and decreases in early spermatids (Fig. 3.2C ) (Xu et al.
2001 ). Interestingly, DAZ and DAZL transit from the nucleus of spermatogonia to
the cytoplasm of spermatocytes during meiosis. Unlike DAZ , DAZL is further
expressed in developing spermatids and even mature spermatozoa (Fig. 3.2C )
(Reijo et al. 2000 ). It is likely that the DAZ genes have distinct, yet overlapping
spatio-temporal functions as RNA-binding proteins in the establishment of sper-
matogonial stem cell and oogonial populations and gametogenesis.
If a gene impacts the number of germ cells a person is born with or the total
gamete “pool” available, that gene should be expressed in the gametes and variable
in the human population. Interestingly, Tung et al. ( 2006b ) demonstrated that the
DAZL gene is variable and associated with the age of menopause, an indirect mea-
surement of the rate of oocyte/follicular depletion in women, as well as sperm
counts in men. Variation in the DAZL gene was analyzed by direct genetic sequenc-
ing in 93 women with Premature Ovarian Failure (POF; menopause before the age
of 40), 324 women with early (before age 46) or normal (after age 46) menopause,
and 102 infertile men ages 22-51. Ninety-five sequence variants of DAZL were
identified, most of which were single nucleotide polymorphisms or SNPs, where a
single nucleotide differs between members of a species and typically exists as one
of two alleles. Twelve of these DAZL SNPs were investigated for their association
with POF. Four of these common SNPs were significantly associated with the age
of menopause in the POF group, while six were significantly associated with total
sperm count and total motile sperm count among the infertile male group.
Haplotypes or combinations of associated SNPs of the DAZL gene were even more
strongly correlated with reproductive parameters in men and women. Several other
investigations on genetic variants of DAZL and reproductive parameters in men and
women have yielded contradictory findings, likely due to variation in study popula-
tion demographics, ethnic differences, sample sizes, and the polymorphisms ana-
lyzed among the studies (Becherini et al. 2004 ; Nuti and Krausz 2008 ; Teng et al.
2006 ; Thangaraj et al. 2006 ; Tschanter et al. 2004 ; Zerbetto et al. 2008 ).
The reported variants in the DAZL gene and their association with gamete para-
meters and infertility and/or age of ovarian failure further indicate a possible role
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