Making Germ Cells from Human Embryonic Stem Cells - Male Germline Stem Cells Developmental and Regenerative Potential - page 55

Generally, sperm range from ~30 to 250 mm long, depending on the species
(Baccetti and Afzelius 1976 ). However, there are striking exceptions, including the
giant 6-cm-long sperm of the tiny fruit fly Drosophila bifurca (Pitnick et al. 1995 )
and the tail-less ameboid sperm of the round worm Caenorhabditis elegans
(Kubagawa et al. 2006 ). One interesting paradox is that some of the smallest
animals have some of the largest sperm, and the largest animals have some of
the smallest sperm (whales with ~30−60 mm long sperm). These differences may
be due to evolutionary pressures shaped by mating behavior, occurrence of inter-
male sperm competition, and the shape and size of the female reproductive tract
(Schuh 2007 ; Bjork and Pitnick 2006 ; Parker et al. 1972 ; Shuster and Wade 2003 ).
While there are great size differences, mammals show less variation in sperm
structure than other animals. Although sperm are uniform in size and shape within
most species, there is some variability in sperm morphology, especially the head, in
human sperm (Eddy and O'Brien 1994 ). There is also great variation in the num-
bers of sperm that are produced both between species and among members of the
same species. Notably, there is variability in the quantity of sperm produced by
different men and by the same man over time. The reference values for normal
sperm parameters of seminal fluid are >50% motile sperm, >20 million sperm per
ml, and >40% normal morphology (WHO 1999 ). Decreases in any of these can
synergistically decrease male fertility. A main cause of infertility in men is the
production of reduced numbers of sperm, and sperm with defects in motility
[J. Amory, personal communication; (Guzick et al. 2001 ; Turner 2003 )]. It is esti-
mated that about 75% of infertile men are either oligospermic (have few sperm; <20
million per ml) or have a high percentage of immotile sperm (asthenozoospermia)
(Baker et al. 1986 ).

3.2.3 The Molecular Requirements of Germ Cell Development

Although we have an increasing understanding of the morphological sequences of
human germ cell, and subsequent sperm and egg development in vivo , we have yet
to elucidate the many genes, proteins, and molecular events that underlie this
important process. We also have gained some insight about many of the genes and
signaling pathways that function in mature human gametes. However, despite its
importance to understanding reproductive health and fertility, what little we know
about the genetics and molecular events of early human germ cells has been mostly
extrapolated from studies in mice. It is likely that human germ cells are specified
and formed through the action of sequentially expressed genes similar to that of
mice and other model organisms. Thus, the generation of knockout and transgenic
mice has been integral in elucidating some of the key genetic pathways of early
germ cell development.
In mice, with a total gestation of roughly 20 days, specification of PGCs occurs
relatively late in embryonic development. After implantation of the blastocyst,
which occurs on embryonic day 5 (E5), the PGCs arise around E7.2 by inductive