Making Germ Cells from Human Embryonic Stem Cells - Male Germline Stem Cells Developmental and Regenerative Potential - page 54

reproductive events including ovarian aging, the decline and eventual loss of fertility,
and menopause (Moore and Persaud 1998 ; Bancsi et al. 2002 ; de Boer et al. 2002 ;
Faddy et al. 1992 ; Hansen et al. 2008 ; Nichols et al. 2006 ; Richardson et al. 1987 ;
te Velde et al. 1998 ; Whelan et al. 1990 ). Despite recent work in mice suggesting
the existence of oogonial stem cells (Johnson et al. 2004, 2005 ), it is thought that
without this population of developmentally arrested oocytes the ovarian reserve
becomes depleted.
In contrast to that of the female, male germ cell development and spermatogen-
esis proceeds along quite a different course. The male PGCs form gonocytes, which
colonize the basement membrane of the seminiferous cords of the testes, which
later form the seminiferous tubules. The gonocytes differentiate into intermediate
spermatogonia and prespermatogonia, which are the precursors of the diploid sper-
matogonia of the adult (Gaskell et al. 2004 ). Similar to other mammals, the gono-
cytes and later, spermatogonia, remain connected by cytoplasmic bridges and are
enclosed within the supportive Sertoli cells lining the seminiferous tubules, isolating
the germ cells within their own compartment. The Sertoli cells are also in close
proximity to the interstitial hormone-secreting Leydig cells. Both the Sertoli cells
and spermatogonia are mitotically active during the pre-pubertal period in primates.
Notably, the spermatogonia do not enter meiosis during fetal development, but
rather await the endocrine signals of puberty to initiate spermatogenesis, proliferate
into clonal expansions of spermatogonia, undergo meiosis, become terminally
differentiated, and produce mature haploid spermatozoa capable of fertilization
(McLaren 2000 ; Yanagamachi 1994 ). Importantly, a reserve of spermatogonial
stem cells located at the periphery of the seminiferous tubules remains throughout
the male's entire life, allowing the continual production of sperm (Larsen 1997 ;
Yanagamachi 1994 ; Adams and McLaren 2002 ; McLaren and Southee 1997 ).
The development of sperm and their movement in the testis occurs progressively
from the periphery to the lumen of the tubules, and occurs in waves along the
tubules. In the final stage of spermatogenesis spermatids undergo the process of
spermiogenesis where they grow a tail or flagellum, develop an acrosomal vesicle,
condense and repackage their chromatin, and shed most of their cytoplasm. This
process gives rise to fully developed sperm that are shed from the lumen, leave the
testis, and enter the epididymis for final maturation and storage. Mature sperm are
highly polarized, terminally differentiated cells incapable of transcription and
protein synthesis. The specialized structural and cellular features of the spermatozoa
reflect its unique physiological role: to ensure the delivery of the male's genetic
material to the egg. The specialized sperm cell has the unique ability to find, fuse
with, and activate the egg. In the human, the entire process of spermatogenesis and
maturation takes approximately 77 days. A man in his reproductive prime produces
up to 240 million sperm per day, up to 450 million per ejaculate, and nearly 3,000
per heart beat [(Schuh 2007 ; Sutovsky and Manandhar 2006 ); J. Amory, personal
communication].
Although most sperm have the same basic morphology, including a head and
flagellum, and essential cellular components, there is variation in size and structure
between different species (Bedford and Cross 1998 ; Eddy and O'Brien 1994 ).