Adenine nucleotide translocase 4 deficiency leads to early meiotic arrest of murine male germ cells.
Male fertility relies on the highly specialized process of spermatogenesis to continually renew the supply of spermatozoa necessary for reproduction. Central to this unique process is meiosis that is responsible for the production of haploid spermatozoa as well as for generating genetic diversity. During meiosis I, there is a dramatic increase in the number of mitochondria present within the developing spermatocytes, suggesting an increased necessity for ATP production and utilization. Essential for the utilization of ATP is the translocation of ADP and ATP across the inner mitochondrial membrane, which is mediated by the adenine nucleotide translocases (Ant). We recently identified and characterized a novel testis specific Ant, ANT4 (also known as SLC25A31 and Aac4). The generation of Ant4-deficient animals resulted in the severe disruption of the seminiferous epithelium with an apparent spermatocytic arrest of the germ cell population. In the present study utilizing a chromosomal spread technique, we determined that Ant4-deficiency results in an accumulation of leptotene spermatocytes, a decrease in pachytene spermatocytes, and an absence of diplotene spermatocytes, indicating early meiotic arrest. Furthermore, the chromosomes of Ant4-deficient pachytene spermatocyte occasionally demonstrated sustained gammaH2AX association as well as synaptonemal complex protein 1 (SYCP1)/SYCP3 dissociation beyond the sex body. Large ATP supplies from mitochondria may be critical for normal progression of spermatogenesis during early stages of meiotic prophase I, including DNA double-strand break repair and chromosomal synapsis.
Brower
Jeffrey V
JV
Departments of Pathology Physiology, University of Florida College of Medicine, PO Box 100275, Gainesville, Florida 32610, USA.
Lim
Chae Ho
CH
Jorgensen
Marda
M
Oh
S Paul
SP
Terada
Naohiro
N
D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005260:Female; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006657:Histones / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D049471:Pachytene Stage / Q000235:genetics / Q000502:physiology; D013090:Spermatocytes / Q000378:metabolism / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D013997:Time Factors
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; C490062:Sycp3 protein, mouse; C524039:adenine nucleotide translocase 4, mouse; C475961:gamma-H2AX protein, mouse