title: CHFR is important for the survival of male premeiotic germ cells.
abstract: DNA damage response is required for male fertility. DNA damage repair mediates recombination between homologous chromosomes in meiotic prophase, which is essential for proper chromosome segregation during meiotic division. Interestingly, some DNA damage response proteins are also required for the survival of premeiotic germ cells, but their roles in these cells are still unclear. CHFR was recently shown to participate in DNA damage response, but it remains to be established if CHFR is required for male fertility. In this study, we characterized Chfr knockout male mice and found that around 30% of them were infertile. The onset of spermatogenesis was delayed and there was significant increase in apoptosis in premeiotic germ cells. This resulted in complete loss of germ cells in testes in 3 months and azoospermia in these mice. We further demonstrated that ATM activation was compromised in the testes of these mice. Therefore, CHFR is important for the survival of male premeiotic germ cells, which is likely through maintaining genomic stability in spermatogonial stem cells.
authors.affiliation: a Key Laboratory of Reproductive Genetics; Ministry of Education and Women's Reproductive Health Laboratory of Zhejiang Province; Women's Hospital; School of Medicine; Zhejiang University ; Hangzhou , Zhejiang , China.|b Institute of Translational Medicine; Zhejiang University ; Hangzhou , Zhejiang , China.
authors.forename: Lin-Yu
authors.initials: LY
authors.lastname: Lu
authors.affiliation: c Department of Cancer Genetics and Epigenetics ; Beckman Research Institute; City of Hope ; Duarte , CA USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D053713:Azoospermia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival; D004789:Enzyme Activation; D005298:Fertility; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability; D008297:Male; D008540:Meiosis; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D000075223:Poly-ADP-Ribose Binding Proteins; D015398:Signal Transduction; D013091:Spermatogenesis; D013094:Spermatozoa / Q000201:enzymology* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D025521:Tumor Suppressor Proteins; C558788:CHFR protein, mouse; D044767:Ubiquitin-Protein Ligases; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse
keywords: ATM activation; DNA damage repair; premeiotic germ cells