title: Knockout of BRD7 results in impaired spermatogenesis and male infertility.
abstract: BRD7 was originally identified as a novel bromodomain gene and a potential transcriptional factor. BRD7 was found to be extensively expressed in multiple mouse tissues but was highly expressed in the testis. Furthermore, BRD7 was located in germ cells during multiple stages of spermatogenesis, ranging from the pachytene to the round spermatid stage. Homozygous knockout of BRD7 (BRD7(-/-)) resulted in complete male infertility and spermatogenesis defects, including deformed acrosomal formation, degenerative elongating spermatids and irregular head morphology in postmeiotic germ cells in the seminiferous epithelium, which led to the complete arrest of spermatogenesis at step 13. Moreover, a high ratio of apoptosis was determined by TUNEL analysis, which was supported by high levels of the apoptosis markers annexin V and p53 in knockout testes. Increased expression of the DNA damage maker λH2AX was also found in BRD7(-/-) mice, whereas DNA damage repair genes were down-regulated. Furthermore, no or lower expression of BRD7 was detected in the testes of azoospermia patients exhibiting spermatogenesis arrest than that in control group. These data demonstrate that BRD7 is involved in male infertility and spermatogenesis in mice, and BRD7 defect might be associated with the occurrence and development of human azoospermia.
authors.affiliation: Hunan Cancer Hospital and The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China.|Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Heran
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Chi
authors.initials: C
authors.lastname: Guo
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Shihe
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of reproduction and stem cell engineering, Central South University, Changsha, Hunan, 410078, P.R. China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Fan
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Peng
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The Third Xiang-Ya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama 36604, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Schmitt
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama 36604, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.affiliation: Hunan Cancer Hospital and The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China.|Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: Hunan Cancer Hospital and The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China.|Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan, 410078, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency*; D045643:DNA Repair Enzymes / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D007248:Infertility, Male; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013091:Spermatogenesis; D013737:Testis / Q000473:pathology; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D045643:DNA Repair Enzymes; C400206:Brd7 protein, mouse; D000092468:Bromodomain Containing Proteins