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学科主题: 基础医学
题名:
Lack of testicular seipin causes teratozoospermia syndrome in men
作者: Jiang, Min1; Gao, Mingming2,3; Wu, Chaoming4; He, Hui1; Guo, Xuejiang1; Zhou, Zuomin1; Yang, Hongyuan5; Xiao, Xinhua6,7; Liu, George2,3; Sha, Jiahao1
刊名: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
发表日期: 2014-05-13
DOI: 10.1073/pnas.1324025111
卷: 111, 期:19, 页:7054-7059
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: CONGENITAL GENERALIZED LIPODYSTROPHY ; HSL-DEFICIENT MICE ; SHOTGUN LIPIDOMICS ; MALE REPRODUCTION ; ADIPOSE-TISSUE ; GENE ; PROTEIN ; MOUSE ; IDENTIFICATION ; FERTILITY
英文摘要:

Obesity impairs male fertility, providing evidence for a link between adipose tissue and reproductive function; however, potential consequences of adipose tissue paucity on fertility remain unknown. Lack of s.c. fat is a hallmark of Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), which is caused by mutations in BSCL2-encoding seipin. Mice with a targeted deletion of murine seipin model BSCL2 with severe lipodystrophy, insulin resistance, and fatty liver but also exhibit male sterility. Here, we report teratozoospermia syndrome in a lipodystrophic patient with compound BSCL2 mutations, with sperm defects resembling the defects of infertile seipin null mutant mice. Analysis of conditional mouse mutants revealed that adipocyte-specific loss of seipin causes progressive lipodystrophy without affecting fertility, whereas loss of seipin in germ cells results in complete male infertility and teratozoospermia. Spermatids of the human patient and mice devoid of seipin in germ cells are morphologically abnormal with large ectopic lipid droplets and aggregate in dysfunctional clusters. Elevated levels of phosphatidic acid accompanied with an altered ratio of polyunsaturated to monounsaturated and saturated fatty acids in mutant mouse testes indicate impaired phospholipid homeostasis during spermiogenesis. We conclude that testicular but not adipose tissue-derived seipin is essential for male fertility by modulating testicular phospholipid homeostasis.

语种: 英语
所属项目编号: 2011CB944304 ; 2011CB503900 ; 2012CB517505 ; 81222006 ; 30930037 ; 81121061
项目资助者: National Key Basic Research Program Grant ; Major National Basic Research Program of the People&prime ; s Republic of China ; National Natural Science Foundation of the People&prime ; s Republic of China
WOS记录号: WOS:000335798000071
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62260
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Nanjing Med Univ, State Key Lab Reprod Med, Dept Histol & Embryol, Nanjing 210029, Jiangsu, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100083, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100083, Peoples R China
4.Wenzhou Med Univ, Affiliated Hosp 2, Dept Endocrinol, Wenzhou 325027, Peoples R China
5.Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia
6.Chinese Acad Med Sci, Peking Union Med Coll Hosp, Minist Hlth, Dept Endocrinol,Key Lab Endocrinol, Beijing 100730, Peoples R China
7.Peking Union Med Coll, Beijing 100730, Peoples R China

Recommended Citation:
Jiang, Min,Gao, Mingming,Wu, Chaoming,et al. Lack of testicular seipin causes teratozoospermia syndrome in men[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2014,111(19):7054-7059.
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