会务通学术会议服务平台

标题： Idiopathic male infertility with a novel copy number variation in CATSPER2 (a case report)

讲者：陈厚仰

单位：江西省妇幼保健院

关键词：

CATSPER2 copy number variation idiopathic male infertility progesterone response whole-genome se

播放： 1222

论文摘要： STUDY QUESTION: Do genetic abnormalities in CATSPER (cation channel of sperm) genes associate with idiopathic male infertility with normal semen parameters and if so how do they affect male fertility?
SUMMARY ANSWER: A novel copy number variation in CATSPER2 causes idiopathic male infertility with normal semen parameters by disrupting sperm abilities of penetration viscous media and responses to progesterone.
WHAT IS KNOWN ALREADY: CATSPER is the principal Ca²⁺ channel to mediate extracellular Ca²⁺ influx into spermatozoa. Although several case reports have suggested the causal relationship between CATSPER disruption and human male infertility, whether genetic abnormalities in CATSPER genes associate with idiopathic male infertility with normal semen parameters remains unclear.
STUDY DESIGN, SIZE, DURATION: Spermatozoa were obtained from healthy fertile and infertile males attending the reproductive medical center at Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, China between January 2014 and June 2016. In total 120 infertile males and 20 healthy male spamles were selected to take part in the study according to their normal semen parameters.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Abnormalities in CATSPER current were directly assessed using whole-cell patch-clamp technique. The whole-genome sequencing and TaqMan^® copy number variation (CNV) assay were applied to identify the genetic variations. The expression of genes encoding CATSPER complex was measured by quantitative real-time PCR and western blot. Sperm response to progesterone in terms of increases of CATSPER current and intercellular Ca²⁺ concentration ([Ca²⁺]_i) as well as inducement of penetration ability and acrosome reaction were examined by means of whole-cell patch-clamp technique, single-sperm [Ca²⁺]_i imaging, penetration into methylcellulose assay and chlortetracycline staining, respectively.
MAIN RESULTS AND THE ROLE OF CHANCE: An infertile man with complete disruption of CATSPER current was screened. This individual has a novel CNV which loses one copy in region of 43894500 to 43950000 in chromosome 15 (GRCh37.p13 Primary Assembly, nsv3067119) containing the whole DNA sequence of CATSPER2. This CNV affected the expression of CATSPER2 resulting in dramatically low level of CATSPER2 proteins in the individual’s spermatozoa. Although this individual exhibited normal semen parameters, his spermatozoa showed impaired hyperactivation, and did not respond to progesterone, in terms of monovalent current potentiation, [Ca²⁺]_i increase, penetration ability enhancement and acrosome reaction inducement, which may explain the individual’s idiopathic infertility.
LIMITATIONS, REASONS FOR CAUTION: It requires more cases to support the CATSPER2 CNV identified in this study as a common cause for idiopathic male infertility with normal semen parameters, and thus caution must be taken when extrapolating this CNV as a biomarker for idiopathic male infertility.
WIDER IMPLICATIONS OF THE FINDINGS: The findings from the unique human CATSPER “knockout” model in this study not only confirms the essential roles of CATSPER in mediating progesterone response and regulating hyperactivation in human spermatozoa, but also unveils that disruption of CATSPER current is a significant factor causing idiopathic male infertility.