• PMID: 32124190
• Gene Name: SPAG6
• Condition: Asthenoteratospermia
• Association: Associated
• Mutation: c.143_145del: p.48_49del, c.585delA: p.Lys196Serfs*6
• Population size: 215
• Population details: 215 oligo-asthenospermia (OAT) patients
• Sex: Male
• Infertility type: Male infertility

Patients with severe asthenoteratospermia carrying SPAG6 or RSPH3 mutations have a positive pregnancy outcome following intracytoplasmic sperm injection

Wu H, Wang J, Cheng H, Gao Y, Liu W, Zhang Z, Jiang H, Li W, Zhu F, Lv M, Liu C, Tan Q, Zhang X, Wang C, Ni X, Chen Y, Song B, Zhou P, Wei Z, Zhang F, He X, Cao Y.

PURPOSE: To investigate the relation between mutations in ciliopathy-related SPAG6 and RSPH3 and male infertility with severe asthenoteratospermia characterized by multiple flagellar malformations and reveal the intracytoplasmic sperm injection (ICSI) outcomes of those primary ciliary dyskinesia (PCD) patients. METHODS: Whole-exome sequencing was applied to identify the pathogenic genes for the five PCD patients. The ICSI outcomes of those patients were compared with eight DNAH1-mutated patients and 215 oligo-asthenospermia (OAT) patients. RESULTS: We identified, for the first time, the compound heterozygous SPAG6 mutations (c.143_145del: p.48_49del, c.585delA: p.Lys196Serfs*6) in a sporadic PCD patient. Further, a novel homozygous nonsynonymous RSPH3 mutation (c.C799T: p.Arg267Cys) was identified in another PCD patient with consanguineous parents. The pathogenicity of these mutations in the assembly of sperm flagella was confirmed by flagellar ultrastructure analysis, immunofluorescence, and quantitative real-time PCR. All five patients underwent six ICSI cycles. The fertilization rate, blastocyst development rate, and clinical pregnancy rate were 69.3%, 50.0%, and 66.7%, respectively. Four of the five couples, including the subjects carrying mutations in SPAG6 or RSPH3, got healthy children born after ICSI. Additionally, the ICSI outcomes of the five PCD couples were statistically comparable with those of the eight DNAH1-mutated couples and the 215 OAT couples. CONCLUSIONS: Mutations in ciliopathy-related SPAG6 and RSPH3 cause severe asthenoteratospermia characterized by multiple flagellar malformations, resulting in sterility. ICSI is an optimal management with a positive pregnancy outcome. FAU - Wu, Huan AU - Wu H AUID- ORCID: 0000-0002-0009-3839 AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Wang, Jiajia AU - Wang J AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Cheng, Huiru AU - Cheng H AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Gao, Yang AU - Gao Y AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. FAU - Liu, Wangjie AU - Liu W AD - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China. AD - Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai, 200011, China. AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211116, China. FAU - Zhang, Zhiguo AU - Zhang Z AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Jiang, Huanhuan AU - Jiang H AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Li, Weiyu AU - Li W AD - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China. AD - Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai, 200011, China. AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211116, China. FAU - Zhu, Fuxi AU - Zhu F AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Lv, Mingrong AU - Lv M AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Liu, Chunyu AU - Liu C AD - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China. AD - Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai, 200011, China. AD - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230061, China. AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211116, China. FAU - Tan, Qing AU - Tan Q AD - Anhui Provincial Human Sperm Bank, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. FAU - Zhang, Xiaofeng AU - Zhang X AD - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230061, China. FAU - Wang, Chao AU - Wang C AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Ni, Xiaoqing AU - Ni X AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. FAU - Chen, Yujie AU - Chen Y AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. FAU - Song, Bing AU - Song B AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Zhou, Ping AU - Zhou P AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Wei, Zhaolian AU - Wei Z AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. AD - Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China. AD - Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. FAU - Zhang, Feng AU - Zhang F AD - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China. AD - Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai, 200011, China. AD - State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211116, China. FAU - He, Xiaojin AU - He X AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. hxj0117@126.com. AD - NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. hxj0117@126.com. AD - Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China. hxj0117@126.com.