<i>SEPT14</i> Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity
The main objective of this study was to evaluate the potential genetic effects of <i>SEPT14</i> on male infertility through sequencing the <i>SEPT14</i> coding region. To address this research gap, 254 men with sperm abnormalities and 116 normozoospermic men were recruited, a...
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doaj-89f0e544e3d94d0f889e94415461463c2020-11-24T21:26:47ZengMDPI AGJournal of Clinical Medicine2077-03832019-08-0189129710.3390/jcm8091297jcm8091297<i>SEPT14</i> Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA IntegrityYa-Yun Wang0Tsung-Hsuan Lai1Mei-Feng Chen2Hui-Ling Lee3Pao-Lin Kuo4Ying-Hung Lin5Department of Chemistry, Fu Jen Catholic University, New Taipei City 24205, TaiwanDepartment of Obstetrics and Gynecology, Cathay General Hospital, Taipei 10630, TaiwanBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan County 83301, TaiwanDepartment of Chemistry, Fu Jen Catholic University, New Taipei City 24205, TaiwanDepartment of Obstetrics & Gynecology, National Cheng Kung University, Tainan 70101, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 24205, TaiwanThe main objective of this study was to evaluate the potential genetic effects of <i>SEPT14</i> on male infertility through sequencing the <i>SEPT14</i> coding region. To address this research gap, 254 men with sperm abnormalities and 116 normozoospermic men were recruited, and the whole-coding regions of <i>SEPT14</i> were sequenced. Two heterozygous mutations, p.Ala123Thr (3/254 vs. 0/116) and p.Ile333Thr (3/254 vs. 0/116), were identified in these cases. A high percentage of defective sperm heads was found in sperm with mutated <i>SEPT14</i>. Both mutations are highly evolutionarily conserved among vertebrates. The results of a fine morphological and chromatin structural analysis indicated severely malformed sperm heads with abnormal chromatin packaging through transmission electron microscopy and Toluidine blue staining. Compared with controls, high DNA fragmentation was demonstrated in sperm from cases carrying <i>SEPT14</i> mutations using the comet assay. In addition, these two mutations in <i>SEPT14</i> affected its polymerization ability in vitro. These data revels that the two <i>SEPT14</i> missense mutations impaired sperm head morphology and induced DNA damage. Our study suggests that genetic variant of <i>SEPT14</i> is one of the effects for human sperm formation and male fertility.https://www.mdpi.com/2077-0383/8/9/1297male infertilityteratozoospermiaseptin<i>SEPT14</i>DNA damage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ya-Yun Wang Tsung-Hsuan Lai Mei-Feng Chen Hui-Ling Lee Pao-Lin Kuo Ying-Hung Lin |
spellingShingle |
Ya-Yun Wang Tsung-Hsuan Lai Mei-Feng Chen Hui-Ling Lee Pao-Lin Kuo Ying-Hung Lin <i>SEPT14</i> Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity Journal of Clinical Medicine male infertility teratozoospermia septin <i>SEPT14</i> DNA damage |
author_facet |
Ya-Yun Wang Tsung-Hsuan Lai Mei-Feng Chen Hui-Ling Lee Pao-Lin Kuo Ying-Hung Lin |
author_sort |
Ya-Yun Wang |
title |
<i>SEPT14</i> Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity |
title_short |
<i>SEPT14</i> Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity |
title_full |
<i>SEPT14</i> Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity |
title_fullStr |
<i>SEPT14</i> Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity |
title_full_unstemmed |
<i>SEPT14</i> Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity |
title_sort |
<i>sept14</i> mutations and teratozoospermia: genetic effects on sperm head morphology and dna integrity |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2019-08-01 |
description |
The main objective of this study was to evaluate the potential genetic effects of <i>SEPT14</i> on male infertility through sequencing the <i>SEPT14</i> coding region. To address this research gap, 254 men with sperm abnormalities and 116 normozoospermic men were recruited, and the whole-coding regions of <i>SEPT14</i> were sequenced. Two heterozygous mutations, p.Ala123Thr (3/254 vs. 0/116) and p.Ile333Thr (3/254 vs. 0/116), were identified in these cases. A high percentage of defective sperm heads was found in sperm with mutated <i>SEPT14</i>. Both mutations are highly evolutionarily conserved among vertebrates. The results of a fine morphological and chromatin structural analysis indicated severely malformed sperm heads with abnormal chromatin packaging through transmission electron microscopy and Toluidine blue staining. Compared with controls, high DNA fragmentation was demonstrated in sperm from cases carrying <i>SEPT14</i> mutations using the comet assay. In addition, these two mutations in <i>SEPT14</i> affected its polymerization ability in vitro. These data revels that the two <i>SEPT14</i> missense mutations impaired sperm head morphology and induced DNA damage. Our study suggests that genetic variant of <i>SEPT14</i> is one of the effects for human sperm formation and male fertility. |
topic |
male infertility teratozoospermia septin <i>SEPT14</i> DNA damage |
url |
https://www.mdpi.com/2077-0383/8/9/1297 |
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