Identification of biallelic variations of CEP70 in patients with male infertility
IntroductionMale infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP7...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1133222/full |
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| author | Tiechao Ruan Tiechao Ruan Yihong Yang Chuan Jiang Gan Shen Dingming Li Ying Shen |
| author_facet | Tiechao Ruan Tiechao Ruan Yihong Yang Chuan Jiang Gan Shen Dingming Li Ying Shen |
| author_sort | Tiechao Ruan |
| collection | DOAJ |
| description | IntroductionMale infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited.MethodsWhole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis.ResultsIn this study, we identified biallelic mutations of CEP70 in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in Cep70−/− male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying CEP70 variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice.ConclusionsBiallelic mutations of CEP70 might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility. |
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| language | English |
| last_indexed | 2024-04-10T04:37:43Z |
| publishDate | 2023-03-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-a22ce557137a4c25a9f25dff99e475a72023-03-09T16:41:42ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-03-011410.3389/fendo.2023.11332221133222Identification of biallelic variations of CEP70 in patients with male infertilityTiechao Ruan0Tiechao Ruan1Yihong Yang2Chuan Jiang3Gan Shen4Dingming Li5Ying Shen6Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, ChinaReproduction Medical Center of West China Second University Hospital, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, ChinaKey Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, ChinaKey Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, ChinaHuman Sperm Bank, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, ChinaIntroductionMale infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited.MethodsWhole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis.ResultsIn this study, we identified biallelic mutations of CEP70 in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in Cep70−/− male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying CEP70 variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice.ConclusionsBiallelic mutations of CEP70 might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility.https://www.frontiersin.org/articles/10.3389/fendo.2023.1133222/fullmale infertilityoligoasthenoteratozoospermiarecessive inheritanceCEP70WES |
| spellingShingle | Tiechao Ruan Tiechao Ruan Yihong Yang Chuan Jiang Gan Shen Dingming Li Ying Shen Identification of biallelic variations of CEP70 in patients with male infertility Frontiers in Endocrinology male infertility oligoasthenoteratozoospermia recessive inheritance CEP70 WES |
| title | Identification of biallelic variations of CEP70 in patients with male infertility |
| title_full | Identification of biallelic variations of CEP70 in patients with male infertility |
| title_fullStr | Identification of biallelic variations of CEP70 in patients with male infertility |
| title_full_unstemmed | Identification of biallelic variations of CEP70 in patients with male infertility |
| title_short | Identification of biallelic variations of CEP70 in patients with male infertility |
| title_sort | identification of biallelic variations of cep70 in patients with male infertility |
| topic | male infertility oligoasthenoteratozoospermia recessive inheritance CEP70 WES |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1133222/full |
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