PDF(Pubmed)
Abstract：
Male 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.
Whole 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.
In 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.
Biallelic 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.
Whole 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.
In 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.
Biallelic 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.
摘要：
男性不育是由复杂和多因素的病理状况引起的严重健康问题。遗传因素是男性不育的主要原因。CEP70，一种中心体蛋白，据报道，在小鼠的雄性生殖中起重要作用。然而,CEP70在男性不育中的作用是有限的。
■使用全外显子组测序和Sanger测序来鉴定不育患者的遗传原因。巴氏染色，进一步进行扫描电子显微镜和透射电子显微镜观察患者精子的形态和超微结构缺陷。免疫荧光染色用于检测鉴定的变体的致病性和CEP70在睾丸中的特定表达。
■在这项研究中，我们在两个无关的少弱精子症不育男性个体中发现了CEP70的双等位基因突变,并遵循一种隐性遗传模式.巴氏染色，扫描电子显微镜和透射电子显微镜显示，患者精子的顶体和鞭毛的形态和超微结构缺陷与Cep70-/-雄性小鼠极为相似。免疫荧光染色结果表明，CEP70在对照精子的顶体和鞭毛中正常表达，但在携带CEP70变异的患者精子中几乎检测不到。我们还探索了CEP70在人和小鼠精子发生过程中的特定表达模式。
■CEP70的双等位基因突变可能是人类男性不育的新遗传原因，这可能是遗传咨询和男性不育诊断的基础。
■使用全外显子组测序和Sanger测序来鉴定不育患者的遗传原因。巴氏染色，进一步进行扫描电子显微镜和透射电子显微镜观察患者精子的形态和超微结构缺陷。免疫荧光染色用于检测鉴定的变体的致病性和CEP70在睾丸中的特定表达。
■在这项研究中，我们在两个无关的少弱精子症不育男性个体中发现了CEP70的双等位基因突变,并遵循一种隐性遗传模式.巴氏染色，扫描电子显微镜和透射电子显微镜显示，患者精子的顶体和鞭毛的形态和超微结构缺陷与Cep70-/-雄性小鼠极为相似。免疫荧光染色结果表明，CEP70在对照精子的顶体和鞭毛中正常表达，但在携带CEP70变异的患者精子中几乎检测不到。我们还探索了CEP70在人和小鼠精子发生过程中的特定表达模式。
■CEP70的双等位基因突变可能是人类男性不育的新遗传原因，这可能是遗传咨询和男性不育诊断的基础。
