The study found a new disease-caused gene for weak malformation sperm disease

。 CFAP58 gene mutation through the sperm tail axle assembly abnormalities and mitochondrial abnormal development led to MMAF
Mr. Wang from Henan Province is a serious patient with weak deformity sperm disease, has been transferred to a number of reproductive medicine centers, adhere to more than 2 years of drug treatment, has not been able to improve sperm quality.
generally speaking, infertility caused by non-genetic factors may be intervened by means of medication or surgery. Infertility, which may be caused by genetic factors, begins with finding specific disease-causing genes and then choosing assisted reproductive techniques accurately to help them reproduce. He Xiaojin, deputy director of the First Affiliated Hospital of Anhui Medical University, told China Science Daily.
recent years, The team of Cao Yunxia, president and professor of Anhui Medical University, has been working on the study of weak malformation sperm disease and has identified a number of disease-causing genes that cause multiple morphological abnormalities (MMAF) of sperm whiplash. Recently, they identified the disease-caused gene CFAP58 for the first time internationally, and the results were published online August 12 in the American Journal of Human Genetics., the global incidence of infertility has increased year by year, affecting 10 to 15 per cent of couples of childbearing age. The World Health Organization lists infertility as one of the three major diseases affecting the health of human life today.
, male infertility accounts for about 40%-50%, often manifested as less sperm, weak sperm, abnormal sperm disease or a variety of combinations. MMAF is a kind of severe weak deformity sperm disease, due to sperm whiplash appears short tail, curly tail, no tail, fold tail and irregular tail and other deformities, resulting in sperm activity and fertilization ability decreased.
have suggested that most of the causes of MMAF are closely related to genetic variation. However, due to the complex structure of sperm, involving a wide variety of genes, there are still 30%-40% of MMAF patients genetic causes are not clear. The study of genetic causes and pathogenesies is also a hot topic in international reproductive medicine research.
2-3 years, we accumulated about 90 patients, and after all-exon sequencing and genetic analysis, we found that 5 patients carried the CFAP58 gene double-equal mutation. He Xiaojin, co-first author of this article, said.
In the human genome, the exon region is a key area that determines the physiological characteristics of the human body, he said, "and for genetic diseases, the target is generally on the exon region, because it is a region that directly encodes genes and is directly related to protein translation." The amount of data analysis is relatively small, avoiding redundant information and making it more suitable for clinically effective search for disease-caused genes. Of
five patients with the CFAP58 mutation, four had parents who were married to close relatives and were infertile through a recessive genetic pattern passed on to their children. He Xiaojin said.using transmission mirror technology and molecular biology, the researchers observed sperm morphology that was 5,000-20,000 times larger.
cross-section at the normal sperm tail, showing the structure of 9 pairs of micro-tubes around 1 pair of central diodes, it is this arrangement pattern that makes the tail move freely. The micro-tube arrangement structure in patients with CFAP58 mutation is chaotic, in the vertical surface, mitochondrial symmetry in normal sperm, and mitochondrial arrangement in patients with CFAP58 mutation is different degrees of loss, and the arrangement is also disordered.
" after we carried out sperm immunofluorescence staining and immunoprinting experiments, found that sperm tail micro-tubes and mitochondrial marker proteins are reduced or not expressed, which further indicates that CFAP58 protein is affected by the arrangement of the arrangement of the sperm tail silk assembly and mid-stage mitochondrial development abnormalities, resulting in sperm motor dysfunction and malformation, resulting in male infertility. Lu Mingrong, an associate professor at Anhui Medical University and co-author of the paper, told China Science Daily.
animal experiments showed that the male mice knocked out by the CFAP58 gene were completely infertile, the sperm concentration was significantly reduced, the vitality was almost zero, and the tail showed deformities such as short tails and curly tails consistent with the patients." in clinical treatment, the most important thing is to find the right cause. Timely detection of accurate disease-caused genes for patients can not only help patients avoid unnecessary drug treatment, but also for patients to recommend appropriate "test-tube" technology to provide a basis. He Xiaojin said.
the discovery and identification of the CFAP58 gene provides theoretical support for genetic consultation, molecular diagnosis and clinical treatment of weak malformation sperm disease, which can help patients take fewer detours. He said.
Cao Yunxia, one of the co-authors of this paper, said, "The research team will study the superstructive structure of sperm and the mechanism of motor function regulation in depth, to provide more theoretical basis for understanding the mystery of sperm." (Source: Liu Runan, China Science Journal)
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