Absence of vas deferens
Introduction
Introduction to the lack of vas deferens The lack of vas deferens is a congenital malformation of the male reproductive system. It is an important cause of obstructive azoospermia and male infertility. It was discovered as early as the mid-18th century, but due to the limitations of diagnostic methods, until the first half of the 20th century. Ye, only 25 cases were reported in the world. Since then, with the improvement of male infertility diagnosis and treatment techniques, case reports have continued to increase. Since 1985, there have been nearly 170 cases of case and treatment research in China, but the cause of the disease has not yet been elucidated. In the past 10 years, with the gradual deepening of the etiology of the disease, the relationship between vas deferens and cystic fibrosis (CF) has been widely concerned. The in-depth study of the latter has led to the lack of congenital vas deferens. The molecular biology foundation has been initially revealed. basic knowledge The proportion of illness: 0.0035% Susceptible people: male Mode of infection: non-infectious complication:
Cause
Defective vas deferens
(1) Causes of the disease
Congenital vas deferens as a congenital malformation of the male reproductive system has been suspected to be related to genetic factors. For example, it has been found that the disease is clustered in some families, and cystic fibrosis and congenital vas deferens are found to be absent. Clinically closely related provides a powerful basis for the important role of genetic factors. Since the late 1980s, clinical and molecular genetic studies of cystic fibrosis have made significant progress, and the disease and congenital vas deferens are absent. Studies at the molecular level of the relationship have led to the clarification of the genetic basis of the absence of congenital vas deferens.
Cystic fibrosis is a common lethal autosomal recessive disorder. In Caucasians, the incidence rate is 1 in 2000 live births, and the frequency of causative gene carriers is as high as 1/22. The main clinical manifestations are chronic. Pulmonary diseases, insufficient pancreatic exocrine function, increased sweat electrolyte concentration and male infertility, the disease-causing gene was located in the long arm 3 region 1 band (7q31) of chromosome 7 in 1989, and has been cloned and sequenced. The full-length 250kb has 27 exons and the eDNA is 6129bp long. The encoded protein is called cystic fibrosis transport regulator (CFTR), which functions as a chloride channel. Currently, the gene has been found. More than 600 mutations and mutations covering the entire CFTR gene region, in which 70% of the mutations in Caucasians F508, ie, the 1653-l655 base pair of the 10th exon, deleted a coding peptide chain 508th styrene Codon for the amino acid.
In the study of cystic fibrosis, the majority of male patients were found to be infertile due to congenital vas deferens, indicating that the mutation of this gene is closely related to dysplasia dysplasia. Studies have confirmed the first type of congenital vas deferens If the patient is caused by a mutation in the CFTR gene, however, it is unclear whether the congenital vas deferens with no typical cystic fibrosis or physical appearance in a healthy male is associated with abnormalities in the CFTR gene. In 1983, Petit et al first reported that one case was not typical. Congenital vas deferens in patients with cystic fibrosis symptoms, accompanied by chromosome 7 abnormalities, namely inv (7) (p15, q32), inv (9) (p11, q13), at that time, because the CF gene has not been located Without considering its relationship with cystic fibrosis, it is now known that the CFTR gene is located at 7q31. This inversion of the chromosome arm may destroy the CFTR gene structure adjacent to chromosome 7 and cause congenital vas deferens. In the absence of this, this example suggests a possible association between a second type of congenital vas deferens and a CFTR gene abnormality, and secondly, with the clinical and molecular aspects of cystic fibrosis. In-depth study of the school has increasingly shown that the clinical manifestations of cystic fibrosis and the mutation genotype are closely related to the phenotype, that is, different mutant genotypes may lead to different clinical manifestations, the same mutant genotype in different individuals There may also be different clinical manifestations. Many researchers have conducted extensive mutation screening for exon and exon and intron cleavage sites of CFTR gene in such CBAVD patients, and found that such CBAVD is indeed CFTR. Mutations are closely related, at least 50% to 70%, and sometimes as high as 86% of these patients carry a CFTR mutation, and 10% of them are complex heterozygous mutations in the CFTR gene, ie, two chromosomes 7 each have a CFTR gene mutations, which are significantly different from the frequency of only 4% of CFTR gene mutation carriers in the normal population and 0.2% of the incidence, in addition to many new or compared CFTR genes in such CBAVD patients Rare mutations, which differ from the types and frequencies of mutations carried in patients with typical cystic fibrosis, further confirm the relationship between the mutant genotype and phenotype of cystic fibrosis System, i.e., causing the typical symptoms of cystic fibrosis mutations more common, and some are relatively rare mutations caused only more CBAVD.
In summary, the current consensus is that a considerable number of CBAVD men with no typical cystic fibrosis symptoms are a unique genetic group of cystic fibrosis. CBAVD is associated with lung disease and pancreatic function. An important phenotype of sexual fibrosis gene mutation, CFTR gene coding region mutation is one of the most important genetic causes of class 2 CBAVD.
In addition, in the study of CUAVD, the investigators found that when the patient's unilateral vas deferens was absent, the contralateral vas deferens had non-iatrogenic atresia at the groin or pelvic level, and the CFTR gene mutation rate was often as high as 89%, similar to CBAVD. However, it is significantly different from the normal population, which confirms that the CFTR gene coding region mutation is also one of the most important genetic causes of such CUAVD.
The current study of cystic fibrosis gene expression involves not only the coding region of the gene, but also a small number of non-coding regions, such as the 8th intron (introne 8) poly(T), expressed in the respiratory epithelium CFTR gene. The study confirmed that the allele 5T can affect the normal cleavage of the exon 9 of the gene, causing the transcription level to decrease, resulting in incomplete expression of the CFTR gene, causing a decrease in the level of CFTR protein, and triggering a series of clinical symptoms. It is believed that the 5T mutation of intrane 8 is one of the reasons for the clinical manifestation of cystic fibrosis. To explore the relationship between CBAVD and 5T mutation, some authors will study the CBAVD based on the mutation of cystic fibrosis gene. The results were divided into 3 groups: the first group accounted for about 15%, which is a complex heterozygote of CFTR gene mutation, and there is no 5T mutation; the second group accounts for about 60%, and there is a CFTR gene mutation, of which more than 60% are accompanied by another The 5T mutation in the CFTR gene; the third group accounted for about 25%, no other CFTR gene mutations were found, and the 5T mutation carrier frequency was about 25%, and even 5T homozygotes appeared, which shows that when both CFTR genes occur When a mutation occurs, the occurrence of CBAVD may Only related to the former, but not related to the 5T mutation; while the frequency of the 5T mutation carriers in the latter two groups was significantly higher than the carrier frequency of 5% in the normal population, showing extremely significant differences, suggesting that the presence of the 5T mutation on the CFTR gene introne 8 may be Another genetic cause of the absence of congenital vas deferens, and a mutation in the CFTR gene coding region plus a 5T mutation in the non-coding region of another CFTR gene may be the most common cause of congenital vas deferens.
Studies on the transcriptional level of CFF gene in CBAVD males also showed that when a CFTR gene mutation is heterozygous for a 5T mutation, its transcription product is only 6% to 16% normal, while the 5T mutation homozygous transcript is only normal. 24%, which further provides a theoretical basis for the important role of 5T mutation in the occurrence of congenital vas deferens, and to some extent reveals that cystic fibrosis, which is autosomal recessive, encodes only one gene. Region mutation is also the cause of congenital vas deferens. In addition, the transcription of this gene has certain tissue specificity, such as respiratory epithelial transcription level higher than epididymal epithelium, which may be a congenital vas deferens patient with CFTR gene mutation. One of the reasons for no other clinical manifestations.
A considerable proportion of simple congenital vas deferens is the result of CFTR gene mutation, a special phenotype of cystic fibrosis, but no CFTR gene mutation is found in another part of CBAVD and CUAVD patients. The reasons may be: 1CFTR gene is large, and the current polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and other techniques are still difficult to detect all mutations; 2 so far only outside the CFTR gene Exon, cleavage sites and a few neutrons have been subjected to mutation analysis. The presence of mutations in the promoter region or other regulatory sites cannot be ruled out, and the existence of the latter is possible. 3 In some families, the father and son, the siblings carry the same mutation. At the time, only one of them developed CBAVD, which indicates that in the absence of congenital vas deferens, in addition to CFTR gene abnormalities, there may be other genetic and environmental factors; 4 in congenital vas deferens and other urinary system malformations No mutation in the CFTR gene was found in patients with CUAVD who had a normal vas deferens (such as kidney deformity). Class independent of congenital vas deferens CFTR gene, there are also other causes of a supporting role.
In view of the fact that the molecular genetics research on the absence of congenital vas deferens is limited to gene coding and a few non-coding regions, in addition to continuing to detect more mutations from the CFTR gene coding region, the screening area should be gradually extended to gene initiation. Sub-regions and other regulatory regions, and study other genes outside the CFTR gene that may be associated with the absence of congenital vas deferens, thus more fully revealing the molecular genetic basis of congenital vas deferens.
(two) pathogenesis
Congenital vas deferens can be divided into:
1. Bilateral vas deferens (CBAVD) Because the bilateral renal tubes are not developed or underdeveloped, may be accompanied by epididymis, lack of seminal vesicles, rarely accompanied by renal deformity or lack of.
2. Unilateral vas deferens (CUAVD) is caused by unilateral middle renal tubules that are not developed or underdeveloped, often accompanied by ipsilateral ureteral buds that do not develop and cause renal dysplasia, ipsilateral kidney, ureter, vas deferens, epididymis None of them.
3. Part of the vas deferens can be divided into the absence of the scrotal segment of the vas deferens and the absence of the pelvic segment of the vas deferens. It may be caused by the sudden suspension of the middle kidney tube during the process of transformation into the vas deferens. The other vas deferens have a segment of the vas deferens. The luminal occlusion is blocked, and the middle kidney tube branch develops into a repeat vas deferens. In the reported cases of repeated vas deferens, most of the repeat sides have two testicles, each of which is connected to one testicle, and the vas deferens can deviate from the spermatic cord, and the ectopic opening In other parts, Kaplan reported 8 cases of ectopic dysplasia in 1978, of which 6 cases had other genitourinary malformations, and 3 cases had congenital anal atresia. Because the testes developed from the genital warts, the testes were generally deformed when the vas deferens were deformed. No abnormality.
According to the clinical manifestations and the relationship with cystic fibrosis, congenital vas deferens can be divided into two categories: the first category is clearly related to cystic fibrosis, patients with chronic lung disease, pancreatic function, etc., Typical cystic fibrosis symptoms such as elevated electrolyte concentration in sweat can be found during the examination; the second type of cause is unknown, and clinical infertility is often seen, but no other abnormalities are observed during physical examination.
Prevention
Deficiency of vas deferens
Need to pay attention to the diet, the other has no attention.
Complication
Deficiency of vas deferens Complication
When the unilateral vas deferens is absent, it may be accompanied by ipsilateral renal deficiency. The lack of vas deferens is often accompanied by the absence of seminal vesicles and some epididymis, but the absence of vas deferens is not associated with testicular defects. This is because the testes are from primitive gonads and epididymis. , the vas deferens, the seminal vesicle and the ejaculatory duct are from the middle kidney tube,
Symptom
Deficiency of the vas deferens Common symptoms
Bilateral vas deferens is often seen as a result of infertility after marriage. The patient is in good health, normal sexual life, can ejaculate, the scrotum is palpated in the spermatic cord and less than the vas deferens. The unilateral vas deferens is absent because the contralateral testicular vas deferens are normal and may not affect. Normal fertility, so no treatment, repeated vas deferens malformation without clinical symptoms, normal sexual life, and more found in the scrotum exploration surgery.
Examine
Examination of the absence of vas deferens
CBVAD has less semen, low pH, no sperm, lack of berry sugar or low content (<0.87g/ml or <13mol/1 ejaculation).
1. Testicular tissue examination of the seminiferous tubules can produce sperm, live sperm in the epididymal head puncture fluid.
2. Imaging examination B-ultrasound, CT, MRI and other visible cases have a lack of seminal vesicles or dysplasia; renal malformations, dysplasia, lack of one side of the kidney.
Diagnosis
Deficiency of vas deferens
1. Infertility in medical history.
2. Physical examination of the bilateral or unilateral scrotum can not touch the vas deferens, the epididymis head is enlarged, the body tail is absent.
3. Part of the deficiency is sometimes found by chance during surgery.
