Oligoasthenozoospermia (OAT) is a common cause of male infertility, with most OAT patients resulting from genetic defects. In this study, we recruited a severe OAT patient and his family for genetic analysis, identifying a heterozygous RHOXF1 mutation (c.412 G>A p.Glu138Lys) in the patient and his brother, inherited from their mother who carried a heterozygous RHOXF1 mutation. The RHOXF1 mutation (c.412 G>A p.Glu138Lys) resulted in reduced testosterone secretion, elevated luteinizing hormone (LH) levels, disrupted sex hormone secretion, and inability to produce sperm. We reported for the first time that the RHOXF1 gene mutation (c.412 G>A p.Glu138Lys) caused severe OAT in human males. Our study not only contributes to expanding the spectrum of genetic defects associated with severe OAT but also facilitates accurate genetic screening and clinical diagnosis.
OBJECTIVE:To explore the clinical features and genetic basis of a male patient with Kennedy disease(KD) presenting as secondary infertility. METHODS:A male patient who had presented at Yantai Yuhuangding Hospital in August 2023 for secondary infertility for 5 years was selected as the study subject. Clinical data, laboratory findings, and auxiliary examination of the patient were collected. Peripheral blood samples were obtained from the patient and his family members. Following DNA extraction, whole-exome sequencing (WES) was carried out. Pathogenicity of candidate variant was predicted by bioinformatics analysis. Fluorescence probe PCR-capillary electrophoresis was employed to analyze the trinucleotide CAG repeat sequence variation in the AR gene to rule out dynamic mutation. This study was approved by the Ethics Committee of Yantai Yuhuangding Hospital (Ethics No.: 2024-697). RESULTS:The patient had presented with non-obstructive azoospermia and elevated androgen sensitivity index. Ultrasound scan indicated small testicular volume and seminal vesicle atrophy. WES and bioinformatics analysis revealed abnormal amplification in the patient's AR gene. Fluorescence probe PCR and capillary electrophoresis confirmed that both the proband and his nephew had harbored 52 CAG trinucleotide repeats in exon 1 of the AR gene, confirming the diagnosis of KD. The proband's mother, elder sister, and daughter were identified as carriers of the variant, while his second elder sister did not carry the mutation. CONCLUSION:As a rare X-linked recessive genetic disease, KD mainly manifests with muscle weakness, myasthenia gravis and myofascial tremor, while cases with infertility and non-obstructive azoospermia as the initial symptoms are rare and can be easily missed. Diagnosis made by genetic testing needs to be taken seriously by the clinicians.
Introduction: Varicocele is a dilatation of the internal spermatic vein and it is generally recognized as one cause of male infertility. This study aimed to analyze the roles of activating transcription factor 6 (ATF-6) in experimental varicocele-induced epididymal epithelial cells. Methods: Experimental left varicocele was established in rats through partial left renal vein ligation. At 8 weeks after surgery, the left epididymal damage was observed using H&E and TUNEL staining. The expressions of neutral alpha-glucosidase (NAG), ATF-6, tumor necrosis factor (TNF)-alpha, and phospho-nuclear factor (p-NF)-xB p65 (S536) in the left epididymis were measured by immunohistochemistry. ATF-6 silence in rat epididymal epithelial cells was established by ATF-6 siRNA transfection. The cells were treated with hypoxia for 24 h, and cell viability was measured by CCK-8, levels of NAG, TNF-alpha, and interleukin (IL)-8 in cells were measured by ELISA, levels of p-NF-xB p65 (S536)/NF-xB p65 protein in cells were measured by Western blotting. Results: The results showed that the experimental left varicocele induced hypertrophy and apoptosis of epididymal epithelial cells (p<0.05), and decreased the expressions of NAG in the epididymal epithelial cells compared with the sham-operated control rats (p<0.01). Meanwhile, the expressions of ATF-6, TNF-alpha, and p-NF-xB p65 (S536) were increased in the epididymal epithelial cells after the experimental left varicocele compared with the sham-operated control rats (p<0.05). In the hypoxia-treated cells, ATF-6 silence increased the cell viability and decreased the levels of TNF-alpha, IL-8, and p-NF-xB p65 (S536) compared with the control cells (p<0.05). Discussion: The ATF-6 pathway was activated in a rat's left varicocele-induced epididymal damage. Inhibition of the ATF-6 pathway might be a possible novel therapeutic approach for left varicocele-induced epididymal damage.
Dear Editor, Male infertility is a complex and multifactorial health problem with highly heterogeneous phenotypes,ranging from reduced sperm production to the complete absence of sperm in testis,and genetic factors play an important role in this problem.1 Patients with azoospermia have the highest risk of carrying genetic abnormalities,and this risk gradually decreases as sperm count increases.1 Due to the high throughput and low cost of next-generation sequencing(NGS)technology,many centers have used NGS to identify genetic defects associated with abnormal spermatogenesis.
This study aimed to evaluate the efficacy and safety of calcium ionophore during assisted oocyte activation (AOA). This meta-analysis contained randomized controlled trials and prospective observational and retrospective trials. The summary odds ratio (OR) with 95% confidence intervals (CIs) was calculated for clinical pregnancy rate and live birth rate. Both fixed and random effects models were applied. A total of 22 studies were included into this meta-analysis. Seventeen of the included studies showed that calcium ionophore increased the clinical pregnancy rate (OR, 2.14; 95% CI, 1.38–3.31). Similarly, 14 studies indicated that AOA with calcium ionophore during intracytoplasmic sperm injection (ICSI) improved the live birth rate considerably (OR, 2.65; 95% CI, 1.53–4.60). Moreover, fertilization, blastocyst formation, and implantation rate were higher after using AOA with calcium ionophore combined with ICSI. In addition, calcium ionophore did not increase top-quality embryo rate, cleavage rate, miscarriage rate, congenital birth defects, and neonatal sex ratio. Therefore, calcium ionophore followed by ICSI not only significantly improved live birth and overall pregnancy, but also did not affect the incidence of miscarriage, congenital birth defects, and neonatal sex ratio. This meta-analysis indicated that using calcium ionophore to activate oocytes was beneficial for couples with poor fertilization rates following ICSI.
Objective To explore the intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) method on the clinical outcomes of infertile women with ≤3 eggs retrieved. Study Design. We retrospectively analyzed a cohort of female patients who received IVF/ICSI to assist pregnancy with retrieved eggs ≤3. The general conditions, i.e., two pronuclei (2PN) fertilization rate, abnormal fertilization rate, high-quality embryo rate, cycle cancellation rate, pregnancy rate of fresh embryo transfer, cumulative pregnancy rate, and miscarriage were compared between the two groups. Results When the number of retrieved eggs was one, the fertilization rate of 2PN was higher and the cycle cancellation rate was lower in the ICSI group than in the IVF group (P < 0.05). The pregnancy rates of fresh embryo transfer, frozen-thawed embryo transfer, and the cumulative pregnancy rate were all higher in the ICSI group than in the IVF group (P < 0.05). When the number of retrieved eggs was two, the pregnancy rate of frozen-thawed embryo transfer and cumulative pregnancy rate in the ICSI group were higher than those in the IVF group (P < 0.05). When the number of retrieved eggs was three, the fertilization rate of 2PN and the pregnancy rate of frozen-thawed embryo transfer were higher in the ICSI group than those in the IVF group (all (P < 0.05)). Conclusions For patients with one egg retrieved, ICSI fertilization can reduce abnormal fertilization rate and cycle cancellation rate and improve cumulative pregnancy rate significantly enhancing patients' benefits. However, increasing the number of eggs retrieved decreases the advantages of ICSI fertilization.
This study aimed to evaluate the efficacy and safety of calcium ionophore during assisted oocyte activation (AOA). This meta-analysis contained randomized controlled trials and prospective observational and retrospective trials. The summary odds ratio (OR) with 95% confidence intervals (CIs) was calculated for clinical pregnancy rate and live birth rate. Both fixed and random effects models were applied. A total of 22 studies were included into this meta-analysis. Seventeen of the included studies showed that calcium ionophore increased the clinical pregnancy rate (OR, 2.14; 95% CI, 1.38-3.31). Similarly, 14 studies indicated that AOA with calcium ionophore during intracytoplasmic sperm injection (ICSI) improved the live birth rate considerably (OR, 2.65; 95% CI, 1.53-4.60). Moreover, fertilization, blastocyst formation, and implantation rate were higher after using AOA with calcium ionophore combined with ICSI. In addition, calcium ionophore did not increase top-quality embryo rate, cleavage rate, miscarriage rate, congenital birth defects, and neonatal sex ratio. Therefore, calcium ionophore followed by ICSI not only significantly improved live birth and overall pregnancy, but also did not affect the incidence of miscarriage, congenital birth defects, and neonatal sex ratio. This meta-analysis indicated that using calcium ionophore to activate oocytes was beneficial for couples with poor fertilization rates following ICSI.
Follicle-stimulating hormone (FSH) is commonly used in assisted reproductive technology to promote the development and maturation of follicles in female patients. However, there is no consensus on treating FSH in males with idiopathic oligoasthenoteratozoospermia (iOAT), especially in patients with normal serum FSH levels. To determine the role of FSH in improving semen quality in patients with iOAT, we conducted a detailed search in the commonly used database to find all studies on FSH in the treatment of iOAT. We compared the results, including semen volume, sperm count, sperm concentration, percentage of forward sperm motility, percentage of total sperm motility, percentage of normal forms and DNA fragmentation index (DFI) between the two groups treated with FSH or not. A total of 12 randomized controlled trials and one retrospective case-control study, including 924 people, were included in our meta-analysis. We found that sperm counts (MD 17.75; 95% CI 11.53-23.98 and p < 0.00001) were significantly increased in patients treated with FSH, along with improvements in sperm concentration (MD 4.52; 95% CI 1.46-7.58 and p = 0.004), percentage of normal forms (MD 2.87; 95% CI 0.19-5.56 and p = 0.04) and DFI (MD -12.62; 95% CI -19.27-5.97 and p = 0.002). However, we found no significant differences in the two groups' changes in other semen parameters. The use of FSH can improve some semen parameters in patients with iOAT, such as sperm count, percentage of normal forms, sperm concentration and DFI.
BackgroundMultiple morphological anomalies of the sperm flagella (MMAF) is a term used to describe abnormalities in sperm morphology, which lead to primary infertility in males. Intracytoplasmic sperm injection (ICSI) is an effective treatment for MMAF. However, ICSI failure rates remain high in MMAF patients. Our purpose was to investigate novel gene mutations in a cohort of nineteen patients with MMAF and assess the impact of these mutations on assisted reproductive therapy.MethodsWe recruited nineteen infertile patients with MMAF and twenty healthy men with proven fertility at the Affiliated Yantai Yuhuangding Hospital of Qingdao University. The morphology of the spermatozoa was observed using Papanicolaou staining and the ultrastructure of the spermatozoa was inspected using transmission electron microscopy. Gene mutations were evaluated using whole-exome sequencing and novel mutations were further validated in patients and their parents using Sanger sequencing. The effect of these novel mutation sites on the expression of DNAH1 was analysed using immunofluorescence, and the effect of these novel mutations on pregnancy outcome was analysed using intracytoplasmic sperm injection (ICSI). ResultsSpermatozoa from 19 patients presented with a typical MMAF phenotype including severe ultrastructural defects. We identified ten novel mutation sites in the DNAH1 locus from six of these patients, none of which were identified in DNAH1 or the other MMAF-related genes from the twenty men with proven fertility. In the sperm from these patients, DNAH1 was absent. Three patients with DNAH1 mutation who underwent intracytoplasmic sperm injection (ICSI) had a good outcome. ConclusionHere, we describe several novel compound heterozygous mutations and a novel homozygous mutation in DNAH1 from six independent MMAF patients. This study adds to the body of knowledge surrounding the genetic landscape of MMAF and DNAH1 improving our ability to diagnose and treat MMAF efficiently.
患者男性,26岁,因结婚1年多未育就诊.患者男性外观,喉结小,胡须稀少,身高170 cm,体重60 kg,无肘外翻,乳房未发育.专科检查:阴茎小,阴囊小,质软,阴毛稀少,呈倒三角形,尿道开口正常,附睾及精索无明显异常.B超检查:左右侧阴囊内分别见12 mm×7 mm、13 mm×6 mm睾丸样回声,前列腺大小25 mm×18 mm×15 mm,盆腔内未见明显卵巢及子宫样回声.精液检查:精液体积少,无精子.
Abstract Background The intraflagellar transport protein 140 homolog (IFT140) is involved in the process of intraflagellar transport (IFT), a process that is essential for the formation and maintenance of most eukaryotic cilia and flagella. Variants IFT140 have been reported to account for ciliopathy but association with male fertility has never been described in humans. Here we report the identification of two novel variants of IFT140 which caused spermatogenic dysfunction and male infertility. Methods Whole‐exome sequencing was performed in a 27‐year‐old infertile man presented with severe oligozoospermia, asthenozoospermia, and teratozoospermia (OAT) without other physical abnormality. Sanger sequencing was used to verify gene variants in the patient, his healthy brother, and their parents. Morphology and protein expression in the patient's sperm were examined by transmission electron microscopy (TEM) and immunofluorescence staining. Function of gene variants was predicted by online databases. Results Compound heterozygous variants of IFT140: exon16: c.1837G > A: p.Asp613Asn and exon31: c.4247G > A: p.Ser1416Asn were identified in the patient, both of which showed autosomal recessive inheritance in his family, and had extremely low allele frequency in the population. Morphological abnormalities of the head, nucleus, and tails and the absence of IFT140 from the neck and mid‐piece of the patient's spermatozoa were observed. Mutation Taster database predicted a high probability of damage‐causing by both variations. Conclusion This study for the first time reported IFT140 variants that cause infertility in humans.
Objective: To evalute the clinical outcomes of intracytoplasmic sperm injection(ICSI) for infertility male with severe asthenospermia induced by multiple morphological anomalies of the flagella (MMAF). Methods: The clinical data of 15 patient with MMAF were retrospectively analyzed, who underwent ICSI treatment using hyponotic swelling test the "live" sperm in the Department of Reproductive Medicine of Yantai Yuhuangding Hospital from January 2011 to December 2016. Another 30 obstructive azoospermia (OA)patients are matched strictly who also accepted ICSI in the same treatment time. The two groups were compared in the couples'age, the body mass index(BMI), the duration of infertility, the retrieved oocytes, the number of ICSI oocytes, and the rates of fertilization, cleavage, transferrable embryos, good embryos, embryos implanted, clinical pregncncy, early abortion, singleton and twins. Results: After 27 cycles of ICSI, all of the MMAF patients achieved clinical pregnancy, including 11 cases of live birth, 2 cases of spontaneous abortion, and 2 cases of pregnancy maintenance. There were no significant difference between MMAF and OA groups in the couples'age and BMI, or the numbers of retrieved oocytes and ICSI oocytes(P>0.05), but the differences in the infertility duration had statistical meaning(P<0.001). No statistical differences were observed among groups in ICSI fertility rate(92.0% vs 91.6%), clesvage rate(95.4% vs 96.5%), high-quality embryonic rate(56.5% vs 57.5%), good blastocyst rate(23/61 vs 35/94), embryo implantation rate(20/48 vs 35/75), early abortion rate(4/19 vs 8/36), clinical pregncncy rate(15/27 vs 28/50), singleton rate (10/13 vs 20/25)and twinning rate(3/13 vs 5/25)(P>0.05). Conclusions: MMAF may not affect ICSI treatment outcomes, but genetic defects can be transmitted through ICSI. The affected couples should be informed of the necessity of prenatal genetic diagnosis before embryo implantation and the inevitable vertical transmission of genetic problems to the offspring.
Oligoasthenoteratozoospermia (OAT) is characterized as low sperm count, decreased sperm motility and structural abnormalities of the sperm head in the same patient. However, very few studies reported the genetic alterations associated with OAT. Here we report a 38-year-old patient with OAT from a consanguineous family, with 2-6 million/mL sperm density, 2.1-3.8% normal sperm morphology and immotile sperm. Whole-exome sequencing (WES) identified homozygous variant c.1259A > G:p.Y420C in the TDRD6 gene. TDRD6 is a testis specific expressed protein that was localized to the chromatoid bodies in germ cells and played an important role in the nonsense-mediated decay pathway. This rare variant co-segregated with the OAT phenotype in this family. Bioinformatic analysis also suggested the variant a pathogenic mutation. Two intracytoplasmic sperm injection (ICSI) cycles were carried out in the patient's wife, but she did not become pregnant after embryo transfer. So the mutations in TDRD6 may be associated with human male infertility and early embryonic lethality.
Dear Editor, Male infertility, which affects approximately 20 million people worldwide, is commonly caused by spermatogenic dysfunctions, including severe oligozoospermia, cryptozoospermia, and nonobstructive azoospermia, which are largely genetic in origin.123 Here, we report a case of cryptozoospermia in a 33-year-old patient, who sought treatment for primary sterility that had been ongoing for 5 years. The patient had intercourse with his spouse without contraception two to three times per week, but they had not achieved pregnancy. The patient was born of consanguineous parents who were maternal cousins (Figure 1). He had no history of adverse sexual contact or inappropriate hobbies. He was 161 cm tall and weighed 80 kg, and his external genital organs were normally developed, with both testes around 6 ml in size, and no palpable abnormality in his bilateral spermatic veins.Figure 1: Pedigree chart of the patients. The arrow indicates the proband.The patient underwent three semen examinations in our hospital and other institutions. In our hospital, the semen analysis was carried out according to the guidelines in the WHO Laboratory Manual for the Examination and Processing of Human Semen.4 The patient's semen volume was 3.0–3.5 ml, pH 7.2–7.5, and spermatozoa were absent from his semen smear. Semen centrifugal sediment smear showed a sperm count of 0-2 cells per high-power field (HPF), and very few active spermatozoa were observed. Staining with Diff-Quik indicated normal morphology in 2.5%-4.0% of spermatozoa. Sex-hormone levels were follicle-stimulating hormone (FSH) 20.8 mIU ml−1 (reference value 1.5–12.4 mIU ml−1), luteinizing hormone (LH) 10.4 mIU ml−1 (reference value 1.7–8.6 mIU ml−1), testosterone (T) 2.9 ng ml−1 (reference value 2.5–8.4 ng ml−1), estradiol (E2) 40.5 pg ml−1 (reference value 7.6–42.6 pg ml−1), and prolactin (PRL) 5.1 ng ml−1 (reference value 2.6–13.1 ng ml−1). No abnormalities were revealed by peripheral-blood chromosomal-karyotype analysis. Y-chromosome-microdeletion screening was carried out according to the European Academy of Andrology (EAA) guidelines by real-time fluorescent PCR using the Y Chromosomal Microdeletion Test Kit (Shanghai Tellgen Corporation, Shanghai, China), which detected the sY84 and sY86 sequence-tagged sites (STSs) of azoospermia factor a (AZFa), the sY127 and sY134 STSs of AZFb, and the sY254 and sY255 STSs of AZFc. All six STSs were present, indicating that the patient did not have a Y-chromosome microdeletion. The initial clinical diagnosis was primary infertility with cryptozoospermia, bilateral testicular dysplasia, and high-gonadotropin gonadal-function decline. With the approval of the Ethics Committee of Yantai Yuhuangding Hospital and with the patient's informed consent, peripheral blood was extracted for exome sequencing. Because the patient's parents were consanguineous, bioinformatics analysis was performed to identify inheritance of recessive characteristics. All the homozygous mutations were screened to identify potentially pathogenic gene alterations related to spermatogenesis, through phenotype and genotype correlation analysis. A novel nonsense mutation was identified at exon 1:c.6934G>A (p.R2312X) of the testis-expressed 15 (TEX15) gene, which resulted in a truncated TEX15 protein. This mutation was confirmed by Sanger sequencing. Both parents of the proband were carriers of this mutation (Figure 2). We speculated that this mutation was at least in part the cause of the spermatogenic dysfunction. Because of the extremely limited availability of the patient's spermatozoa, detection of TEX15 mRNA or TEX15 protein in spermatozoa was not possible.Figure 2: Sanger-sequencing results showing the homozygous c.6934G>A mutation in the proband and the heterozygous c.6934G>A mutation in the parents of proband, as well as the normal control.Spermatogenesis is a highly complex process of cell differentiation, which is necessary for the formation of haploid spermatozoa. The core of this process is meiosis in spermatocytes, during which synapsis and recombination of homologous chromosomes occur. TEX15 was first identified as a protein that is required for chromosomal synapsis and meiotic recombination in 2008.5 In TEX15-deficient male mice, DNA double-strand breaks (DSBs) are formed and not repaired, suggesting that TEX15 functions in the repair of DSBs via regulation of the loading of DNA repair proteins (RAD51 and DMC1) onto sites of DSBs. Homozygous deletion of TEX15 in mice also leads to significantly reduced testis volume.5 In an analysis of single-nucleotide polymorphisms (SNPs) in TEX15, rs323346 and rs323347 were identified as genetic risk factors for spermatogenic failure in the Chinese Han population.6 In 2015, Okutman and colleagues reported that a nonsense mutation (c.2130T>G, p.Y710X) in TEX15 caused infertility in three of seven brothers in a Turkish family with consanguineous parents.7 The sperm concentrations of patients with TEX15 mutations declined over time, and early-stage sperm cryopreservation was recommended.7 In summary, our study identified a novel homozygous nonsense mutation in TEX15 in a patient with cryptozoospermia. This mutation could be the cause of cryptozoospermia, with TEX15 deficiency resulting in the failure of spermatogenesis. The mutation was inherited from the patient's parents, who were both heterozygous carriers, indicating a recessive pattern of inheritance. With the development of precision medicine, TEX15 could become a clinical marker for detection of nonobstructive azoospermia or cryptozoospermia. AUTHOR CONTRIBUTIONS YWS and ZLG designed the study; XW analyzed data and wrote the manuscript; HRJ analyzed high-throughput sequencing data and screened for candidate genes; YQC extracted DNA and performed Sanger sequencing; and JC collect clinical data. All authors read and approved the final manuscript. COMPETING INTERESTS All authors declared no competing interests. ACKNOWLEDGMENTS This study was supported by the Science and Technology Planning Project (Grant No. 3502Z20154033), the Major/Important Disease Research Project (Grant No. 3502Z20159022), the Young/Middle-aged Talent Cultivation Project (Grant No. 2015-ZQN-JC-44), and the Science and Technology Guided Project of Fujian Province (Project No. 2016Y0101).
Multiple morphological abnormalities of the sperm flagella (MMAF) is a rare disease that causes primary infertility. However, the genetic causes for approximately half of MMAF cases are unknown. Whole exome sequencing analysis of the 27 patients with MMAF identified several CFAP44 mutations (3 homozygous: c.2935_2944del: p.D979*, c.T1769A: p.L590Q, c.2005_2006del: p.M669Vfs*13; and putative compound heterozygous: c.G3262A: p.G1088S and c.C1718A: p.P573H.) and CFAP43 acceptor splice-site deletion (c.3661-2A>-) mutations in 5 and 1 patients, respectively. Real-time quantitative polymerase chain reaction assays also demonstrated that CFAP44 expression was very weak in patient (P)1 and P3, and CFAP43 expression was lower in P6 than in the control. Immunofluorescence analysis of CFAP43 showed lower CFAP43 protein expression levels in P6 than in the normal control. This study demonstrated that biallelic mutations in CFAP44 and CFAP43 cause MMAF. These results provide researchers with a new insight to understand the genetic etiology of MMAF and to identify new loci for genetic counselling of MMAF.
在成年后就诊的男性21-羟化酶缺陷症患者临床少见,本文报道了1例合并无精症的单纯男性化型21-羟化酶缺陷症患者的临床资料.
FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone (T) and estradiol (E-2) levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin (hCG) tests. Both follicle stimulating hormone (FSH) and luteinizing hormone (LH) showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E-2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man's sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis.
Zuckerkandl结节(Zuckerkandle tubercle,ZT)是甲状腺一个特殊的解剖特征,由甲状腺后外侧突起形成的部分,与甲状腺喉返神经及上甲状腺旁腺有重要的解剖关系. 1 历史 Zuckerkandl是澳大利亚解剖学家,在1902年首先提出并将其作为"甲状腺后侧部分"结节加以命名[1].1867年,Madelung曾把ZT称为"甲状腺后角".1938年,Gilmour报道了ZT与甲状旁腺与喉返神经的解剖关系.