Biallelic mutations in spermatogenesis and centriole-associated 1 like (SPATC1L) cause acephalic spermatozoa syndrome and male infertility / 亚洲男科学杂志(英文版)

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.

Case of bilateral Testicular Tumors subsequently diagnosed as Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

21-hydroxylase deficiency [21-OHD] caused congenital adrenal hyperplasia [CAH] is a group of autosomal recessive genetic disorders resulting from mutations in genes involved with cortisol [CO] synthesis in the adrenal glands. Testicular adrenal rest tumors [TARTs] are rarely the presenting symptoms of CAH. Here, we describe a case of simple virilizing CAH with TARTs, in a 15-year-old boy. The patient showed physical signs of precocious puberty. The levels of blood adrenocorticotropic hormone [ACTH], urinary 17-ketone steroids [17-KS], dehydroepiandrosterone sulfate [DHEA-S], and serum progesterone [PRGE] were elevated, whereas those of follicle-stimulating hormone [FSH], luteinizing hormone [LH], and CO were reduced. Computed tomography [CT] of the adrenal glands and magnetic resonance imaging [MRI] of the testes showed a soft tissue density [more pronounced on the right side] and an irregularly swollen mass [more pronounced on the left side], respectively. Pathological examination of a specimen of the mass indicated polygonal/circular eosinophilic cytoplasm, cord-like arrangement of interstitial cells, and lipid pigment in the cytoplasm. Immunohistochemistry results precluded a diagnosis of Leydig cell tumors. DNA sequencing revealed a hackneyed homozygous mutation, I2g, on intron 2 of the CYP21A2 gene. The patient's symptoms improved after a three-month of dexamethasone therapy. Recent radiographic data showed reduced hyperplastic adrenal nodules and testicular tumors. A diagnosis of TART should be considered and prioritized in CAH patients with testicular tumors. Replacement therapy using a sufficient amount of dexamethasone in this case helps combat TART

Familial fragile X syndrome: A pedigree analysis / 中华男科学杂志

<p><b>Objective</b>To investigate the clinical (including reproductive) manifestations and genetic characteristics of familial fragile X syndrome (FXS).</p><p><b>METHODS</b>We collected the clinical data about a case of familial FXS by inquiry, testicular ultrasonography, semen analysis, determination of sex hormone levels, and examinations of the peripheral blood karyotype and Y chromosome microdeletions. Using Southern blot hybridization, we measured the size of the CGG triple repeat sequence of the fragile X mental retardation-1 (FMR1) gene and determined its mutation type of the pedigree members with a genetic map of the FXS pedigree.</p><p><b>RESULTS</b>Among the 34 members of 4 generations in the pedigree, 3 males and 1 female (11.76%) carried full mutation and 9 females (26.47%) premutation of the FMR1 gene. Two of the males with full FMR1 mutation, including the proband showed a larger testis volume (>30 ml) and a higher sperm concentration (>250 ×10⁶/ml), with a mean sperm motility of 50.5%, a mean morphologically normal sperm rate of 17.5%, an average sperm nuclear DNA fragmentation index (DFI) of 18.5%, a low level of testosterone, normal karyotype in the peripheral blood, and integrity of the azoospermia factor (AZF) region in the Y chromosome. One of the second-generation females carrying FMR1 premutation was diagnosed with premature ovarian failure and another 3 with uterine myoma.</p><p><b>CONCLUSIONS</b>Some of the FXS males in the pedigree may present macroorchidism and polyzoospermia but with normal semen parameters. In the intergenerational transmission, premutation might extend to full mutation, with even higher risks of transmission and extension of mutation in males, especially in those with >80 CGG triple repeat sequences. Therefore, it is recommended that the couples wishing for childbearing receive genetic testing, clinical guidance, and genetic counseling before pregnancy and, if necessary, prenatal diagnosis and preimplantation genetic diagnosis.</p>

Current progress in cryopreservation of small numbers of sperm / 中华男科学杂志

Human sperm cryopreservation is an increasingly mature technique in assisted reproduction. However, conventional sperm cryopreservation is not suitable for the cryopreservation of small numbers of sperm. The solution to the cryopreservation of small numbers of sperm may contribute a lot to the clinical treatment of asthenospermia, oligospermia and azoospermatism. Recently, many researchers focus on searching for appropriate carriers for the cryopreservation of small numbers of sperm. This article outlines the effects of current cryopreservation methods including empty zona pellucida, microdrops, other mocrocarriers, testicular tissue cryopreservation and testicular sperm and epididymal sperm refrigeration.

Sperm selection in assisted reproductive technology: an update / 中华男科学杂志

Sperm selection plays an important role in assisted reproductive technology. In recent years, sperm evaluation is not limited to the assessment of sperm motility and morphology, but involves more other sperm characteristics such as sperm ultrastructure, DNA integrity, apoptosis and membrane. Assessment based on these characteristics is becoming the aim of sperm selection. This article gives an overview on several newly developed techniques for sperm selection according to different technical principles, such as electrophoretic separation, zeta potential, HA binding, Annexin V binding, intracytoplasmic morphologically selected sperm injection (IMSI) and microfluidic sperm sorter, which have all been applied to IVF or ICSI with the exception of microfluidic sperm sorter. It also introduces the advantages, disadvantages and application effects of these techniques.

Ring 22 chromosome syndrome induced azoospermia: a case report and literature review / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the clinical phenotype and genetic characteristics of an azoospermia patient with ring 22 chromosome syndrome.</p><p><b>METHODS</b>We analyzed the clinical data of an azoospermia patient with ring 22 chromosome syndrome and reviewed relevant literature.</p><p><b>RESULTS</b>The patient was a short 29-year-old male, with bilateral testes small in size and soft in texture. Seminal examination indicated azoospermia. Chromosome analysis showed the karyotype of the patient to be 46, XY, r (22) (p11, q25). The level of testosterone was low, and the testicular tissue was brittle and easy to break. Pathological microscopy revealed reduced number of Sertoli cells and germ cells in the seminiferous tubules and thinner layers of cells. All the germ cells were spermatogonia. Neither spermatocytes nor sperm cells were found, which suggested complete spermatogenic failure. Mild interstitial fibrosis was visible in part of the seminiferous tubule walls.</p><p><b>CONCLUSION</b>Patients with ring 22 chromosome syndrome usually represent normal clinical phenotypes. However, this kind of genetic abnormality often induces severe testicular damage and spermatogenic arrest, which may result in azoospermia.</p>

Multiplex ligation-dependent probe amplification for detecting AZF microdeletions on the Y chromosome in infertile men with azoospermia or severe oligozoospermia / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the possibility of applying multiplex ligation-dependent probe amplification (MLPA) to the detection of azoospermia factor (AZF) microdeletion on the Y chromosome in infertile men with azoospermia or severe oligozoospermia.</p><p><b>METHODS</b>DNA samples were obtained from 147 azoospermia or severe oligozoospermia patients and 154 normal controls. After denatured at 95 degrees C, the samples were hybridized to the specific probes designed for the AZF region. With the ligase, the hybrid products were amplified by a pair of universal primers labeled with FAM fluorescence, and then separated by capillary electrophoresis for data analysis. Meanwhile all the samples were subjected to multiplex-PCR (mPCR) analysis for sequence-tagged sites (STS) in the AZF region.</p><p><b>RESULTS</b>STS deletion was detected in 22 (15.0%) of the 147 patients but not in the normal controls. By MLPA, 40 (27.2%) of the patients were found with specific probe omission in the AZF region, as compared with 20 cases in the control group.</p><p><b>CONCLUSION</b>Compared with mPCR, MLPA has a better sensitivity in detecting AZF microdeletions, and it provides more precise genetic information on the AZF regions, which may contribute to in-depth exploration into the etiological mechanism of impaired spermatogenesis.</p>

Globozoospermia syndrome: an update / 中华男科学杂志

Globozoospermia syndrome is a rare teratozoospermia, with an incidence of less than 0.1%. It is characterized by round sperm head, absence of acrosome, and messy sperm body and tail, but without other special clinical features. The absence of acrosome could reduce the activation ability of oocytes, and consequently decrease their fertilization ability. The assisted reproductive technique remains the only means for such patients to produce offspring. The pathogenesis of globozoospermia syndrome is not yet clear, though it is found to be related with 4 genes in the mouse and 1 on the human autosome. This article gives an overview on the clinical features, pathogenesis and genetics of globozoospermia syndrome, as well as the fertilizability and reproductivity of such patients.

Congenital adrenal hyperplasia complicated by testicular adrenal rest tumors: one-case clinical analysis / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the early diagnosis and treatment of congenital adrenal hyperplasia (CAH) complicated by testicular adrenal rest tumors (TART).</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 1 case of late-onset CAH complicated by TART diagnosed and treated in Xiamen Women and Children Health Care Hospital.</p><p><b>RESULTS</b>The patient was a 15 years old boy, short statured and dark skinned, with skin pigmentation in the gum and external genital, secondary sex characteristics of the adult and irregular tubercles palpable in the bilateral testes. Laboratory examinations showed obviously increased levels of ACTH, 17-KS, DHEA-S and progesterone and evidently decreased levels of FSH, LH and CO. The low-dose dexamethasone suppression test reduced ACTH and DHEA-S to normal. Imaging examinations revealed soft tissue density in the bilateral adrenal glands, especially on the right, and irregularly increased volume of the bilateral testes, particularly on the left, with heterogeneous signals and septas and surrounded by the fluid signals. Histopathological examinations showed the eosinophilic cytoplasm to be polygon- or round-shaped, interstitium-like cells arranged in line, and lipopigment in the endochylema. Immunohistochemical results were negative for testicular interstitial cell tumor. The clinical signs of the patient were improved after 3 months of dexamethasone treatment, the hyperplastic nodules in the left testis decreased obviously and those in the right testis disappeared after 6 months, and the hyperplastic nodules in the adrenal glands vanished after 9 months.</p><p><b>CONCLUSION</b>Based on the clinical manifestations and the results of auxiliary examinations, this case was diagnosed as late-onset CAH complicated by TART, which was attributed to the continued surge of ACTH induced by corticoadrenal insufficiency. Sufficient dexamethasone treatment could make the TART decrease or disappear and the CAH vanish; it could also improve the clinical symptoms and bring the laboratory results to normal.</p>

Evolution and mutation of human Y chromosome and their relationship with male infertility / 中华男科学杂志

The Y chromosome evolves from euchromosome and accumulates a variety of male-specific genes, including SRY and many others that are related with spermatogenesis. The Y chromosome is distinguished from euchromosome by its characteristics of multiple copies of gene, multiple DNA sequences and high polymorphism. A lot of gene rearrangements occur during its evolution due to the specific gene structure in the Y chromosome. It has been discovered that one subset of such gene rearrangements induces Y-chromosome microdeletions that are involved in male infertility. Spermatogenesis is actually controlled by a network of genes, which may be located on the Y chromosome, euchromosomes or even the X chromosome. Further studies on the genomics and genes in the Y chromosome between sex chromosomes and/or between sex chromosome and euchromosomes will helps us to gain deeper insights into the molecular mechanism of male infertility.

Effects of cigarette, alcohol consumption and sauna on sperm morphology / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate effects of cigarette, alcohol consumption and sauna on sperm morphology.</p><p><b>METHODS</b>602 cases of male infertility were selected from our case database, who were divided into three subgroups: smoking (243) , drinking(224), sauna(135) and those without any of the above habits were taken as the corresponding controls. The sperm morphology were analyzed by automated sperm morphology analyzer(ASMA). A questionnaire was voluntarily filled out by patients in order to investigate cigarette, alcohol consumption and sauna frequency.</p><p><b>RESULTS</b>The normal morphologic sperm rates in cigarette, alcohol consumption and sauna groups were lower than those in the corresponding control groups, respectively(P <0.05, P <0.001). Percentages of irregularity head sperm were higher than those in normal controls, respectively(P <0.05).</p><p><b>CONCLUSION</b>Cigarette, alcohol consumption and sauna could affect sperm morphology, especially caused increasing of irregularity head sperm.</p>