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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.

Kartagener's syndrome (KS) is an autosomal recessive genetic disease accounting for approximately 50% of the cases of primary ciliary dyskinesia (PCD). As it is accompanied by many complications, PCD/KS severely affects the patient's quality of life. Therapeutic approaches for PCD/KS aim to enhance prevention, facilitate rapid definitive diagnosis, avoid misdiagnosis, maintain active treatment, control infection and postpone the development of lesions. In male patients, sperm flagella may show impairment in or complete absence of the ability to swing, which ultimately results in male infertility. Assisted reproductive technology will certainly benefit such patients. For PCD/KS patients with completely immotile sperm, intracytoplasmic sperm injection may be very important and even indispensable. Considering the number of PCD/KS susceptibility genes and mutations that are being identified, more extensive genetic screening is indispensable in patients with these diseases. Moreover, further studies into the potential molecular mechanisms of these diseases are required. In this review, we summarize the available information on various aspects of this disease in order to delineate the therapeutic objectives more clearly, and clarify the efficacy of assisted reproductive technology as a means of treatment for patients with PCD/KS-associated infertility.

Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder resulting from the loss of normal ciliary function. Symptoms include neonatal respiratory distress, chronic sinusitis, bronchiectasis, situs inversus, and infertility. However, only 15 PCD-associated genes have been identified to cause male infertility to date. Owing to the genetic heterogeneity of PCD, comprehensive molecular genetic testing is not considered the standard of care. Here, we provide an update of the progress on the identification of genetic factors related to PCD associated with male infertility, summarizing the underlying molecular mechanisms, and discuss the clinical implications of these findings. Further research in this field will impact the diagnostic strategy for male infertility, enabling clinicians to provide patients with informed genetic counseling, and help to adopt the best course of treatment for developing directly targeted personalized medicine.

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.

Dear Editor, True hermaphroditism is a condition in which the gonads, genital morphology, and sexuality simultaneously show both male and female characteristics （ovaries and testes） or in which both types of gonadal tissue exist in a single gonad （known as an ovariotestis）. True hermaphroditism associated with a chimeric or 46, XX/46, XY karyotype is extremely rare, and the genitalia of those affected can be characterized as female, male, or mixed.1-3 The cause of true hermaphroditism has not been determined because the condition is relatively rare and has a diverse phenotype.4

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. This study identified two novel variants of the intraflagellar transport protein 140 homolog (IFT140) in the pedigree of a 27-year-old infertile man, the compound heterozygous mutation of which caused male infertility as a result of spermatogenic dysfunction. The patient’s sperm manifested severe oligozoospermia, asthenozoospermia, teratozoospermia, and lack of IFT140 protein expression.

The ejaculate was fully liquefied in 20 min, and a semen analysis was performed in our laboratory according to the standard World Health Organization (WHO) criteria. Author Contributions YWS collected and provided all the clinic information; QZ wrote the paper; LD and PL participated in the collection of the specimens and helped to draft the manuscript and subsequently review the manuscript. Turner RM, Foster JA, Gerton GL, Moss SB, Patrizio P. Molecular evaluation of two major human sperm fibrous sheath proteins, pro-hAKAP82 and hAKAP82, in stump tail sperm.

[3] A study on 18 individual cases found that 11 patients (61.1%) had a homozygous deletion of a 200-kb fragment of the DPY19L gene, two (11.1%) had a homozygous nonsynonymous mutation in exon 8 (p.R298C), one (5.6%) had a homozygous new splice site mutation at the junction of exon-intron 16 (c.1579_1580 + 4delAGGTAAinsTCAT), and four (22.2%) had no mutations in DPY19L2, SPATA16, or PICK1. Studies have indicated that the product of the DPY19L2 gene stabilizes acrosomes, allows the anchoring of the acroplaxome to the nuclear membrane, and mediates the formation of normal sperm morphology, eventually promoting sperm head elongation and acrosome formation. Author Contributions LKZ, ZYJ, and RHT collected and provided all the clinic information; YWS wrote the manuscript; LBM, QZ, and LD carried out all the related examinations; PL designed the study, supervised the data collection and examinations, and reviewed the paper.

No spermatozoa were observed in either sample before or after centrifugation, so the patient was diagnosed as azoospermic according to the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen (2010). Cell proliferation was observed in the seminiferous tubule, but the numbers of spermatogenic cells were reduced from normal, and no mature spermatozoa were observed. [...]the basement membrane showed thickening with hyaline degeneration. For patients seeking treatment for fertility problems, advice on the use of donor semen for assisted reproduction or adoption should not be excluded if long-term reproductive function of the male patient is not satisfactory.

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.