Acephalic spermatozoa is a rare teratozoospermia associated with male infertility. However, the pathogenesis of this disorder remains unclear. Here, we report a 27 years old infertile male from a consanguineous family, who presented with 99% headless sperm in his ejaculate. Electron microscopic and immunofluorescence analysis suggested breakage at the midpiece of the patient's sperm cells. Subsequent whole-exome sequencing analysis identified a homozygous deletion within TSGA10 (c.211delG; p.A71Hfs*12), which resulted in the production of truncated TSGA10 protein. TSGA10 is a testis-specific protein that localized to the midpiece in the spermatozoa of a normal control; however, immunostaining failed to detect TSGA10 protein in the patient's sperm. Western blot analysis also showed complete absence of TSGA10 protein in the patient. One cycle of in vitro fertilization-assisted reproduction was conducted, but pregnancy was not achieved after embryo transfer, possibly due to poor embryo quality. Therefore, we speculate that the presence of rare sequence variants within TSGA10 may be associated with acephalic spermatozoa in humans.

Multiple morphological abnormalities of flagella (MMAF) is one kind of severe teratozoospermia. Gene mutations reported in previous works only revealed the pathogenesis of approximately half of the MMAF cases, and more genetic defects in MMAF need to be explored. In the present study, we performed a genetic analysis on Han Chinese men with MMAF using whole‐exome sequencing. After filtering out the cases with known gene mutations, we identified five novel mutation sites in the DNAH2 gene in three cases from three families. These mutations were validated through Sanger sequencing and absent in all control individuals. In silico analysis revealed that these DNAH2 variations are deleterious. The spermatozoa with DNAH2 mutations showed severely disarranged axonemal structures with mitochondrial sheath defection. The DNAH2 protein level was significantly decreased and inner dynein arms were absent in the spermatozoa of patients. ICSI treatment was performed for two MMAF patients with DNAH2 mutations and the associated couples successfully achieved pregnancy, indicating good nuclear quality of the sperm from the DNAH2 mutant patients. Together, these data suggest that the DNAH2 mutation can cause severe sperm flagella defects that damage sperm motility. These results provide a novel genetic pathogeny for the human MMAF phenotype.

BackgroundMultiple morphological abnormalities of the sperm flagella (MMAF) is a kind of severe teratozoospermia. Patients with the MMAF phenotype are infertile and present aberrant spermatozoa with absent, short, coiled, bent and/or irregular flagella. Mutations in several genes can explain approximately 30%–50% of MMAF cases and more genetic pathogenies need to be explored. SPEF2 was previously demonstrated to play an essential role in sperm tail development in mice and pig. Dysfunctional mutations in SPEF2 impair sperm motility and cause a short-tail phenotype in both animal models.ObjectiveBased on 42 patients with severe infertility and MMAF phenotype, we explored the new genetic cause of human MMAF phenotype.Methods and resultsBy screening gene variants in 42 patients with MMAF using whole exome sequencing, we identified the c. 12delC, c. 1745-2A > G, c. 4102 G > T and c. 4323dupA mutations in the SPEF2 gene from two patients. Both of these mutations are rare and potentially deleterious. Transmission electron microscope (TEM) analysis showed a disrupted axonemal structure with mitochondrial sheath defects in the patients’ spermatozoa. The SPEF2 protein level was significantly decreased in the spermatozoa of the patients revealed by Western blot (WB) and immunofluorescence (IF) analyses.ConclusionOur experimental findings indicate that loss-of-function mutations in the SPEF2 gene can cause the MMAF phenotype in human.

BackgroundTestis-expressed gene 11 (TEX11) is an X-linked gene and essential for meiotic recombination and chromosomal synapsis. TEX11 deficiency causes meiotic arrest and male infertility, and many TEX11 mutations have been found in azoospermic and infertile men.Case presentationThis study reported one novel TEX11 mutation (2653G → T, in exon 29, GenBank accession number, NM_031276) in two brothers with azoospermia. This mutation was firstly screened out by whole-exome sequencing (WES) and further verified by amplifying and sequencing the specific exon 29. Surprisingly, the same exonic missense mutation (W856C) was observed in two brothers but not in their mother. Histological analysis of testicular biopsy from both brothers revealed meiotic arrest and no post-meiotic round spermatids and mature spermatozoa were observed in the seminiferous tubules. TEX11 expression was observed strongly in spermatogonia and weakly in spermatocytes, but not in Sertoli cells and interstitial cells.ConclusionsWe identified one novel TEX11 mutation in two brothers and summarized the literature regarding TEX11 mutations and male infertility. This study and previous literature indicate that TEX11 mutations are closely associated with male infertility, especially azoospermia, although auxiliary clinical analyses are needed to figure out the causes of male infertility.

Our study highlights the added value of CMA compared with karyotyping in evaluation of asymmetric FGR cases diagnosed during the second trimester without sonographic anomalies. © 2016 John Wiley & Sons, Ltd.

In utero exposure to organochlorine pesticides (OCPs) is thought to be potentially harmful to fetal development. We aimed to investigate the associations of maternal and cord serum OCPs levels with infant birth weight in China. In this study, we measured serum levels of 18 OCPs in 81 mother-infant pairs, including DDT, hexachlorocyclohexanes (BHC), hexachlorobenzene (HCB), heptachlors, chlordanes, endosulfan-I, and mirex using a high-resolution-gas-chromatography with high-resolution-mass-spectrometry method. We found that p,p’-DDE and β-BHC had the highest detection rate in both maternal and cord blood serum (97.2% and 96.7%, respectively), followed by HCB (93.0%, 51.7%), p,p’-DDT (88.7%, 36.7%), and p,p’-DDD (83.1%, 60.0%). Among all OCPs, the concentration of p,p’-DDE was the highest (mothers geometric mean (GM): 203.54 ng/g, newborns GM: 116.14 ng/g), followed by HCB (70.62 ng/g, 65.16 ng/g), and β-BHC (67.67 ng/g, 33.39 ng/g). Multiple linear regression analyses showed that each 1 ng/g increment of cord serum p,p’-DDE, total DDT, and β-BHC was associated with a 0.10g, 0.10g, and 0.92g decrease in infant birth weight, respectively, and as the cord serum concentrations of p,p'-DDT, p,p’-DDD, HCB and mirex increased, the infant birth weight was also decreased, although the associations were not statistically significant due to the relatively small sample size. These results suggest that p,p’-DDE, β-BHC, and HCB were the predominant OCPs in the serum of Chinese pregnant women and cord blood of their newborns. Prenatal exposure to DDT, β-BHC, HCB, and mirex were associated with a decrease in birth weight, but these results need validation in larger sample-sized studies.

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