Search

Abstract Background Isolated congenital bilateral absence of vas deferens (iCBAVD) in men results in obstructive azoospermia and is mainly caused by pathogenic variants in cystic fibrosis transmembrane conductance regulator (CFTR) or adhesion G protein‐coupled receptor G2 (ADGRG2). Methods The next‐generation sequencing (NGS) was used to screen the mutations in the proband, and Sanger sequencings were performed to validate the compound heterozygous variant of CFTR in his family members. Protein structure simulation was performed to discover the potential pathological mechanism. Results This study reported novel compound heterozygous CFTR mutations (NM:000492.4, Intron: 5T; c.3965_3969dupTTGGG: p.R1325Gfs*5) in two brothers with obstructive azoospermia. The compound heterozygous CFTR mutations were first screened out by NGS in an infertile male patient who exhibited iCBAVD from a nonconsanguineous Chinese family. Histological analysis of the testicular biopsy from this patient revealed normal spermatogenesis and mature spermatozoa were observed in the seminiferous tubules. Surprisingly, the same compound heterozygous CFTR mutations were also observed in his brothers who also exhibited iCBAVD, with their parents being a heterozygous carrier for the mutations, as verified by Sanger sequencing. Protein structure simulation revealed that these mutations potentially led to impaired ATP‐binding ability of CFTR. Conclusion We identified novel compound heterozygous CFTR mutations in two brothers and summarized the literature regarding CFTR mutation and male infertility. Our study may contribute to the genetic diagnosis of iCBAVD and future genetic counseling.

N-linked glycoproteins are rich in seminal plasma, playing essential roles in supporting sperm function and fertilization process. The alteration of seminal plasma glycans and its correspond glycoproteins may lead to sperm dysfunction and even infertility. In present study, an integrative analysis of glycoproteomic and proteomic was performed to investigate the changes of site-specific glycans and glycoptoteins in seminal plasma of asthenozoospermia. By large scale profiling and quantifying 5,018 intact N- glycopeptides in seminal plasma, we identified 92 intact N- glycopeptides from 34 glycoproteins changed in asthenozoospermia. Especially, fucosylated glycans containing lewis x, lewis y and core fucosylation were significantly up-regulated in asthenozoospermia compared to healthy donors. The up-regulation of fucosylated glycans in seminal plasma may interfere sperm surface compositions and regulation of immune response, which subsequently disrupts sperm function. Three differentiated expression of seminal vesicle-specific glycoproteins (fibronectin, seminogelin-2, and glycodelin) were also detected with fucosylation alteration in seminal plasma of asthenozoospermia. The interpretation of the altered site-specific glycan structures provides data for the diagnosis and etiology analysis of male infertility, as well as providing new insights into the potential therapeutic targets for male infertility. [ABSTRACT FROM AUTHOR]

Manipulating the light polarization properties of gold nanoparticle aggregates can facilitate their applications in sensing and imaging. However, control of the intrinsic light polarization on demand at the nanoscale is hindered by the lack of a fundamental understanding of the structure-dependent plasmon coupling in the aggregates. Here, the polarization properties of intrinsic photoluminescence (PL) and scattering of gold nanoparticle dimers and trimers are studied experimentally and computationally at the single-aggregate level. We find that the PL excitation and emission polarization degrees of the aggregates are highly correlated to the shift of their PL and scattering spectra. The results suggest that the degree of PL polarization is dominated by the strength of the longitudinal plasmon resonance mode arising from the plasmon coupling between the two closest particles in the aggregate. While the PL direction is always along the two most strongly interacting particles in the trimers, changing the arrangement can modify the PL polarization degree. This work provides further insights into the mechanism of the plasmon coupling-induced polarized optical response of aggregated metal nanoparticles and suggests routes to achieve on-demand control of the PL light polarization. This paves the way to using the polarized optical response of plasmonic nanostructures for applications in photonics including sensing and imaging. [ABSTRACT FROM AUTHOR]

Background/Objectives To examine the effect of pre-pregnancy maternal body mass index (BMI) on neonatal weight outcomes of twin infants who were conceived by assisted reproductive technology (ART). Subjects/Methods A 10-year (2006-2015) Chinese sample of 3431 mothers and their twin infants conceived by ART from a retrospective cohort were included. The effects of pre-pregnancy maternal BMI on gestational age and birth weight were assessed by generalized linear model and generalized estimating equation model. Results Compared with a normal weight group, pre-pregnancy maternal underweight was associated with lower birth weight and increased risk of small for gestational age (SGA) in twins conceived by ART (birth weight: difference -59.22 g, 95% CI -93.16 to -25.27 g; SGA: RR 1.25, 95% CI 1.09 to 1.43). Pre-pregnancy maternal obesity was associated with higher birth weight and increased risk of preterm birth (birth weight: difference 65.82 g, 95% CI 10.66 to 120.99 g; preterm birth: RR 1.19, 95% CI 1.03-1.37). A nonlinear relationship between pre-pregnancy maternal BMI and SGA was observed. The risk of SGA decreased with the pre-pregnancy maternal BMI up to the turning point (BMI = 21) (RR 0.90, 95% CI 0.86-0.95). Conclusions Among mothers undergoing ART, pre-pregnancy maternal obesity is associated with higher birth weight and higher risk of preterm birth for twin pregnancy, and pre-pregnancy maternal underweight is associated with lower birth weight and higher risk of SGA. Women preparing for ART should maintain a normal BMI to lower the chances of adverse neonatal outcomes., Author(s): Pengfei Qu [sup.1] [sup.2] [sup.3] , Doudou Zhao [sup.1] [sup.2] , Yang Mi [sup.4] , Shaonong Dang [sup.5] , Juanzi Shi [sup.1] [sup.2] , Wenhao Shi [sup.1] [sup.2] Author [...]

Preimplantation embryo arrest (PREMBA) is a common cause of female infertility and recurrent failure of assisted reproductive technology. However, the genetic basis of PREMBA is largely unrevealed. Here, using whole-exome sequencing data from 606 women experiencing PREMBA compared with 2,813 controls, we performed a population and gene-based burden test and identified a candidate gene, karyopherin subunit [alpha]7 (KPNA7). In vitro studies showed that identified sequence variants reduced KPNA7 protein levels, impaired KPNA7 capacity for binding to its substrate ribosomal L1 domain-containing protein 1 (RSL1D1), and affected KPNA7 nuclear transport activity. Comparison between humans and mice suggested that mouse KPNA2, rather than mouse KPNA7, acts as an essential karyopherin in embryonic development. [Kpna2.sup.-/-] female mice showed embryo arrest due to zygotic genome activation defects, recapitulating the phenotype of human PREMBA. In addition, female mice with an oocyte-specific knockout of Rsl1d1 recapitulated the phenotype of [Kpna2.sup.-/-] mice, demonstrating the vital role of substrate RSL1D1. Finally, complementary RNA (cRNA) microinjection of human KPNA7, but not mouse Kpna7, was able to rescue the embryo arrest phenotype in [Kpna2.sup.-/-] mice, suggesting mouse KPNA2 might be a homologue of human KPNA7. Our findings uncovered a mechanistic understanding for the pathogenesis of PREMBA, which acts by impairing nuclear protein transport, and provide a diagnostic marker for PREMBA patients., Introduction Successful human reproduction requires normal embryonic development. Preimplantation embryo arrest (PREMBA) is a common reason for recurrent failure of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and [...]

Objective: To investigate the reproductive outcomes of balanced reciprocal translocation carriers and evaluate the association between the number of metaphase‐II oocytes retrieved and cumulative live birth rates (LBRs). Methods: This retrospective analysis included 344 preimplantation genetic testing (PGT) for structural rearrangement cycles of 281 couples with balanced reciprocal translocations between January 2018 and January 2021. All patients included in the analysis had either delivered a baby or had used all their embryos after one stimulation cycle. All women were followed up for at least 2 years. Results: After ovarian stimulation and oocyte fertilization, 44.2% of PGT for structural rearrangements cycles achieved a live birth. Carrier's sex and female age did not affect the cumulative LBR of reciprocal translocation carriers. Cumulative LBRs steadily increased with the number of oocytes, reaching 64% when >20 oocytes were retrieved. The cutoff values for achieving at least one live birth were 9.5 metaphase‐II (MII) oocytes and 3.5 biopsied embryos. Conclusion: Couples with reciprocal translocations have lower transferable embryo rates and cumulative LBRs. The MII oocytes retrieved may be a crucial factor for cumulative LBRs. A high ovarian response may further increase cumulative LBRs, but avoidance of ovarian hyperstimulation syndrome or other iatrogenic complications should be considered. Synopsis: The purpose of this study was to evaluate risk factors for reproductive outcomes in reciprocal translocation carriers undergoing PGTSR. [ABSTRACT FROM AUTHOR]

Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).