DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia

Abstract

Non-obstructive azoospermia, the absence of sperm in the ejaculate due to disturbed spermatogenesis, represents the most severe form of male infertility. De novo microdeletions of the Y-chromosomal AZFa region are one of few well-established genetic causes for NOA and are routinely analysed in the diagnostic workup of affected men. So far, it is unclear which of the three genes located in the AZFa chromosomal region is indispensible for germ cell maturation. Here we present four different likely pathogenic loss-of-function variants in the AZFa gene DDX3Y identified by analysing exome sequencing data of more than 1,600 infertile men. Three of the patients underwent testicular sperm extraction and revealed the typical AZFa testicular Sertoli cell-only phenotype. One of the variants was proven to be de novo. Consequently, DDX3Y represents the AZFa key spermatogenic factor and screening for variants in DDX3Y should be included in the diagnostic workflow.

Genome-wide DNA methylation, imprinting, and gene expression in human placentas derived from Assisted Reproductive Technology

“…Interestingly, the upregulated genes ZFY, RPS4Y1, PCDH11Y, and DDX3Y in the ICSI placentas locate on chromosome Y and the expressions of them all correlated significantly with each other in ART male placentas, but not in the controls (Supplementary Table 7). Since male infertility was a common reason (44.4%) for the infertility among the analyzed ICSI male samples (Supplementary Table 17) the upregulated genes DDX3Y 46 , ZFY 47 , and PCDH11Y 48 , which all have been associated with male infertility in previous studies, are notable. Furthermore, the ICSI-associated DEGs MAP1B, HBA1, EPHX1, HBB, and HBG2 enriched in response-to-toxic-substance pathway are also interesting (FDR-corrected q-value < 0.05), considering that environmental exposures have been associated with male infertility in previous studies (Supplementary Table 18).…”

Application of Blended Learning to Veterinary Gross Anatomy Practical Sessions: Students’ Perceptions of Their Learning Experience and Academic Outcomes

“…Advances in technology and the application of new pedagogical approaches are modifying university teaching. In recent years, the emergence of COVID-19 has led to a rethinking of the ways of teaching and to the development of new pedagogical approaches seeking to facilitate the Animals 2023, 13, 1666 2 of 14 improvement of students' learning, giving rise to experiences that could then be applied in the post-COVID era [1]. In this context, blended learning (BL) has emerged as a strategy that uses different pedagogical approaches with the aim of modifying some aspects of how students learn to improve their learning experience [2][3][4][5].…”

An Exercise Immune Fitness Test to Unravel Disease Mechanisms—A Proof-of-Concept Heart Failure Study

“…The following supporting information can be downloaded at: , Table S1: Gene ontology information on the 11 genes identified as described in the text; Table S2: Gene ontology information on the six overlapping genes. References [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ] are cited in the Supplementary Materials.…”