Novel PNLDC1 mutations underlie nonobstructive azoospermia in humans and mice.

PIWI-interacting RNAs (piRNAs) are small regulatory RNAs (21-35 nucleotides) exclusively expressed in germ cells, where they play a critical role in transposable element repression and post-meiotic gene regulation. The poly(A)-specific RNase-like domain-containing 1 (PNLDC1) protein is essential for piRNA maturation, specifically in 3'-end trimming. Disruption of PNLDC1 has been implicated in nonobstructive azoospermia (NOA) and male infertility.

Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility.

Multiple morphological abnormalities of sperm flagella (MMAF) is a severe form of asthenoteratozoospermia, characterized by morphological abnormalities and reduced motility of sperm, causing male infertility. Although approximately 60% of MMAF cases can be explained genetically, the etiology of the remaining cases is unclear. Here, we identified two novel compound heterozygous variants in the gene, dynein axonemal heavy chain 10 ( DNAH10 ), in three patients from two unrelated Pakistani families using whole-exome sequencing (WES), including one compound heterozygous mutation ( DNAH10 : c.

Novel biallelic ADCY10 variants cause asthenozoospermia with excessive residual cytoplasm and hydronephrosis in humans.

Research Question: Could the novel mutations in ADCY10 cause asthenozoospermia and absorptive hypercalciuria in humans, and the potential pathogenesis?

Design: Whole-exome sequencing and Sanger sequencing were conducted to identify potential pathogenic variants in two unrelated Pakistani families. Reverse transcription polymerase chain reaction was utilized to assess the mutation effect on mRNA levels in the patients. Transmission electron microscopy and scanning electron microscopy were performed to examine the sperm flagellar ultrastructure.

Novel homozygous SPAG17 variants cause human male infertility through multiple morphological abnormalities of spermatozoal flagella related to axonemal microtubule doublets.

Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella (MMAF). Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement. Mammalian sperm-associated antigen 17 ( SPAG17 ) encodes a conserved axonemal protein of cilia and flagella, forming part of the C1a projection of the central apparatus, with functions related to ciliary/flagellar motility, skeletal growth, and male fertility.

A novel homozygous splicing mutation in AK7 causes multiple morphological abnormalities of sperm flagella in patients from consanguineous Pakistani families.

Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals.