Fig. 1: Oligoasthenoteratozoospermia and axonemal defects in spermatozoa associated with human CEP112 variants. | Nature Communications

Fig. 1: Oligoasthenoteratozoospermia and axonemal defects in spermatozoa associated with human CEP112 variants.

From: CEP112 coordinates translational regulation of essential fertility genes during spermiogenesis through phase separation in humans and mice

Fig. 1

a Pedigrees and Sanger sequencing confirmation of bi-allelic CEP112 variants in two unrelated men with oligoasthenoteratozoospermia (F1-Y3937 and F2-Y9438). Affected individuals: filled symbols; unaffected: open symbols. Probands screened by whole-exome sequencing (WES): black arrows. Sanger sequencing was performed on numbered individuals to validate the variants. C: control. b Schematic representation of the CEP112 protein structure and location of identified variants. Domains are indicated by colored rectangles: DUF4485 (red) and coiled-coil regions (purple). Patient mutations discovered in this study are shown in red (c.226C>T p.R76X, c.268G>A p.G90R, c.410C>T p.S137L, c.2297A>G p.H766R), while previously reported variants associated with acephalic spermatozoa syndrome are shown in black (c.496C>T p.R166X, c.2074C>T p.R692W, c.2104C>T p.R702C) above the protein structure. The genomic structure of CEP112 is shown below the protein diagram, with exons represented by vertical lines. c Conservation of the missense-mutated amino acids is indicated by the alignment of nine species. The detected missense variants were conserved according to the sequence alignment. Morphological assessment of spermatozoa from a fertile control and CEP112-deficient probands using Papanicolaou staining (d) and scanning electron microscopy (SEM) (e). Spermatozoa from the control exhibit normal morphology with elongated, smooth flagella. In contrast, spermatozoa from probands display a range of head and flagellar abnormalities (Scale bar: 5 μm). f Transmission electron microscopy (TEM) reveals ultrastructural defects in sperm flagella of CEP112-deficient individuals. Cross-sections of control spermatozoa show the canonical “9 + 2” axonemal structure. Spermatozoa from probands exhibit loss of central pair (CP) microtubules (“9 + 0” configuration), disorganization of the “9 + 2” structure, and disordered outer dense fibers (ODFs) in the midpiece. Principal and end piece sections display missing or disorganized central and peripheral microtubules, as well as incomplete fibrous sheaths (Scale bar: 100 nm). g Aberrant ultrastructure of the connecting piece in spermatozoa from CEP112-deficient probands revealed by TEM. Proximal centrioles (PCs) and distal centrioles (DCs) are missing or incomplete in the connecting piece of affected individuals (Scale bar: 100 nm). Experiments were repeated three times independently with similar results; representative images are shown in d–g.

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