Macrozoospermia associated with mutations of AURKC gene: first case report in Latin America and literature review / Macrozoospermia asociada con mutaciones del gen AURKC: primer caso clínico en Latinoamérica y revisión de la bibliografía

A Chilean 35-year-old male patient with a history of primary infertility made an appointment at the Unit of Reproductive Medicine at Clínica Las Condes, Santiago, Chile. Multiple semen analyses revealed abnormal sperm morphology as the most prevalent finding. Multiflagellated and macrocephalic spermatozoa were observed and indicated a possible macrozoospermic phenotype. The constant presence of abnormal sperm morphology led the scope of the study to include Aurora Kinase C (AURKC) gene sequencing. The patient was diagnosed with a homozygous mutation of this gene. The mutation was detected in exon 6, type c.744C>G+/+ (P.Y248*) variant. As previously described in the Human Gene Mutation Database (HGMD), this pathogenic variant is associated with macrozoospermia. Although this mutation is not the most frequently observed, it is the first of its kind reported in Latin America

Un chileno de 35 años con antecedentes de infertilidad primaria consultó en la Unidad de Medicina Reproductiva de la Clínica Las Condes, Santiago, Chile. Múltiples espermiogramas revelaron una morfología anormal de los espermatozoides como la anomalía más relevante. Se observaban espermatozoides multiflagelados y macrocefálicos, lo que indicaba un fenotipo de macrozoospermia. La uniformidad del patrón observado condujo a ampliar el enfoque del estudio hacia la secuenciación del gen cinasa Aurora C (AURKC). Al paciente se le diagnosticó una mutación homocigota de este gen. La mutación fue detectada en el exón 6, con la variante c.744C>G+/+ (P.Y248*). Como se ha descrito anteriormente en la Base de Datos de Mutaciones de Genes Humanos (HGMD), esta variante patogénica se asocia a macrozoospermia. Aunque esta mutación no es la que se observa con más frecuencia, es la primera de su tipo notificada en Latinoamérica

Macrozoospermia associated with mutations of AURKC gene: First case report in Latin America and literature review.

A Chilean 35-year-old male patient with a history of primary infertility made an appointment at the Unit of Reproductive Medicine at Clínica Las Condes, Santiago, Chile. Multiple semen analyses revealed abnormal sperm morphology as the most prevalent finding. Multiflagellated and macrocephalic spermatozoa were observed and indicated a possible macrozoospermic phenotype. The constant presence of abnormal sperm morphology led the scope of the study to include Aurora Kinase C (AURKC) gene sequencing. The patient was diagnosed with a homozygous mutation of this gene. The mutation was detected in exon 6, type c.744C>G+/+ (P.Y248*) variant. As previously described in the Human Gene Mutation Database (HGMD), this pathogenic variant is associated with macrozoospermia. Although this mutation is not the most frequently observed, it is the first of its kind reported in Latin America.

Soluble Delta-like ligand 1 alters human endometrial epithelial cell adhesive capacity.

The endometrium undergoes substantial morphological and functional changes to become receptive to embryo implantation and to enable establishment of a successful pregnancy. Reduced Delta-like ligand 1 (DLL1, Notch ligand) in the endometrium is associated with infertility. DLL1 can be cleaved by 'a disintegrin and metalloprotease' (ADAM) proteases to produce a soluble ligand that may act to inhibit Notch signalling. We used an enzyme-linked immunosorbent assay to quantify soluble DLL1 in uterine lavages from fertile and infertile women in the secretory phase of the menstrual cycle. We also determined the cellular location and immunostaining intensity of ADAM12 and 17 in human endometrium throughout the cycle. Functional effects of soluble DLL1 in receptivity were analysed using in vitro adhesion and proliferation assays and gene expression analysis of Notch signalling targets. Soluble DLL1 was significantly increased in uterine lavage samples of infertile women compared with fertile women in the secretory phase of the menstrual cycle. This coincided with significantly increased ADAM17 immunostaining detected in the endometrial luminal epithelium in the mid-secretory phase in infertile women. Soluble DLL1 significantly inhibited the adhesive capacity of endometrial epithelial cells via downregulation of helix-loop-helix and hairy/enhancer of split family member HES1 mRNA. Thus, soluble DLL1 may serve as a suitable target or potential biomarker for receptivity.