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Novel NUP210L Variants Cause Fertilization Failure and Male Infertility in Humans
Keyu Ren1,2, Gan Shen1, Han Ma1,2
1Department of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, China.
Clinical Genetics
|April 29, 2026
Summary
Genetic variants in NUP210L cause male infertility by impairing sperm development and chromatin condensation. This discovery expands understanding of fertilization failure and aids in genetic diagnosis for assisted reproduction.
Area of Science:
- Genetics
- Reproductive Biology
- Molecular Biology
Background:
- Fertilization failure is a significant cause of infertility and impacts assisted reproductive technology (ART) success.
- The genetic factors contributing to fertilization failure are not fully understood.
Purpose of the Study:
- To investigate the genetic basis of fertilization failure in two infertile men with macrozoospermia.
- To identify genetic variants associated with recurrent fertilization failure after intracytoplasmic sperm injection (ICSI).
Main Methods:
- Whole-exome sequencing to identify genetic variants.
- Sanger sequencing for variant confirmation.
- Functional analyses including gene expression, sperm morphology assessment (Papanicolaou staining, SEM, TEM), and immunofluorescence for protamine expression.
Main Results:
- Biallelic variants in NUP210L were identified in both patients.
- Reduced NUP210L expression was observed in patient spermatozoa.
- Sperm morphology defects (enlarged heads, multiple flagella) and impaired chromatin condensation (decreased PRM1/PRM2) were noted.
- NUP210L is expressed in late spermatogenic stages (spermatids).
Conclusions:
- NUP210L deficiency is linked to impaired chromatin condensation and fertilization failure.
- This study expands the genetic causes of male infertility.
- Findings offer insights for genetic diagnosis and clinical management in ART.
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