Maternal Inheritance of a Pathogenic MT-ND1 Mutation Causes Mitochondrial Dysfunction and Spermatogenic Failure in Men

The Third Affiliated Hospital of Guangzhou Medical University1,200 enrolled

Overview

Idiopathic non-obstructive azoospermia and cryptozoospermia are severe forms of male infertility in which sperm production is absent or extremely low and the cause is often unknown. This retrospective observational study examined whether mitochondrial DNA variants, particularly the MT-ND1 m.3700G\>A variant, are associated with impaired sperm production in Chinese men. Existing clinical records and available biospecimens from affected men, eligible family members, and fertile controls were analyzed to assess familial inheritance patterns, the frequency of the variant, and its association with infertility phenotypes. No study-related treatment or intervention was provided to human participants.

Study Type

OBSERVATIONAL

Enrollment

1,200

Conditions

Azoospermia, Nonobstructive Cryptozoospermia

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * Men with idiopathic non-obstructive azoospermia or cryptozoospermia. * Male patients undergoing a clinically indicated testicular biopsy, testicular sperm aspiration (TESA), microdissection testicular sperm extraction (micro-TESE), or a related clinical procedure, when residual clinical specimens are available. * Comparison participants with normal spermatogenesis, including men with obstructive azoospermia and men undergoing sperm retrieval or testicular tissue evaluation for clinical reasons. * Selected relatives and spouses of enrolled patients, when needed for genetic segregation analysis and determination of variant origin. Exclusion Criteria: * For the idiopathic non-obstructive azoospermia or cryptozoospermia cohort, azoospermia with an established alternative cause, including chromosomal abnormalities, Y-chromosome microdeletions, testicular tumors, severe trauma, prior radiotherapy or chemotherapy, or confirmed infection. * Incomplete clinical data or inability to obtain informed consent. * Biospecimens that do not meet quality requirements for the planned analyses.

Outcomes

Primary Outcomes

Detection and Familial Segregation of the MT-ND1 m.3700G>A Variant

Detection of the MT-ND1 m.3700G\>A mitochondrial DNA variant by sequencing in available biological samples, with assessment of its distribution and maternal segregation among affected male family members, unaffected relatives, unrelated patients with idiopathic non-obstructive azoospermia or cryptozoospermia, and fertile controls.

Time frame: Baseline (single genetic testing assessment at enrollment)

Secondary Outcomes

Clinical Classification of Idiopathic Non-obstructive Azoospermia or Cryptozoospermia

Affected participants were classified as having idiopathic non-obstructive azoospermia or cryptozoospermia according to the clinical diagnosis recorded after routine semen analyses and standard clinical evaluation.

Time frame: Baseline (single clinical classification based on pre-enrollment clinical records)