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

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.

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Key information

Conditions

Azoospermia, Nonobstructive Cryptozoospermia Genital Diseases Genital Diseases, Male Infertility Infertility, Male Male Urogenital Diseases Oligospermia Urogenital Diseases

Sex eligibility

All sexes

Study type

Observational

Primary location

The Third Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510150, China

Location status: Recruiting

Location contact

Chen Liao

CONTACT

[email protected]

86+15918822529

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

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

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

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.

Secondary outcomes

Clinical Classification of Idiopathic Non-obstructive Azoospermia or Cryptozoospermia

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

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.

Study contacts

Contact information is provided by the study sponsor or research team.

Chen

CONTACT

[email protected]

86-15918822529

Sponsors and collaborators

Lead sponsor

The Third Affiliated Hospital of Guangzhou Medical University

Other

Registry information

Official study title

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

Acronym: MTND1-INA/C

Important dates

Study start: 2021
Primary completion: 2027
Study completion: 2027
First posted: Jul 9, 2026
Registry last updated: Jul 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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