Sperm Phenotype and Differentially Methylated Regions

NCT05461079 | Completed

• 1 other identifier: RME12072017
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Testicular dysgenesis syndrome (TDS) is known to cause epigenetic abnormalities in spermatozoa. Anogenital distance (AGD) is considered to be a suitable clinical marker of TDS, but the direct link between AGD and epigenetic abnormalities is still missing. Infertile men (n=10) presenting with shortened AGD and a control group of normal semen donors (n=10) with normal AGD will then be asked to provide one semen sample each. Using a flow cytometer and sorter (FACS) their spermatozoa will be sorted into populations of spermatozoa with/without DNA fragmentation or with/without chromatin decondensation. These sorted populations of spermatozoa will then be examined for differences in epigenetic imprinting differences using whole genome expression analysis. Whereas the sorting of spermatozoa will be carried out in Basel, the epigenetic analysis will be carried at the University of Geneva.

Conditions

Infertility, Male

Outcome Measures

Primary Outcomes (1)

• anogenital distance and epigenetics

  number of differentially methylated transposable regulatory sequences in the genome of sorted spermatozoa.

  6 months

Secondary Outcomes (5)

• sperm phenotype 1

  6 months

• sperm phenotype 2

  6 months

• sperm phenotype 3

  6 months

• sperm phenotype 4

  6 months

• sperm phenotype 5

  6 months

Study Arms (2)

subfertile men

10 infertile men with shortened AGD (\< 40 mm)

Diagnostic Test: obtention of up to three semen samples

fertile semen donors

10 fertile semen donors with normal AGD (\>40 mm)

Diagnostic Test: obtention of up to three semen samples

Interventions

obtention of up to three semen samples DIAGNOSTIC_TEST

sorting of spermatozoa with flow cytometry. In the presence of insufficient numbers of spermatozoa after sorting (\<15 mill), up to three semen samples will be collected.

Also known as: conventional semen analysis followed by sorting

fertile semen donors; subfertile men

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: male
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Both the 10 infertile men with shortened AGD and the fertile control men (semen donors) will be recruited and examined in the infertility consultation of the Clinic of Gyn. Endocrinology and Reproductive Medicine.

You may qualify if:

• infertile men with known anogenital distance

You may not qualify if:

• sperm concentration must be more than 15 million/ml to allow appropriate sorting with flow cytometry...

Sponsors & Collaborators

• University of Basel: lead
• University of Geneva, Switzerland: collaborator

Study Sites (1)

Christian De Geyter

Basel, 4031, Switzerland

Location

Biospecimen

Retention: SAMPLES WITH DNA

Spermatozoa sorted with FACS according to two different staining methods: YoPro1 (apoptosis) and CMA3 (histone content). After sorting, we obtained four different groups: 1. YoPro1 positive and 2. YoPro1 negative, CMA3 positive and CMA3 negative. All sorted samples were stored frozen and sent for analysis of whole genome methylation status.

MeSH Terms

Conditions

Infertility, Male

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.med.

Study Record Dates

• First Submitted: December 9, 2017
• First Posted: July 15, 2022
• Study Start: November 1, 2017
• Primary Completion: January 30, 2021
• Study Completion: December 31, 2023
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)