Measuring Free Radicals in Human Sperm Cells Related to Microbiota and Lifestyle Factors

NCT05514223 | Recruiting DMC

• 1 other identifier: 202100341
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The cause of infertility can be due to a female factor or a male factor. In case of a male factor, it is often due to poor semen quality. However, the cause of poor quality is often unknown. In previous research, infertility problems in men were related to chemical processes in metabolism causing the formation of free radicals. Free radicals are physiological by-products of our body mechanisms. Free radicals are very reactive and can therefore react with a lot of molecules of cells within our body and cause damage. A balance between free radicals, which are also needed for physiological processes in the body, and antioxidants, which defuses the reactive free radicals, is most desirable. However, as stated in literature, there are a lot of factors that can influence extra free radical production, which causes overloading of the system, resulting in damage on cellular level. Free radicals in semen plasma and on the sperm cell could play a role in male infertility. Nonetheless, free radicals are not used as diagnostic markers due to the lack of detection systems, as free radicals are very short-lived. This study aims to introduce a new technique, called diamond magnetometry, to measure free radicals directly on the sperm cell and in serum. Diamond magnetometry involves very small diamond particles as magnetic sensors that engage a reaction with the free radicals on the sperm cell, causing signals that can be measured. To compare local free radical production with systemic free radical production, other diagnostic biomarkers are also measured in serum. It is hypothesized that the composition of seminal microbiome could influence the free radical concentration. Therefore, this study also aims to explore the microbiota composition and see if this has an influence in semen quality and free radical production. At last, this study also want to correlate standard semen parameters (defined by the World Health Organisation), lifestyle factors and food intake, to detect a role for lifestyle in the production of free radicals.

Conditions

Infertility, Male; Infertility

Keywords

Free radicals; Reactive oxygen species; Microbiota; Diet; Dietary patterns; Fertility; Semen analysis; Fertility clinics; Diamond magnetometry; Lifestyle; Semen; Oxidative stress; Food frequency questionnaire

Outcome Measures

Primary Outcomes (5)

• Free radical concentration in seminal plasma

  Free radical concentration (in mola) in seminal plasma from males of couples visiting the Center of Reproductive Medicine (CRM) of the University Medical Center Groningen (UMCG) is measured using Diamond magnetometry.

  Within 4 hours after production of semen at baseline

• Determination of seminal microbiome species and their abundance in seminal plasma

  The different species and their relative and absolute abundance in seminal microbiota is determined in seminal plasma using qPCR and 16S rRNA sequencing methods (%).

  Baseline

• Free radical concentration in serum using Diamond magnetometry

  Free radical concentration (in mola) in blood serum from males of couples visiting the Center of Reproductive Medicine (CRM) of the University Medical Center Groningen (UMCG) is measured using Diamond magnetometry.

  Within 2 hours of withdrawal at baseline

• Free thiol levels in serum using the Ellman technique

  Free thiol levels in blood serum (in umol/L) from males of couples visiting the Center of Reproductive Medicine (CRM) of the University Medical Center Groningen (UMCG) is measured using the Ellman technique.

  Baseline

• Malondialdehyde levels in serum using the TBARS assay

  Malondialdehyde levels blood serum (in uM) from males of couples visiting the Center of Reproductive Medicine (CRM) of the University Medical Center Groningen (UMCG) is measured using the TBARS assay.

  Baseline

Secondary Outcomes (14)

• Relation between concentration of free radicals in semen and the microbiota species composition in seminal plasma

  Through study completion, an average of 1 year

• Relation between free radical concentration in seminal plasma and free radical concentration in blood serum.

  Through study completion, an average of 1 year

• Relation between free radical concentration in seminal plasma and free thiol levels in blood serum.

  Through study completion, an average of 1 year

• Relation between free radical concentration in seminal plasma and concentration of Malondialdehyde in blood serum.

  Through study completion, an average of 1 year

• Relation between primary objectives (1-5) and seminal volume measured according to the WHO guidelines.

  Through study completion, an average of 1 year

Study Arms (1)

Males of couples seeking fertility treatment

The study population will consist of males of couples that visit the Center reproductive Medicine of the UMCG where a semen analysis is planned for clinical purposes.

Other: Biomaterial collection for observational purpose

Interventions

Biomaterial collection for observational purpose OTHER

The semen will be collected to measure the free radical concentration in seminal plasma and sperm together with the diversity of microbiota. Both males with a normal semen analysis (SA) and abnormal SA according to the WHO guidelines (2010) will be included. Blood plasma will be collected to measure systemic radical concentration and all outcomes will be related to lifestyle factors and food intake acquired through hospital charts and routinely conducted questionnaires together with a food frequency Questionnaire (FFQ).

Males of couples seeking fertility treatment

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Males of couples visiting the CRM of the UMCG

You may qualify if:

• Males of couples visiting the CRM at the UMCG between 18-55 years old.
• Planned semen-analysis as standard care.

You may not qualify if:

• Males who receive(d) chemo- and/or radiotherapy, use(d) testosterone suppletion and/or anabolic steroids
• Males who are azoospermic
• Males who have an abnormal SA due to genetic causes.
• Semen analysis with round cells \>2x106 /ml (as marker for infection)
• Males who currently use antibiotics

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Centre Groningen

Groningen, 9713GZ, Netherlands

RECRUITING

Related Publications (14)

• Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci. 2015 Oct-Dec;8(4):191-6. doi: 10.4103/0974-1208.170370.

  PMID: 26752853 BACKGROUND

• Tomaiuolo R, Veneruso I, Cariati F, D'Argenio V. Microbiota and Human Reproduction: The Case of Female Infertility. High Throughput. 2020 May 3;9(2):12. doi: 10.3390/ht9020012.

  PMID: 32375241 BACKGROUND

• Mamin HJ, Kim M, Sherwood MH, Rettner CT, Ohno K, Awschalom DD, Rugar D. Nanoscale nuclear magnetic resonance with a nitrogen-vacancy spin sensor. Science. 2013 Feb 1;339(6119):557-60. doi: 10.1126/science.1231540.

  PMID: 23372008 BACKGROUND

• Baud D, Pattaroni C, Vulliemoz N, Castella V, Marsland BJ, Stojanov M. Sperm Microbiota and Its Impact on Semen Parameters. Front Microbiol. 2019 Feb 12;10:234. doi: 10.3389/fmicb.2019.00234. eCollection 2019.

  PMID: 30809218 BACKGROUND

• Weng SL, Chiu CM, Lin FM, Huang WC, Liang C, Yang T, Yang TL, Liu CY, Wu WY, Chang YA, Chang TH, Huang HD. Bacterial communities in semen from men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota to semen quality. PLoS One. 2014 Oct 23;9(10):e110152. doi: 10.1371/journal.pone.0110152. eCollection 2014.

  PMID: 25340531 BACKGROUND

• Thoma ME, McLain AC, Louis JF, King RB, Trumble AC, Sundaram R, Buck Louis GM. Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil Steril. 2013 Apr;99(5):1324-1331.e1. doi: 10.1016/j.fertnstert.2012.11.037. Epub 2013 Jan 3.

  PMID: 23290741 BACKGROUND

• Hou D, Zhou X, Zhong X, Settles ML, Herring J, Wang L, Abdo Z, Forney LJ, Xu C. Microbiota of the seminal fluid from healthy and infertile men. Fertil Steril. 2013 Nov;100(5):1261-9. doi: 10.1016/j.fertnstert.2013.07.1991. Epub 2013 Aug 29.

  PMID: 23993888 BACKGROUND

• Agarwal A, Rana M, Qiu E, AlBunni H, Bui AD, Henkel R. Role of oxidative stress, infection and inflammation in male infertility. Andrologia. 2018 Dec;50(11):e13126. doi: 10.1111/and.13126.

  PMID: 30569652 BACKGROUND

• DiGuiseppi J, Fridovich I. The toxicology of molecular oxygen. Crit Rev Toxicol. 1984;12(4):315-42. doi: 10.3109/10408448409044213.

  PMID: 6204814 BACKGROUND

• Ciobanu L, Seeber DA, Pennington CH. 3D MR microscopy with resolution 3.7 microm by 3.3 microm by 3.3 microm. J Magn Reson. 2002 Sep-Oct;158(1-2):178-82. doi: 10.1016/s1090-7807(02)00071-x.

  PMID: 12419685 BACKGROUND

• Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010 May-Jun;16(3):231-45. doi: 10.1093/humupd/dmp048. Epub 2009 Nov 24.

  PMID: 19934213 BACKGROUND

• Farahani L, Tharakan T, Yap T, Ramsay JW, Jayasena CN, Minhas S. The semen microbiome and its impact on sperm function and male fertility: A systematic review and meta-analysis. Andrology. 2021 Jan;9(1):115-144. doi: 10.1111/andr.12886. Epub 2020 Oct 7.

  PMID: 32794312 BACKGROUND

• Bourgonje AR, Gabriels RY, de Borst MH, Bulthuis MLC, Faber KN, van Goor H, Dijkstra G. Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease. Antioxidants (Basel). 2019 Sep 1;8(9):351. doi: 10.3390/antiox8090351.

  PMID: 31480545 BACKGROUND

• Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med. 1990;9(6):515-40. doi: 10.1016/0891-5849(90)90131-2.

  PMID: 2079232 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Semen (whole ejaculate) and blood plasma

MeSH Terms

Conditions

Infertility, Male; Infertility

Condition Hierarchy (Ancestors)

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

Study Officials

• Astrid EP Cantineau

  University Medical Centre Groningen; Centre of Reproductive Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Astrid EP Cantineau, Dr.

CONTACT

+31(0)50-3613032; a.e.p.cantineau@umcg.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: August 24, 2022
• Study Start: June 1, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: July 18, 2024

Record last verified: 2024-07

Locations

NL (1)