Two Studies Reveal the Causes of Male Infertility
Mon, April 19, 2021

Two Studies Reveal the Causes of Male Infertility


Around 15% of couples are infertile, according to Mayo Clinic, an American non-profit academic center. When couples are infertile, they will not be able to conceive a child despite having frequent, unprotected sexual intercourse for a year or more. According to Mayo Clinic, male infertility plays a role in over a third of infertile couples. Low sperm production, abnormal sperm function or blockages that prevent sperm from being delivered contribute to male infertility.

Assessing and Examining Men’s Awareness of Factors Associated With Male Infertility (2016)

Overall, 701 men aged 18 to 50 years completed the online survey administered by D. Daumler and colleagues of biomedical and life sciences journal PMC. 88.5% of men considered themselves to be somewhat (33%), very, or extremely knowledgeable (55.4%) about male reproduction and fertility. Only 11.6% said they are slightly or not at all knowledgeable about male reproduction.

91.2% believed that male factors can cause infertility, whereas 8.8% did not believe that it could contribute to infertility. 64.2% were not very concerned, while others were either somewhat concerned (29.1%) or very or extremely concerned (6.7%). The respondents enumerated the following sources of knowledge about men’s fertility: online sources (55.8%), medical professionals (41.5%), written materials (40.9%), TV/radio (30%), friends/family (28.7%), school/university (25.2%), and others (0.4%). Only 21.3% said they have not received information on men’s fertility.

Regarding their preferred method for receiving information about men’s fertility, the respondents answered: medical professionals (65.9%), online sources (58.3%), written materials (29.4%) TV/radio (25.7%), and others (1.2%). 41.8% of respondents said they are not very or not at all interested in learning more about men’s fertility in the future, whereas 42.4% and 15.8% said they are somewhat interested and very or extremely interested, respectively.    

Among respondents who correctly identified each risk factor and health issue correlated with male infertility, long-term use of steroids and sexually transmitted infections were chosen by 77.8% and 74.3% of men, respectively. Cancer treatment and genetic abnormality are correctly identified by 76.6% and 69.8% of respondents, respectively.

Testicular cancer and depression, which were attendant health issues that make men more at risk of being infertile, were identified correctly by 58.5% and 52.9% of respondents, respectively. When the researchers asked open-ended questions, 64.6% listed risk factors, but only 26.1% gave health issues associated with male infertility. Some of the most common risk factors reported by the respondents were smoking (16.5%), alcohol consumption (16.4%), medical conditions (16.1%) and drug usage (13.6%). Meanwhile, the most frequently cited health issues were cancer (8.0%), diabetes (3.1%), erectile dysfunction (2.9%), and depression (2.6%).



Research From Saudi Arabia Uses A “Genomics First” Approach to Study Male Infertility  

Researchers from Saudi Arabia’s King Faisal Specialist Hospital and Research Center found that 33 genes associated with male infertility were identified using a “genomics first” approach to understand the condition, cited Daniel Jacobson of Bio News, a provider of news and commentary on genetics and more. 

Naif Alhathal, MD, and colleagues of Genetics In Medicine, a monthly peer-reviewed medical journal, used exome sequencing for their study. Exome sequencing is a method for sequencing all protein-coding regions of genes in a genome, with the authors utilizing it to create a genetic basis for male infertility among patients. Writing from the journal Genetics In Medicine, the researchers noted, “However, current estimates of the contribution of genetics to male infertility (15 percent) suffer from the lack of comprehensive genomic analysis in large cohorts.'

69 (24.2%) of 285 non-selected sample of infertile male patients were suspected to have displayed a monogenic form of infertility. The researchers said that it resulted from a defect in a single gene. More than 500 genes have already been linked with male infertility in mouse models, implying that the monogenic contribution in humans has been underestimated. Presently, diagnosing the cause of male infertility involves screening the patient for chromosomal aberrations like Y-chromosome micro-deletions that are too small to be seen by karyotype. Unfortunately, this method has a low diagnostic yield, with only 10.5% of patients were identified to have aberrations.

237 of 285 patients in the study had non-obtrusive azoospermia, referring to a man’s inability to make sperm. Hence, no sperm was ejaculated. The remaining 48 patients exhibited severe oligospermia or having a sperm count lower than one million sperm per milliliter.  Dr. Fowzan Alkuraya, the clinical scientist and author of the study told online news organization GenomeWeb, “There are only around 40 genes linked to non-obstructive azoospermia in humans. Thus, our study nearly doubles the genes linked to this phenotype.”

The candidate genes were chosen and verified from compatible mouse models. The genes were also based on their known biological roles in the development of male germ cells. Based on evidence from the mouse models and independent variants in multiple unrelated patients, three of the genes were said to have “strong evidence” on male infertility in humans.  The researchers hoped that the results will encourage other scientists to undertake further studies on dissecting the molecular basis of male infertility and developing future therapies and methods to improve the diagnosis and management of this condition.



Mutations In the M1AP Gene Found to be A Trigger for Male Infertility

M1AP gene mutations were discovered to be a trigger for male infertility, according to Margot J. Wyroll and colleagues of AJHG (The American Journal of Human Genetics), a monthly peer-reviewed scientific journal in the human genetics field, cited Charlott Repschlager of Bio News. M1AP is a meiosis 1 associated protein. The researchers first screened the DNA of 58 men with complete, but unexplained meiotic arrest. Meiotic arrest is defined as the interruption of spermatogenesis or the process of haploid sperm cells developing from germ cells. The authors identified the same homozygous frameshift mutation in M1AP in three unrelated men.

The team then performed DNA sequencing of nearly 2,000 infertile men, identifying four patients from Münster, Germany, five individuals from the same Turkish family, two cases from Portugal and one patient each from Giessen, Germany, Nijmegen, the Netherlands, and Newcastle upon Tyne. All patients had mutations in the M1AP gene. Between the patients, the common phenotype was non-obstructive azoospermia. The authors found that spermatids and a few mature sperm cells were occasionally and rarely observed in the men’s semen, respectively.



Gene sequencing may be used in the genetic diagnosis of infertility among men as there is strong evidence correlating M1AP to male infertility. Further, M1AP mutations appear to be a frequent cause of autosomal recessive male infertility. Professor Frank Tüttelmann, who led the research, said that a better understanding of the genetic causes of male infertility will benefit future treatment.

Since infertile men showed an alleviated sense of guilt, improving genetic counseling will also enhance patients' treatment experience. Professor Tüttelmann, who established the working group “Reproductive Genetics,” concluded, “Hence, sequencing of the M1AP gene will be incorporated as part of routine genetic diagnostics immediately.”

Genes are one of the factors that cause male infertility, though health and lifestyle factors can also trigger infertility. Hopefully, the aforementioned studies can be used to improve genetic counseling, as well as the management and diagnosis of male infertility.