Written by Ben Bunting: BA(Hons), PGCert.
Advanced research studies indicate 39 miscarriages per 1000 women aged 15-49 years worldwide. Clearly this is a worrying statistic for many.
In this article we shall cover the following points:
- DNA fragmentation
- ROS in semen
- Y chromosome microdeletions
- Advanced paternal age
- Low testosterone levels in males
- Assisted reproductive technology (ART)
- Effect of obesity
- Environmental factors
Several female factors like uterine abnormalities, chromosomal aberrations, endocrine abnormalities, and structural abnormalities have been under consideration with the study of miscarriages, but recent search analysis confers about male factors that can cause miscarriages.
For example, DNA fragmentation, ROS in semen, microdeletions in chromosomes, paternal age, environmental factors as well as obesity.
During fertilization, gametes of both male and female contribute, first zygote and then the embryo is developed.
Embryo possesses 50% copies of maternal DNA and 50% paternal DNA.
The integrity of DNA is important for the viability of an embryo. In the case of male infertility, usually a paternal copy of DNA defects.
It may lead to chromosomal aberrations causing miscarriage or early death of the fetus.
In the modern era, the use of assisted reproductive technology (ART) due to male infertility has prevailed which is the leading cause of miscarriage.
Specific measures are needed to preserve the integrity of DNA to prevent recurrent miscarriages.
Development of certain therapeutic measures to properly evaluate and reduce rates of miscarriage, it's necessary to point out contributing factors.
Male infertility factors causing miscarriages
Clinical evaluation of couples who have a miscarriage focuses on the following male factors which cause abortion or miscarriage.
DNA fragmentation in sperms
DNA fragmentation is the phenomenon in which strands of DNA separate and break into pieces causing disintegration of its structure. These structural changes in DNA lead to early miscarriage.
Fragmentation of DNA is not only limited to loss of pregnancy but also contributes its role in congenital anomalies and increase rates of prevalence of carcinomas in childhood.
Oocytes from females, get fertilized with damaged or fragmented spermatozoon, which results in a defective genome in the embryo.
The defective genome contains multiple areas of DNA damage which results in lethal consequences like a miscarriage.
Risk factors for DNA damage are:
ROS in semen
Semen has low levels of reactive oxygen species (also called free radicles) normally, which protect from micrograms including bacteria and viruses.
Excessive alcohol intake, smoking, exposure to xenobiotics, viral and bacterial infections lead to infertility usually, because the production of certain metabolites leads to increased production of reactive oxygen species or free radicles.
These free radicles damage sperm DNA, which results in a defective genome and leads to miscarriage eventually.
As the number of free radicals increases, levels of antioxidants decrease and oxidative stress leads to DNA damage.
DNA fragmentation may also occur, torsional stress increases as DNA is condensed and packed into DNA head.
Moreover, smoking also reduces levels of antioxidants in the body and promotes lipid peroxidation leading to increased production of reactive oxygen species (ROS).
Y chromosome microdeletions
Microdeletions is the phenomenon in which multiple genes get deleted from the genome resulting in fatal consequences.
Several investigations suggest that microdeletions on the Y chromosome are an underlying cause of recurrent miscarriage.
Detailed analysis state that the risk of microdeletions increases significantly in assisted reproductive technology (ART).
This technology is used in infertile males or those who have structural anomalies in genitalia. ART causes genetic abnormalities resulting in frequent miscarriages.
Advanced paternal age
A retrospective study of European couples who had miscarriages analyzed the risks of miscarriage.
According to this 2002 study, fertility in men aged >35 years decreases significantly along with a drop in the number of intercourse per week.
But if women conceive, it leads to chromosomal anomalies as well as miscarriage.
It seems that advancing age affects both men and women in respect of pregnancy outcomes.
Low testosterone levels in male
Infertility is usually due to deficiency of certain hormones which play a vital role in the development of sexual characters.
Testosterone and estrogen play a leading role in the production of sperms and their functioning. Reduced levels of testosterone and estrogen cause decreased production of sperms as well as reduced motility.
Testosterone is necessary for spermatogenesis, which is a process of sperm production.
These sperms, which are produced in such circumstances show increased DNA fragmentation and destruction leading to miscarriage.
Assisted reproductive technology (ART)
Sperm DNA damage is associated with poor assisted reproductive treatment (ART), which is usually used for infertile partners.
Outcomes of ART including reduced fertilization rates, embryo quality, pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases have been demonstrated by recent research and analytical studies.
An imbalance between oxidants and antioxidants creates oxidative stress, decreasing the viability of sperm DNA.
Varicocele manifests as enlargement or swelling in the pampiniform plexus of the scrotum. It also leads to infertility because it produces reactive oxygen species (ROS).
Sperms produced by males who have varicocele are increased in number but they possess abnormalities related to chromatin. These abnormalities are due to oxidative stress.
Sperms produced under oxidative stress are of low quality, which leads to DNA damage and fragmentation.
Consequently, the rate of many pregnancy-related issues involving miscarriage increases significantly as per the findings published in a 2018 study.
Effect of obesity
Obesity usually manifests as increased levels of cholesterol in the body, which increases the rate of metabolism.
Increased rate of metabolism and lipid peroxidation produces more free radicles which decrease the viability of sperms.The molecular composition and function of sperms are altered. These alternations in sperm DNA result in miscarriage.
Certain environmental factors like cigarette smoking, alcohol intake, exposure to radiation, pesticides, and xenobiotics are potential risk factors, that induce increased production of free radicles.
These factors significantly reduce fertility in men. Altered quality and quantity of sperms lead to defective DNA of an embryo, contributing towards miscarriage.
As we can see, there are many relating factors of male infertility which can then contribute towards a failed pregnancy.
The stand out contribution towards a miscarriage is sperm irregularities and DNA fragmentation which can be caused by a number of lifestyle issues that can be avoided.
If these are addressed it can then have a positive impact on other problems such as hormone balance.