Repeated miscarriages may be caused by sperm DNA fragmentation

Author: Zhang Xing, chief physician of Yangzhou Traditional Chinese Medicine Hospital

Reviewer: Chen Yun, Chief Physician, Jiangsu Provincial Hospital of Traditional Chinese Medicine

Mr. Zhang, who is at his childbearing age, has been married to his wife for three years. During this period, his wife has been pregnant twice, but both ended in miscarriage, which made the couple very distressed.

Figure 1 Copyright image, no permission to reprint

The two went to the hospital for a checkup. All indicators of his wife were normal, and Mr. Zhang's sperm count, motility and other routine parameters were also normal, but his sperm DNA fragmentation index exceeded 30%. Hearing this term, Mr. Zhang was confused. What is sperm DNA fragmentation? Is it possible that all his sperm are broken?

1. Is sperm DNA fragmentation really sperm fragmentation?

In recent years, sperm DNA fragmentation detection, as an important supplement to routine semen analysis, has been considered an important indicator for evaluating sperm and predicting fertility.

Sperm DNA fragmentation refers to the damage to the originally intact sperm DNA caused by various harmful factors during the formation process of sperm.

In the initial formation stage of sperm, lysine-based histones are gradually replaced by arginine-rich protamine. Under the action of protamine, chromatin is highly folded and stored in the sperm head to ensure the stability of genetic material. If the conversion of the two is blocked, it will lead to abnormal chromatin packaging and repair defects, causing DNA damage, resulting in single-strand or double-strand breaks in DNA, and thus generating DNA fragments.

The percentage of sperm with DNA fragmentation due to various adverse factors is called "sperm DNA fragmentation index", which is mainly used to evaluate sperm DNA integrity. The sperm DNA fragmentation index reflects the functionality of sperm genetic material, which directly affects the integrity of the fetal chromosome structure and also affects male fertility.

Generally speaking, the sperm DNA fragmentation index of a normal man will not be higher than 15%. If this index exceeds 30%, it means that the male fertility is reduced.

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2. Why does abnormal sperm DNA fragmentation index lead to miscarriage?

The integrity of sperm DNA will affect the motility and fertilization ability of sperm, egg fertilization, embryo morphology and implantation, and may also cause azoospermia in offspring. Moreover, it is a necessary condition for normal egg fertilization, fertilized egg implantation and embryo development, and plays a key role.

Scholars have conducted statistical analysis on the relationship between male sperm DNA damage and female spontaneous abortion, and found that male sperm DNA damage significantly increases the risk of spontaneous abortion in women. In other words, an increase in the male sperm DNA fragmentation index will affect the combination of sperm and egg, leading to abnormalities, thereby affecting the implantation of the fertilized egg and the early development of the embryo, ultimately leading to a corresponding increase in the female pregnancy rate and abortion rate, and even causing repeated abortion.

3. What causes sperm DNA damage?

According to current research, the main reasons for the occurrence or aggravation of sperm DNA damage are:

1. Abnormal chromatin assembly and abnormal sperm apoptosis

Chromatin refers to a rod-shaped body formed by the spiraling of DNA protein fibers during sperm production. It is the carrier of genes. If there is an abnormality in the assembly of chromatin, it will lead to an increase in the number of sperm DNA fragments.

Abnormal chromatin assembly is mainly caused by diseases, drugs and environmental toxins. Among them, varicocele is closely related to the amount of sperm DNA fragmentation.

Relevant research data show that the natural pregnancy rate between couples of patients with varicocele increases after surgery, while the spontaneous abortion rate and the failure rate of assisted reproductive technology decrease. This is largely due to the improvement of sperm DNA damage in patients after surgery, especially for those patients with severe varicocele and sperm DNA damage. The effect is particularly significant.

In addition, studies have shown that sperm DNA damage is closely related to aging, air pollution, smoking, alcoholism, etc. These factors can cause abnormal sperm apoptosis, thereby aggravating the degree of sperm DNA fragmentation.

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2. Sperm’s oxidative stress response is too strong

An appropriate amount of reactive oxygen free radicals can maintain the normal function of sperm. However, too much reactive oxygen free radicals will have an adverse effect on the testicles and sperm. This situation is called "excessive oxidative stress response of sperm", which is also a pathogenesis of male infertility.

Oxidative stress can affect sperm function in many ways. Reactive oxygen free radicals can not only react with cell membranes, weakening sperm motility and fertilization ability, but also react with sperm DNA, causing DNA damage and changing the sperm of future generations, which is the culprit of azoospermia.

The excessive oxidative stress response of sperm is also closely related to the high temperature of the testicles. Therefore, it is not recommended for men to take sauna baths or wear tight pants, and try not to sit for long periods of time.

References

Wu Jian, Li Lipeng. Research progress of sperm DNA fragmentation detection in assisted reproduction[J]. Laboratory Medicine and Clinic, 2020, 17(21): 3216-3220.

[2] Sun Yinghao. Wu Jieping. Urology[M]. Beijing: People's Medical Publishing House, 2019.

[3] Zhao Junzhao. Decoding the Mysteries of Reproductive Medicine[M]. Beijing: People's Medical Publishing House, 2019.