Introduction:
Globozoospermia is a rare genetic disorder that can contribute to infertility in males. Infertility can be traumatic for couples who are trying hard to conceive. Various factors can contribute to infertility; however, globozoospermia is considered a very rare cause. Still, it is an impactful condition that significantly hampers male fertility. The main characteristic feature of this condition is the presence of round-headed spermatozoa in the absence of acrosomes. This article aims to explain globozoospermia, exploring its symptoms, causes, diagnosis, and treatment.
What Is Globozoospermia?
Globozoospermia is a rare genetic condition that affects only males. It is a very rare condition, affecting only less than 0.1 percent of male infertility. However, it has a great impact on male infertility. This condition is characterized by abnormal sperm with round-headed spermatozoa without acrosomes, a cap-like structure found on the tip of a spermatozoon that releases enzymes when the sperm contacts the ovum, making fusion possible with the ovum in the sexual reproductive process. Because of the absence of acrosomes, it can lead to an inability to father biological children.
In general, the morphology of a normal sperm cell has an oval-shaped head with a covering called the acrosome that contains enzymes to destroy the outer membrane of an egg cell for easy penetration of the sperm into the egg for fertilization. In the case of globozoospermia, the sperm cells have a round head without an acrosome. Hence, the penetration into the egg cells cannot fertilize an egg cell, leading to infertility.
Males affected by this condition may suffer from reduced fertility or infertility. Researchers suggest that globozoospermia can occur as a total globozoospermia, where the complete sperm cells will be round-headed without acrosomes, or as a partial globozoospermia, where around 20 to 60 percent of the sperm is round-headed without acrosomes, along with some normal sperm also identified in the sperm count. However, it is not well known whether these two forms are different types of the same syndrome or different syndromes.
What Are the Types of Globozoospermia?
Globozoospermia is classified into two types:
-
Type 1 - In this type, a complete lack of acrosomes is noted, along with the absence of acrosomal enzymes and the spherical arrangement of the chromatin. As all the significant structures in sperm are absent, it is impossible to penetrate the egg.
-
Type 2 - In this type of globozoospermia, a few acrosomal covers are surrounded by cytoplasmic material, suggesting secondary degenerative changes. In this type, a conical nucleus is also present. Research suggests that infertility occurs in this type of globozoospermia due to abnormal chromatin packaging, preventing proper fertilization.
What Are the Causes of Globozoospermia?
Globozoospermia is a genetic disorder most commonly caused by variations in the DPY19L2 gene. This genetic mutation is found in about 70 percent of men with globozoospermia. Mutations in other genes, such as PICK1 and SPATA16, can also cause globozoospermia.
The DPY19L2 gene provides information for producing a protein required in developing sperm cells. The role of the DPY19L2 protein is to develop the acrosome and the sperm head elongation, which are the main steps in sperm cell maturation. Any variations occurring in the DPY19L2 gene can cause functional loss of the DPY19L2 protein, resulting in sperm cells with no acrosome and no elongation in the sperm head.
The absence of an acrosome gives rise to abnormal sperm that are unable to get through an egg cell to fertilize it, resulting in infertility in affected men. Researchers have also described other characteristics of the abnormal sperm cells occurring in the DPY19L2 gene mutation that make fertilization of an egg cell difficult. However, the exact reason why the changes in the DPY19L2 gene are involved in the formation of these characteristics is still unclear.
Other genes responsible for globozoospermia include PICK1 and SPATA16. Mutation in PICK1 (protein kinase C) can result in defects in proacrosomal vesicles merging, which are responsible for acrosomal formation. Defects in proacrosomal vesicles can result in round-headed sperm formation, making the sperm unable to bind to the egg and leading to infertility. SPATA 16 (spermatogenesis-associated protein) plays an essential role in acrosome formation and spermatogenesis. Mutation in this gene can give rise to round-headed sperm due to acrosome absence, making it unable to penetrate the gene and leading to infertility in males.
What Are the Symptoms of Globozoospermia?
The main symptom of this condition manifests as male infertility. They may not be able to achieve pregnancy even with regular, unprotected intercourse. Apart from the effect on fertility, individuals with globozoospermia do not exhibit any other symptoms. Individuals with globozoospermia have normal physical and mental development, hormonal profiles, and clinical features.
How Is Globozoospermia Diagnosed?
The diagnosis of globozoospermia generally involves a complete patient evaluation, including a physical examination, medical history, family history, and a few laboratory tests. The main laboratory test conducted is semen analysis. During this test, a semen sample is collected and checked for various parameters, including sperm morphology, count, motility, and the presence of acrosomes. In people with globozoospermia, the main characteristic of round-headed sperm lacking acrosomes will be revealed in the sperm analysis, confirming the diagnosis. Some individuals with globozoospermia may also show other signs of impaired sperm function, like reduced sperm count and sperm motility.
In some cases, genetic testing may be conducted to understand the underlying genetic abnormalities contributing to globozoospermia. Genetic testing, including targeted gene sequencing and karyotype analysis, will help identify specific mutations associated with the condition.
What Is the Treatment for Globozoospermia?
Individuals with globozoospermia will require assisted reproduction techniques (ART) to conceive a baby with their partner using their sperm. Intracytoplasmic injection (ICSI) is used to perform fertilization in individuals with this condition. In this technique, each sperm will be injected into each egg, keeping out the function of the acrosome, by which fertilization can still be achieved. In some cases, if the globozoospermia sperm cannot activate the egg independently, calcium ionophore treatment is used to activate the egg artificially; thereby, fertilization can be achieved.
Conclusion:
Globozoospermia is a genetic condition that can significantly impact male fertility. The exact cause of globozoospermia is not completely understood. However, a mutation in the DPY19L2 gene is the primary reason for this condition. The affected individual is physically and mentally normal and only faces fertility issues. With advancements in the medical field, globozoospermia can be treated effectively with assisted reproduction techniques, making the big dream of parenting possible.
