Deciphering the Link Between AK9 Deficiency and Asthenozoospermia

Deciphering the Link Between AK9 Deficiency and Asthenozoospermia

Asthenozoospermia (or asthenospermia) is characterized by low sperm motility and is a primary cause of male infertility. Despite this, its genetic mechanisms are still poorly understood. Research undertaken by Yanwei Sha et al. aimed to change this by studying the connection between the enzyme Adenylate kinase 9 (AK9) and asthenozoospermia.

The prevalence of Asthenozoospermia

Infertility affects 15% of couples globally – of these 20 to 30% are due to male factor issues and 19% due to asthenozoospermia. According to The World Health Organization (WHO), asthenozoospermia is diagnosed in cases of less than 40% total sperm motility or less than 32% rapid progressive motility. Complete asthenozoospermia, meaning 100% immotile sperm in the ejaculate is found in 1 in 5000 men. Asthenozoospermia may be caused by genetic defects or by high levels of reactive oxygen species (ROS) in the male reproductive tract.

“Deficiency in AK9 causes asthenozoospermia and male infertility by destabilizing sperm nucleotide homeostasis” is the latest study on the subject which aims to shed further light on the causes of this condition.

AK9 and sperm motility

Published in the eBioMedicine journal, the study identified that a deficiency in AK9, which encodes a type of adenosine kinase functionally involved in cellular nucleotide homeostasis and energy metabolism, can cause asthenospermia. Considering the prevalence of male infertility among the general population, this research adds valuable insight to the issue.

This study recruited 200 men with normal fertility controls and 165 men with idiopathic asthenozoospermia. Of these, five had bi-allelic AK9 mutations and a decreased ability to sustain nucleotide homeostasis. It was found that this specific mutation also inhibits the breakdown of glucose in sperm. Despite this, the study emphasized that AK9 mutations do not compromise sperm structure or the ability of the sperm to fertilize the egg.

The findings show the significance of AK9 in regulating sperm motility. AK9-deficient individuals had reduced adenosine monophosphate (AMP) and adenosine diphosphate (ADP) levels compared to their counterparts with normal parameters.

The researchers also found that the mutations seen in patients significantly altered the three-dimensional structure of the normal AK9/AKD2 protein. A cross reference of these structures against multiple databases showed that these mutations are absent or rare across a sizable global population, suggesting that the AK9 gene is highly conserved.

Treating asthenozoospermia

Since AK9 affects only sperm motility and energy modalities, intracytoplasmic sperm injection (ICSI) emerged as a viable solution for men with this mutation. The study demonstrated successful pregnancies and healthy deliveries in patients with asthenozoospermia who underwent ICSI.

To conclude

This research into the genetic underpinnings of asthenozoospermia uncovers the pivotal role of AK9 in sperm motility and energy modalities. While mutations in the AK9 gene may hinder natural conception, ICSI is a promising treatment option for couples seeking to overcome male infertility.

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