News | Rare Cause of Male Infertility Identified; ICSI May Offer a Treatment Path
In a study published in eBioMedicine, multidisciplinary laboratory analyses identified AK9 gene defects as a rare cause of male infertility. The discovery clarifies a genetic mechanism of male infertility and suggests intracytoplasmic sperm injection (ICSI) as a potential treatment.
Male infertility caused by AK9 defects
AK9 is an enzyme involved in sperm energy metabolism and cellular nucleotide homeostasis, helping maintain sperm motility. In mouse models and human participants, researchers found that AK9 mutations cause a form of male infertility called **asthenozoospermia**, characterized by severely impaired sperm motility that prevents sperm from reaching and fertilizing the egg effectively.
These mutations are lifelong inherited conditions. Encouragingly, the research team found that ICSI could enable men with AK9 mutations to achieve biological parenthood.
Male infertility and asthenozoospermia
Infertility affects about 15% of couples of reproductive age worldwide, with male factors involved in nearly half of cases. Asthenozoospermia is one of the most common causes. Although the sperm may appear normal, poor motility makes it difficult for them to reach and fertilize the egg.
Previous studies have identified several genes associated with asthenozoospermia, including A-kinase anchoring proteins (AKAPs), human tRNAGlu (TTC), and gene families related to cilia and flagella. However, its genetic pathology remains incompletely understood.
Methods and findings
Researchers performed whole-exome sequencing (WES) in 165 Chinese men with asthenozoospermia and found biallelic AK9 mutations in five. These mutations substantially altered the three-dimensional structure of the AK9 protein, disrupting nucleotide homeostasis in sperm.
Mouse-model experiments further confirmed that AK9 mutations impaired sperm motility without changing sperm structure. Although the mutations prevented normal movement, ICSI still led to successful pregnancies and healthy births.
Clinical significance
The study identifies an important role for AK9 in male reproductive health and suggests a new treatment approach for asthenozoospermia. Successful use of ICSI indicates that affected sperm may retain fertilization capacity despite impaired motility, allowing patients to achieve biological parenthood through assisted reproduction.
News | Rare Cause of Male Infertility Identified; ICSI May Offer a Treatment Path
News | Rare Cause of Male Infertility Identified; ICSI May Offer a Treatment Path
In a study published in eBioMedicine, multidisciplinary laboratory analyses identified AK9 gene defects as a rare cause of male infertility. The discovery clarifies a genetic mechanism of male infertility and suggests intracytoplasmic sperm injection (ICSI) as a potential treatment.
Male infertility caused by AK9 defects
AK9 is an enzyme involved in sperm energy metabolism and cellular nucleotide homeostasis, helping maintain sperm motility. In mouse models and human participants, researchers found that AK9 mutations cause a form of male infertility called **asthenozoospermia**, characterized by severely impaired sperm motility that prevents sperm from reaching and fertilizing the egg effectively.
These mutations are lifelong inherited conditions. Encouragingly, the research team found that ICSI could enable men with AK9 mutations to achieve biological parenthood.
Male infertility and asthenozoospermia
Infertility affects about 15% of couples of reproductive age worldwide, with male factors involved in nearly half of cases. Asthenozoospermia is one of the most common causes. Although the sperm may appear normal, poor motility makes it difficult for them to reach and fertilize the egg.
Previous studies have identified several genes associated with asthenozoospermia, including A-kinase anchoring proteins (AKAPs), human tRNAGlu (TTC), and gene families related to cilia and flagella. However, its genetic pathology remains incompletely understood.
Methods and findings
Researchers performed whole-exome sequencing (WES) in 165 Chinese men with asthenozoospermia and found biallelic AK9 mutations in five. These mutations substantially altered the three-dimensional structure of the AK9 protein, disrupting nucleotide homeostasis in sperm.
Mouse-model experiments further confirmed that AK9 mutations impaired sperm motility without changing sperm structure. Although the mutations prevented normal movement, ICSI still led to successful pregnancies and healthy births.
Clinical significance
The study identifies an important role for AK9 in male reproductive health and suggests a new treatment approach for asthenozoospermia. Successful use of ICSI indicates that affected sperm may retain fertilization capacity despite impaired motility, allowing patients to achieve biological parenthood through assisted reproduction.
Source:
Compiled from online sources