News | TLE6 Gene Deficiency Affects Sperm Motility and Count in Males
Infertility is a major global challenge with far-reaching physical and psychological effects. In recent years, researchers have found that genetic mutations affecting early embryonic development, oocyte maturation, and fertilization may contribute to infertility. Mutations in genes associated with the subcortical maternal complex (SCMC) are considered an important cause of infertility involving early embryonic development.
The SCMC is essential to embryonic development and cell division. It supports development by maintaining oocyte cytoplasmic structure and recruiting proteins needed for normal embryo formation. The complex contains several proteins, including the key component transducin-like enhancer of split 6 (TLE6). Research shows that TLE6 deficiency impairs SCMC structural integrity, preventing normal embryo division after the two-cell stage and leading to fragmentation and death. Although substantial evidence supports TLE6's role in female infertility, its function in male germ cells remains underexplored.
To address this gap, Dr. Kousuke Kazama of Kanazawa Medical University worked with Dr. Hirofumi Nishizono and Dr. Yuki Miyagoshi to study the effect of TLE6 deficiency on male fertility using a Tle6-deficient mouse model. Using CRISPR-Cas9 gene editing, the team developed a new male mouse model with heterozygous Tle6 deficiency. The findings were published on October 24, 2024, in volume 12 of Frontiers in Cell and Developmental Biology.
Methods and Findings
“We created a heterozygous Tle6-deficient mouse model to study the effects of Tle6 deficiency in male mice. By combining CRISPR-Cas9 embryo gene editing with electroporation, we successfully generated heterozygous Tle6-deficient mice,” Dr. Kazama said. The team paired Tle6-deficient and wild-type (WT) male mice with WT females to identify mating abnormalities. There were no significant differences in mating frequency or offspring number, and embryos fertilized by sperm from Tle6-deficient males developed at a similar rate to those fertilized by WT sperm.
Although Tle6 deficiency was not significantly associated with transmission of genetic characteristics to the next generation, deficient mice had substantially fewer sperm and significantly lower motility. In addition, 57% of sperm had abnormal head structures and 7% had two heads. Suspecting hormonal imbalance, researchers measured hormone levels and found significantly elevated testosterone in the Tle6-deficient mice.
Potential Role of TLE6 in Sperm Function
Immunofluorescence staining showed that TLE6 protein was localized to the sperm midpiece in deficient mice and overlapped with the location of mitochondria. Because mitochondria are central to sperm energy production, this suggests that TLE6 may have an important role in generating sperm energy. Genes associated with fertilization, sperm motility, and sperm structure were also generally upregulated in the testes of Tle6-deficient mice.
Conclusion
The findings further clarify the effects of TLE6 deficiency in male mice and provide new insights into possible mechanisms of male infertility. Dr. Kazama said: “The role of TLE6 in sperm development may differ among species. Further research is needed to explain how Tle6 deficiency causes sperm abnormalities and to explore its clinical relevance in humans.”
Overall, the study offers a new perspective on male infertility and may support future research and advances in assisted reproductive technology.
News | TLE6 Gene Deficiency Affects Sperm Motility and Count in Males
News | TLE6 Gene Deficiency Affects Sperm Motility and Count in Males
Infertility is a major global challenge with far-reaching physical and psychological effects. In recent years, researchers have found that genetic mutations affecting early embryonic development, oocyte maturation, and fertilization may contribute to infertility. Mutations in genes associated with the subcortical maternal complex (SCMC) are considered an important cause of infertility involving early embryonic development.
The SCMC is essential to embryonic development and cell division. It supports development by maintaining oocyte cytoplasmic structure and recruiting proteins needed for normal embryo formation. The complex contains several proteins, including the key component transducin-like enhancer of split 6 (TLE6). Research shows that TLE6 deficiency impairs SCMC structural integrity, preventing normal embryo division after the two-cell stage and leading to fragmentation and death. Although substantial evidence supports TLE6's role in female infertility, its function in male germ cells remains underexplored.
To address this gap, Dr. Kousuke Kazama of Kanazawa Medical University worked with Dr. Hirofumi Nishizono and Dr. Yuki Miyagoshi to study the effect of TLE6 deficiency on male fertility using a Tle6-deficient mouse model. Using CRISPR-Cas9 gene editing, the team developed a new male mouse model with heterozygous Tle6 deficiency. The findings were published on October 24, 2024, in volume 12 of Frontiers in Cell and Developmental Biology.
Methods and Findings
“We created a heterozygous Tle6-deficient mouse model to study the effects of Tle6 deficiency in male mice. By combining CRISPR-Cas9 embryo gene editing with electroporation, we successfully generated heterozygous Tle6-deficient mice,” Dr. Kazama said. The team paired Tle6-deficient and wild-type (WT) male mice with WT females to identify mating abnormalities. There were no significant differences in mating frequency or offspring number, and embryos fertilized by sperm from Tle6-deficient males developed at a similar rate to those fertilized by WT sperm.
Although Tle6 deficiency was not significantly associated with transmission of genetic characteristics to the next generation, deficient mice had substantially fewer sperm and significantly lower motility. In addition, 57% of sperm had abnormal head structures and 7% had two heads. Suspecting hormonal imbalance, researchers measured hormone levels and found significantly elevated testosterone in the Tle6-deficient mice.
Potential Role of TLE6 in Sperm Function
Immunofluorescence staining showed that TLE6 protein was localized to the sperm midpiece in deficient mice and overlapped with the location of mitochondria. Because mitochondria are central to sperm energy production, this suggests that TLE6 may have an important role in generating sperm energy. Genes associated with fertilization, sperm motility, and sperm structure were also generally upregulated in the testes of Tle6-deficient mice.
Conclusion
The findings further clarify the effects of TLE6 deficiency in male mice and provide new insights into possible mechanisms of male infertility. Dr. Kazama said: “The role of TLE6 in sperm development may differ among species. Further research is needed to explain how Tle6 deficiency causes sperm abnormalities and to explore its clinical relevance in humans.”
Overall, the study offers a new perspective on male infertility and may support future research and advances in assisted reproductive technology.
Source:
Collected online