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Published on: December 28, 2021
Actl7a deficiency in mice leads to male infertility and fertilization failure
Xiaopei Zhou1, Zhenxing Liu1, Weimin Jia1
1Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Abstract:
Mutations in the Actl7a gene have been reported to lead to male infertility; however, the detailed mechanism of this phenomenon remains unknown. In this study, we constructed Actl7a gene knockout (KO) mice and found that Actl7a deficiency led to malformed formation of sperm acrosomes, male infertility, fertilization failure during in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and reduced sperm-zona pellucida (ZP) binding ability. Moreover, we found that the localization of the zona pellucida binding protein (ZPBP) was altered in the sperm of Actl7a homozygous KO male mice, which may affect the sperm-zona pellucida binding ability. ACTL7A and ZPBP could form complex, which may be involved in acrosomal formation. Further studies found that localization and expression of the PLCZ1 protein were abnormal in misshapen sperm, leading to reduced calcium oscillations in oocytes. Herein, we provide more detailed mechanisms underlining Actl7a deficiency and male infertility.
Insights
Actl7a gene deficiency causes male infertility in mice due to defective sperm acrosome formation and impaired zona pellucida binding. This study reveals molecular mechanisms involving ZPBP and PLCZ1 proteins, impacting fertilization success.
Area of Science:
- Reproductive Biology
- Genetics
- Molecular Biology
Background:
- Mutations in the Actl7a gene are linked to male infertility, but the underlying mechanisms are not fully understood.
- Understanding the role of Actl7a is crucial for addressing male reproductive health issues.
Purpose of the Study:
- To elucidate the detailed molecular mechanisms by which Actl7a deficiency leads to male infertility.
- To investigate the impact of Actl7a knockout on sperm function and fertilization.
Main Methods:
- Construction and analysis of Actl7a gene knockout (KO) mice.
- Evaluation of sperm acrosome formation, sperm-zona pellucida (ZP) binding ability, and fertilization rates in vitro.
- Analysis of the localization and interaction of ZPBP and PLCZ1 proteins in Actl7a KO sperm.
Main Results:
- Actl7a deficiency resulted in malformed sperm acrosomes, male infertility, and fertilization failure during in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
- Reduced sperm-zona pellucida (ZP) binding ability was observed in Actl7a KO mice.
- Altered localization of ZPBP and abnormal expression/localization of PLCZ1 were identified in Actl7a KO sperm, affecting oocyte calcium oscillations.
Conclusions:
- Actl7a plays a critical role in sperm acrosome formation and function.
- The interaction between ACTL7A and ZPBP is likely involved in acrosomal development.
- Disruption of Actl7a impacts sperm-zona pellucida binding and fertilization through altered ZPBP and PLCZ1 pathways, providing a mechanistic basis for Actl7a-deficiency-induced male infertility.
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