Related Experiment Video
Updated: May 22, 2026
Mouse Round Spermatid Injection
Published on: January 26, 2024
Mice expressing aberrant sperm-specific protein PMIS2 produce normal-looking but fertilization-incompetent
Ryo Yamaguchi1, Yoshitaka Fujihara, Masahito Ikawa
1Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Abstract:
Eight kinds of gene-disrupted mice (Clgn, Calr3, Pdilt, Tpst2, Ace, Adam1a, Adam2, and Adam3) show impaired sperm transition into the oviducts and defective sperm binding to the zona pellucida. All of these knockout strains are reported to lack or show aberrant expression of a disintegrin and metallopeptidase domain 3 (ADAM3) on the sperm membrane. We performed proteomic analyses of the proteins of these infertile spermatozoa to clarify whether the abnormal function is caused exclusively by a deficiency in ADAM3 expression. Two proteins, named PMIS1 and PMIS2, were missing in spermatozoa from Clgn-disrupted mice. To study their roles, we generated two gene-disrupted mouse lines. Pmis1-knockout mice were fertile, but Pmis2-knockout males were sterile because of a failure of sperm transport into the oviducts. Pmis2-deficient spermatozoa also failed to bind to the zona pellucida. However, they showed normal fertilizing ability when eggs surrounded with cumulus cells were used for in vitro fertilization. Further analysis revealed that these spermatozoa lacked the ADAM3 protein, but the amount of PMIS2 was also severely reduced in Adam3-deficient spermatozoa. These results suggest that PMIS2 might function both as the ultimate factor regulating sperm transport into the oviducts and in modulating sperm-zona binding.
Insights
Male infertility linked to sperm transport and zona binding issues may stem from PMIS2 deficiency. This protein is crucial for sperm function, impacting fertility in mice by regulating oviductal transport and zona pellucida interaction.
Area of Science:
- Reproductive Biology
- Sperm Physiology
- Molecular Genetics
Background:
- Gene-disrupted mouse models (Clgn, Calr3, Pdilt, Tpst2, Ace, Adam1a, Adam2, Adam3) exhibit impaired sperm transport and zona pellucida binding.
- These knockout strains often display absent or aberrant expression of sperm membrane protein ADAM3 (a disintegrin and metallopeptidase domain 3).
Purpose of the Study:
- To investigate whether impaired sperm function in infertile mice is solely due to ADAM3 deficiency.
- To identify and characterize novel proteins involved in sperm function using proteomic analysis.
Main Methods:
- Proteomic analysis of spermatozoa from infertile gene-disrupted mice.
- Generation and analysis of Pmis1 and Pmis2 gene-disrupted mouse lines.
- In vitro fertilization assays using Pmis2-deficient spermatozoa.
Main Results:
- Proteomic analysis identified PMIS1 and PMIS2 proteins as missing in Clgn-disrupted mouse spermatozoa.
- Pmis2-knockout male mice were sterile, showing failure in sperm transport into oviducts and defective zona pellucida binding.
- Pmis2-deficient spermatozoa exhibited normal fertilization in vitro when cumulus cells were present.
- Adam3-deficient spermatozoa lacked ADAM3 protein, and PMIS2 levels were also significantly reduced.
Conclusions:
- PMIS2 plays a critical role in regulating sperm transport into the oviducts.
- PMIS2 is involved in modulating sperm-zona pellucida binding.
- The findings suggest a complex interplay between PMIS2 and ADAM3 in ensuring male fertility.
