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Published on: October 13, 2018
Mice lacking the UBC4-testis gene have a delay in postnatal testis development but normal spermatogenesis and
Nathalie Bedard1, Pascal Hingamp, Zhiyu Pang
1Polypeptide Laboratory, Department of Medicine, McGill University, Strathcona Anatomy and Dentistry Bldg., Rm. W315, 3640 University, Montreal, Quebec, Canada.
Abstract:
Activation of ubiquitination occurs during spermatogenesis and is dependent on the induction of isoforms of the UBC4 family of ubiquitin-conjugating enzymes. The UBC4-testis isoform is testis specific, is induced in round spermatids, and demonstrates biochemical functions distinct from a ubiquitously expressed isoform UBC4-1. To explore further the function of UBC4-testis, mice bearing inactivation of this gene were produced. Homozygous (-/-) mice showed normal body growth and fertility. Although testis weight and morphology were normal in testes from adult mice, examination of young mice during the first wave of spermatogenesis revealed that testes were approximately 10% smaller in weight at 40 and 45 days of age but had become normal at 65 days of age. Overall protein content, levels of ubiquitinated proteins, and ubiquitin-conjugating activity did not differ between wild-type and homozygous (-/-) mice. Spermatid number, as well as the motility of spermatozoa isolated from the epididymis, was also normal in homozygous (-/-) mice. To determine whether the germ cells lacking UBC4-testis might be more sensitive to stress, testes from wild-type and knockout mice were exposed to heat stress by implantation in the abdominal cavity. Testes from both strains of mice showed similar rates of degeneration in response to heat. The lack of an obvious phenotype did not appear to be due to induction of other UBC4 isoforms, as shown by two-dimensional gel immunoblotting. Our data indicate that UBC4-testis plays a role in early maturation of the testis and suggest that the many UBC4 isoforms have mixed redundant and specific functions.
Insights
The UBC4-testis gene knockout mice showed normal fertility and sperm quality, indicating its role in early testis maturation rather than overall function. UBC4-testis (ubiquitin-conjugating enzyme) has specific roles alongside redundant functions of other UBC4 isoforms.
Area of Science:
- Reproductive biology
- Molecular genetics
- Biochemistry
Background:
- Ubiquitination is crucial for spermatogenesis, involving UBC4 family ubiquitin-conjugating enzymes.
- The testis-specific UBC4-testis isoform is induced in round spermatids and has distinct biochemical functions compared to UBC4-1.
Purpose of the Study:
- To investigate the in vivo function of the testis-specific UBC4-testis isoform.
- To determine the impact of UBC4-testis gene inactivation on spermatogenesis and male fertility.
Main Methods:
- Generation and analysis of UBC4-testis knockout (UBC4-testis-/-) mice.
- Assessment of body growth, fertility, testis weight and morphology, protein content, ubiquitination levels, and ubiquitin-conjugating activity.
- Evaluation of spermatid number, sperm motility, and response to heat-induced stress.
Main Results:
- UBC4-testis-/- mice exhibited normal body growth, fertility, testis weight, morphology, protein content, and ubiquitination levels.
- Spermatid counts and sperm motility were unaffected in knockout mice.
- Temporary reduction in testis weight observed during early spermatogenesis (40-45 days), normalizing by 65 days.
Conclusions:
- UBC4-testis plays a role in the early maturation of the testis, but its absence does not impair overall fertility or sperm production.
- The study suggests that UBC4 isoforms possess both redundant and specific functions within the complex process of spermatogenesis.
- Germ cells lacking UBC4-testis are not more sensitive to heat stress.
