MSGID: 1:317/3 643e1ce5   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    New genetic target for male contraception identified    
      
     Date:   
         April 17, 2023   
     Source:   
         Washington State University   
     Summary:   
         Discovery of a gene in multiple mammalian species could pave the   
         way for a highly effective, reversible and non-hormonal male   
         contraceptive for humans and animals. Researchers identified   
         expression of the gene, Arrdc5, in the testicular tissue of mice,   
         pigs, cattle and humans. When they knocked out the gene in mice,   
         it created infertility only in the males, impacting their sperm   
         count, movement and shape.   
      
      
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   FULL STORY   
   ==========================================================================   
   Discovery of a gene in multiple mammalian species could pave the way   
   for a highly effective, reversible and non-hormonal male contraceptive   
   for humans and animals.   
      
      
   ==========================================================================   
   Washington State University researchers identified expression of the gene,   
   Arrdc5, in the testicular tissue of mice, pigs, cattle and humans. When   
   they knocked out the gene in mice, it created infertility only in the   
   males, impacting their sperm count, movement and shape. The researchers   
   detailed their findings in the journal Nature Communications.   
      
   "The study identifies this gene for the first time as being expressed   
   only in testicular tissue, nowhere else in the body, and it's expressed by   
   multiple mammalian species," said Jon Oatley, senior author and professor   
   in WSU's School of Molecular Biosciences. "When this gene is inactivated   
   or inhibited in males, they make sperm that cannot fertilize an egg, and   
   that's a prime target for male contraceptive development."  While other   
   molecular targets have been identified for potential male contraceptive   
   development, the Arrdc5 gene is specific to the male testes and found in   
   multiple species. Importantly, lack of the gene also causes significant   
   infertility creating a condition called oligoasthenoteratospermia or   
   OAT. This condition, the most common diagnosis for human male infertility,   
   shows a decrease in the amount of sperm produced, slowed mobility and   
   distorted shape so that the sperm are unable to fuse with an egg.   
      
   In the WSU study, the male mice lacking this gene produced 28% less   
   sperm that moved 2.8 times slower than in normal mice - and about 98%   
   of their sperm had abnormal heads and mid-pieces.   
      
   The study indicates that the protein encoded by this gene is required   
   for normal sperm production. Oatley's team will next work on designing   
   a drug that would inhibit production or function of that protein.   
      
   Disrupting this protein wouldn't require any hormonal interference,   
   a key hurdle in male contraception since testosterone plays other roles   
   beyond sperm production in men including building bone mass and muscle   
   strength as well as red blood cell production. Designing a drug to target   
   this protein would also make it easily reversible as a contraceptive.   
      
   "You don't want to wipe out the ability to ever make sperm - just stop   
   the sperm that are being made from being made correctly," he said. "Then,   
   in theory, you could remove the drug and the sperm would start being built   
   normally again."  Oatley and study first author Mariana Giassetti have   
   filed a provisional patent for the development of a male contraceptive   
   based on this gene and the protein it encodes.   
      
   Because the gene is found across mammalian species, this knowledge   
   also holds promise for use in animals, Oatley said. The team analyzed   
   available biological data on DNA and protein sequences in mammals and   
   found the gene in almost every known mammal species. This opens the   
   potential to develop male contraception for use in livestock, perhaps   
   replacing castration in some instances as a way to control reproduction,   
   and in wildlife when managers seek to limit overpopulation of a species.   
      
   The initial focus, however, is on giving humans more control over their   
   own reproduction. While there are many forms of birth control for women,   
   they are not always effective or widely available, and more than half   
   of pregnancies worldwide are still unintended, according to the United   
   Nations.   
      
   "Developing a way to curb population growth and stop unwanted   
   pregnancies is really important for the future of the human race,"   
   said Oatley. "Right now, we don't really have anything on the male side   
   for contraception other than surgery and only a small percentage of men   
   choose vasectomies. If we can develop this discovery into a solution for   
   contraception, it could have far- ranging impacts."  This study received   
   support from the National Institutes of Health and WSU's Functional   
   Genomics Initiative, a multi-year university investment to support   
   development of genetic technology research.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Fertility # Birth_Control # Pregnancy_and_Childbirth   
                   # Prostate_Cancer   
             o Plants_&_Animals   
                   # Life_Sciences # Mating_and_Breeding # Biotechnology #   
                   Biotechnology_and_Bioengineering   
       * RELATED_TERMS   
             o House_mouse o Computational_genomics o Mouse o Gene_therapy   
             o Tumor_suppressor_gene o Gene o Allele o DNA_microarray   
      
   ==========================================================================   
   Story Source: Materials provided by Washington_State_University. Original   
   written by Sara Zaske. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Mariana I. Giassetti, Deqiang Miao, Nathan C. Law, Melissa   
      J. Oatley,   
         Julie Park, LeeLa D. Robinson, Lisette A. Maddison, Miranda   
         L. Bernhardt, Jon M. Oatley. ARRDC5 expression is conserved in   
         mammalian testes and required for normal sperm morphogenesis. Nature   
         Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-37735-y   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/04/230417142511.htm   
      
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