Saturday, August 25, 2012

BIRTH CONTROL FOR MALES

How long has birth control been in existence?
Good question. 

     Birth control methods have been utilized for thousands of years. In our present times, many safe and effective methods are easily available to us. Trying to choose is not as difficult if you take the time to research and learn about each method.  Have you considered birth control for males?

     Experimental steps toward a male preventive has made leaps and bounds.
     Recently, “…JQ1  successfully inhibited the production of sperm in lab mice.” (http://news.yahoo.com/science-takes-major-step-towards-creating-male-birth-155039405.html)
     This experimental cancer drug, that was being tested on mice, can serve as a hormone-free contraceptive pill for human men.  What is great about the findings as opposed to others is that the effects of JQ₁, were also found to be reversible.
What about when you don’t want to be sterile? 

Say: reversibility. 


     The effects were reversed through the mice by stopping the daily dosages.  Their sperm levels returned to normal. They were then able to fertilize their female partners and produce healthy offspring.
     According to lead researcher, Dr. Martin Matzuk of the Baylor College of Medicine Houston, "We envision that our discoveries can be completely translated to men, providing a novel and efficacious strategy for a male contraceptive.”
     Before these recent research results there was the first time hopes for a reversible male birth control option. This was earlier this year when the Los Angeles Times reported on a gel.  The gel decreased men’s sperm counts with minimal side effects. That gel contained the hormones testosterone and Nesterone (a man-made progestin).  (http://www.huffingtonpost.com/2012/08/16/male-birth-control-jq1-sperm-count_n_1784361.html)
   In a study led by Dr. Martin Matzuk, director of the Center for Drug Discovery at Baylor, and Dr. James Bradner, assistant professor at Harvard Medical School, found that JQ1, inhibited the amount and quality of sperm produced by male mice. Their study was published in August of the journal Cell.  Matzuk stated that, “We found that the JQ1 molecule causes a contraceptive effect in males,”, and he agreed that, “If you stop the drug, there’s complete reversibility.”  (http://www.webpronews.com/male-birth-control-pill-molecule-identified-2012-08)
     JQ1, in the rodents, impacted spermatogenesis via direct inhibition of the testis-specific bromodomain protein, BRDT.

     JQ1 altered sperm production. The blood-testis barrier was breached.  No separation of the  blood vessels and the seminiferous tubules. The male mice in the study mated normally, but were sterile, as the amount and quality of their sperm was low. Small molecules such as JQ1 can be used in pills similar to those used for female contraceptives.

     Matzuk importantly stated, also, that “JQ1 is not the pill for men, because it also binds other members of the bromodomain family”.  The bromodomain member is, BRDT.
    


     Matzuk emphasized the point, “However, the data is proof of principle that BRDT is an excellent target for male contraception and provides us with useful information for future drug development.”

     Members of the BET (bromodomain and extra terminal motif) family of proteins have been shown to be chromatin-interacting regulators of transcription.  In a BRDT experiment, a mutation was generated in the testis-specific mammalian BET gene Brdt (bromodomain, testis-specific) which disrupted spermiogenesis and male sterility.  (http://www.ncbi.nlm.nih.gov/pubmed/22570411) 

     The experimental steps consisted of:
Germ cell separation
RNA purification and microarray analysis
Quantitative real-time PCR
Northern blot hybridization analysis
In situ hybridization
Immunoblot analysis
Immunofluorescence
Flag-BRDT pull down
Co-immunoprecipitation

     FYI:  The stages of sperm production are spermatocytogenesis, spermatidogenesism, and spermiogenesis. 

     During spermiogenesis, the spermatids begin to grow a tail, and develop a thickened mid-piece, where the mitochondria gather and form an axoneme. Spermatid DNA also undergoes packaging, becoming highly condensed. The DNA is packaged firstly with specific nuclear basic proteins, which are subsequently replaced with protamines during spermatid elongation. The resultant tightly packed chromatin is transcriptionally inactive. The Golgi apparatus surrounds the now condensed nucleus, becoming the acrosome. One of the centrioles of the cell elongates to become the tail of the sperm.  Maturation then takes place under the influence of testosterone, which removes the remaining unnecessary cytoplasm and organelles. The excess cytoplasm, known as residual bodies, is phagocytosed by surrounding Sertoli cells in the testes. The resulting spermatozoa are now mature but lack motility, rendering them sterile. The mature spermatozoa are released from the protective Sertoli cells into the lumen of the seminiferous tubule in a process called spermiation.  The non-motile spermatozoa are transported to the epididymis in testicular fluid secreted by the Sertoli cells with the aid of peristaltic contraction. While in the epididymis the spermatozoa gain motility and become capable of fertilization. However, transport of the mature spermatozoa through the remainder of the male reproductive system is achieved via muscle contraction rather than the spermatozoon's recently acquired motility.

     The BRDT role in spermiogenesis, is in chromatin remodeling.  This is one of the most dramatic chromatin remodeling processes. Indeed, during the postmeiotic maturation of male haploid germ cells, or spermiogenesis, histones are replaced by small basic proteins, which in mammals are transition proteins and protamines. (http://www.mendeley.com/research/role-histones-chromatin-remodelling-during-mammalian-spermiogenesis/)

    BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Several transcript variants encoding multiple isoforms have been found for this gene.
     The protein encoded by this gene belongs to the BET protein family. BET proteins have two N-terminal bromodomains and one C-terminal extraterminal domain (ET domain). BET proteins regulate chromatin reorganization via binding to acetylated histones. This gene is thought to play a role in the transcriptional regulation of spermatogenesis. Although referred to as testis-specific bromodomain (Brdt) protein, RT-PCR indicates that this gene is expressed in both mouse oocytes and testes. Alternative splicing results in multiple transcript variants encoding different proteins.

     So, controlling our reproduction is part of being human with intelligence.  We have been participating for quite some time.
     Don’t ask how long.
     To find your options for birth control, you can check at your friendly neighborhood CVS, or Walgreens.  Research online, too. 

     As far as birth control for males, it is in the process of being discovered.  This has to be perfected.  JQ1 is great and gives the reversibility of its potent effects.  Just stop taking the pill. Boom!  Loaded, and lethal!  BRDT is front runner.  This is where the future in drug development is for male contraception.