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Meet Our Researchers:
NICHD grantee Dr. Mary Ann Handel traces the genetics of infertility in mice and men


NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development logo
Dr. Mary Ann Handel speaking in the lab.

Dr. Handel talking with colleague at computer.

Screen splits, transitioning to researcher standing at lab counter on left and seated researcher working with test tube on right. Full screen of researcher standing in front of lab shelves. Researcher working at her computer. Dr. Handel and colleague at computer.
Narrator: When Mary Ann Handel began her freshman year in college, she planned to become a high school English teacher. But a genetics course convinced her to stop reading novels and start reading DNA.

Today, Dr. Handel is an NICHD grantee and a senior scientist at The Jackson Laboratory in Maine, where she studies the genes that drive male fertility and infertility.
Dr. Handel on camera.

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Mary Ann Handel, Ph.D.
   




Karyotype of chromosome pairs, labeled 1 through 22 and X/Y.  


Dr. Handel on camera.                    
















Two researchers standing in the lab working.


Close up of researcher's hands, transferring liquid from tiny tubes. Dr. Handel and researcher sitting in front of computer and talking. Researcher standing at a lab counter working with pipette. Dr. Handel on camera
Dr. Mary Ann Handel: When I am talking to my friends and neighbors I say, "I study how sperm cells get made." And most of them can identify with that. And I tell them I am particularly interested in the genes that control how the male germ cells get made. And the other thing that really drives my passion, this came a little bit later in my career, but I am interested in how the sperm cell precursors undergo the specialized division process that gets the right number of chromosomes into every sperm so that when a sperm unites with an egg, when they join up, we now have the proper number of chromosomes, one member of each chromosome pair from each parent.

I study male infertility in the laboratory mouse because we understand the genetics of the laboratory mouse very well. And the genetic pathways that lead to both health and disease in the laboratory mouse are very similar, if not identical, to the pathways that lead to the same healthy or diseased conditions in humans. And so the laboratory mouse is a very amenable organism for study of something like male infertility. And we have all of the advantages of the kinds of genetic engineering that we can do in the mouse so we can create mutations or we can knock out genes and study the effect of that.

In our mutagenesis program we determine animals that are infertile in much the same way that people discover they are infertile. And that is, we mate the animals, and if they don't produce any offspring then we bring these animals to what we call our mouse infertility clinics, and we do a lot of the same analyses on these infertile mice that humans have when they go to an infertility clinic. So for instance when males go to an infertility clinic they find out if their sperm count is normal. Do their sperm look normal? Do their sperm have normal motility? 

In our program we have done random mutagenesis and, interestingly enough, we find we get many more "hits" or genes that cause infertility in males than in females.
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Pie chart labeled "Male Only" is filled in 75% and appears with legend: "75%-80% cause male infertility only."

Chart rotates to reveal a small section at the top of the circle. New section is labeled "Male and Female." Legend also appears below first legend, reading, "16% cause male and female infertility."

Pie chart rotates again and remaining section is filled in. "Female Only" label and legend reading "Less than 10% cause female infertility only" appear.
Dr. Handel: So roughly 75 to 80 percent of our mutations cause male infertility only.  




About 16 percent cause male and female infertility.    



And the remaining, which is less than 10 percent, cause female infertility only.
Dr. Handel on camera. Dr. Handel: My hopes for my own research, selfishly, of course, I want to answer the questions that I am passionate about. I want to discover how the homologous chromosomes recognize each other and pair, and I want to understand the signals that set this special cell division in process resulting in eggs and sperm.

I think we are going to make tremendous progress in the next 10 years. I don’t think we are going to unravel it all. We know enough now to know that every problem that we solve opens a Pandora’s box of problems in behind it that we have to solve. But I think we are going to make tremendous progress in the interaction of environment and physiology in reproduction.
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Special Thanks to The Jackson Laboratory
 
Last Updated Date: 06/23/2014
Last Reviewed Date: 06/23/2014
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