Addressing the Male Side of the Human Infertility Equation

Recent Penn State graduate Amy Mook interviews Dr. Marta Tomaszkiewicz, Assistant Research Professor of Biology about her innovative research on male infertility.  Marta is particularly interested in understanding the potential of using RNA information and RNA-based technologies to answer important biological questions. She is currently testing the hypothesis that variation in ampliconic gene expression can explain differences in semen characteristics between fertile and infertile men. Her work can be followed at: https://twitter.com/amplicomics

HOST:
Amy Mook, Penn State Alum, Genetics and Developmental Biology

GUEST:
Dr. Marta Tomaszkiewicz, Assistant Research Professor of Biology 

Transcript

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Mark Shriver:

From Penn State’s Center for Human Evolution and Diversity, this is Tracking Traits.

 [THEME MUSIC]

Nina Jablonski: 

Hello and welcome to the seventh episode of the Tracking Traits podcast. I’m Nina Jablonski , co-director of CHED – the Center for Human Evolution and Diversity at Penn State University.

 Mark Shriver:

And I’m Mark Shriver, the other co-director of CHED. Welcome to the podcast. 

Nina:

For today’s episode, recent Penn State graduate Amy Mook returns to the podcast to interview Marta Tomaszkiewicz about her research. 

Mark:

Amy was our very first student interviewer on Tracking Traits, and is just starting a dual master’s of science program in Genetic Counseling and Public Health at the University of Michigan.

Nina:

The subject of Amy’s interview, Marta Tomaszkiewicz is an Assistant Research Professor of Biology at Penn State. Her CHED-sponsored research project involves a whole new approach to the topic of male infertility. This is a really timely topic, because  infertility currently affects 15% of couples worldwide, and based on current information, the rates are projected to rise each year.

Mark:

Marta’s research is really bold and exciting. She’s pushing established boundaries in the worlds of both medicine and biological research. In the medical world, infertility has almost exclusively been addressed in terms of the female reproductive system. The male side of this issue has been largely overlooked. 

Nina: 

It really has, for a long, long time. And on the biological side, Marta is focusing on RNA rather than DNA, which has been really controversial is science. For a long time, RNA was dismissed by mainstream science as this residual, unimportant aspect of biology. But it’s this kind of thinking that is the enemy of scientific progress. And we know this about RNA in particular, because if it hadn’t been for the tireless work of a scientist studying messenger RNA treatment technologies for decades – with almost no support from the scientific establishment – we wouldn’t have been able to create the COVID- vaccines that are making it possible for millions and millions of people to return to a normal life.  

Mark:

Kati Kariko was that scientist who saw something no one else did, and kept pursuing her vision for decades, going against the grain, and the whole world benefitted. Marta is another one of those scientists willing to take risks and try something no one else is doing.

Nina:

She is investigating ampliconic gene families that are located on the Y-chromosome, with the hope of determining which specific sperm phenotypes relate to fertility and infertility. No one to date has taken this kind of genetic approach to this condition, so it truly is evolutionary.

Mark: 

In Amy’s interview, she talks about the importance of taking risks and getting out of your comfort zone as a scientist, and shares some of her own personal journey. 

Nina:

Marta also shares, as just about all our guests do on the Tracking Traits podcast, the importance of her collaborations with others who work in complimentary disciplines, like medicine and statistics.

Mark:

It’s another great conversation.

Nina:

Let’s give a listen. Here’s Amy Mook interviewing Marta Tomaszkiewicz about addressing the male side of the human infertility equation.

[MUSICAL INTERLUDE]

Amy Mook:

Good morning Marta. Thank you so much for joining me on the podcast. I'm really looking forward to learning more about your research and the story of how you got here. Obviously, the Center for Human Evolution Diversity supports interdisciplinary research on the evolution of humans and human diversity and education and outreach on that research. So if you could just get us started by sharing a bit about, what is the broader impact of your research?

Marta Tomaszkiewicz:

Sure. Thank you for having me. I'm really excited to talk to you about my research. So last year in 2020, according to the bulletin of the World Health Organization, infertility was declared a continually ignored global public health issue. And we know that infertility affects around 15% of couples and the infertility rates are predicted to rise annually. We also know that according to the American Society for Reproductive Medicine, male and female factors contribute equally to infertility, yet most studies have been focusing on women's reproductive health alone.

And additionally, sperm counts are declining worldwide, but we don't really know why. So in our Ted study, we propose to bridge this gap by investigating the association between the amount of the products of the male fertility genes so-called    ampliconic genes and the abnormal sperm characteristics such as, slow or morphologically abnormal sperm. And more specifically, we hypothesize that the variation in the expression levels of these genes, can explain some differences in sperm phenotypes between fertile and infertile men. So hopefully, this study will provide new insights into the reasons behind the male infertility.

Amy Mook:

That's really interesting because, we often hear so much about female infertility and not really male infertility. So when thinking about, “why should the general public care about this research?” What are some of those implications that you have with your research on the field, science, society, those sorts of things that are on a smaller scale?

Marta Tomaszkiewicz:

Yes, yes. Thank you for bringing this up. It's really timely subject. So currently, society treats fertility as a female issue and the woman needs to undergo invasive procedures to evaluate her fertility levels. Yet we know that male factor contributes to around, half of the infertility cases. So I think it's time we investigate the male side of the problem. And in the current study, we are proposing to establish a predictor of male infertility. And additionally, you know having a child is a natural need of most people and we believe that this research will pave the way towards personalized medicine, where a couple can evaluate and in the future may be modulate  their fertility potential, in order to conceive a child. So that that's really the bottom line here.

Amy Mook:

Why is it that we have only studied female and fertility and that there is that lack of information about male infertility?

Marta Tomaszkiewicz: 

  So that is a very important question. And I think that, until now, when it comes to fertility issues, these are only women who are getting evaluated. They are the only ones who are getting a yearly exams with an OB GYN. And we know that the medical infrastructure is mostly male driven, which means that, only the females are getting evaluated and there is a gap that we need to fill. And it's time to address them male infertility now.

Amy Mook:

That's shocking to hear that, male infertility is so prevalent and we don't hear very much about it. Especially as you're saying, that is a common thing for couples to want to have children. And we often think about whether the female is infertile or not. As you're saying, male infertility is not talked about. And I feel like, in my own experience, it feels awkward to even talk about it in general conversations or actual conversations around infertility. 

So how would you suggest and how have you had these conversations, whether that's with your colleagues or just the general public? How do we shape these conversations about male infertility?

Marta Tomaszkiewicz:

Yeah. So, as I said, since last year we are aware that male infertility is becoming an issue because, sperm counts drop worldwide. So I think people start to understand that, it's not only a female issue. So I think, right now it's going to be easier, because we need to start investigate why this sperm counts are happening.

Amy Mook:

So Marta, that's really shocking to hear that the sperm counts are dropping globally. I think that's really so  mething that's intimidating to hear. And so, do you have any ideas as to why that could be happening? What are some of those causal explanations?

Marta Tomaszkiewicz:

So yeah, there are many speculations behind male infertility, but until now, there are no rigorous studies addressing these issues. So one of the reasons could be lifestyle or the diets or different epigenetic factors, but no one has addressed it in a systematic way. So I think it's time we make it our priority.

Amy Mook:

So for those of us that might be interested in how you're going to really investigate this, could you just briefly overview what that research process looks like?

Marta Tomaszkiewicz:

Yeah. So before we embarked on this study, we knew that deletions of the regions containing ampliconic genes, so-called, azoospermia regions, can lead to infertility issues. Such as, spermatogenic arrest or complete loss of sperm cells. But there wasn't really any studies demonstrating the link between the specific genes and specific male infertility phenotypes. So here we propose to study RNA, which it provides real time readouts of these genes in question, and we hope to find the direct associations between the expression levels of these genes and specific sperm phenotype. So the study involves the sample collection, data generation and analysis.

Amy Mook:

You were saying that there isn't really much research around these topics, and we're getting a brief overview of all of the details that go into this research. So I'm assuming that your processes are pretty unique. So could you just highlight some of those aspects of your research that are unique for our audience to learn what's what's new and upcoming?

Marta Tomaszkiewicz:

Sure. As I said before, we knew that deletions of these genes containing ampliconic genes, can lead to some spermatogenic failures. But those studies were focusing uniquely on DNA. And here we are focusing on studies of RNA, which is an active form of DNA and provides these real time readouts. You know, I  t's a barometer of your health. And additionally, we knew that RNA has been a controversial subject for a long time. It was originally dismissed as residual, and I feel that I'm in the right place at the right time, to revisit the subject and apply the most advanced RNA-based technologies to address the male infertility issue.

Amy Mook:

Well, I think I can speak for our audience in saying, we're glad that you feel like you're in the right place at the right time to be doing this.  

[MUSICAL INTERLUDE]

Amy Mook:

I'm assuming that it's not just you being also alone working on this project. So do you have collaborations? 

Marta Tomaszkiewicz:

Yes, absolutely. So most successful projects are usually collaboration, so it is extremely important to identify people with relevant expertise, to accomplish all the aims of the project. And here, genomicists are teaming up with the statistician and the IVF Lab director to perform this research. And it's certainly crucial to support each other in this process and celebrate small achievements during this scientific journey.

Amy Mook:

So what are some of those connections that you have with other campuses?

Marta Tomaszkiewicz:

Galal Abdo. He's the only one from the other campus. He is at Hershey. When I started investigating the human Y chromosome research, we started to be interested in infertility in males. And when we wrote the IRB to collect the samples, we contacted him to collaborate with us and that's how we started. it's surprising that in his practice, no one has any molecular markers for male fertility. All they are focusing on, is whether sperm is multi or morphological normal, but there is no diagnostic tool.

Amy Mook:

Science is certainly a journey. And I know that you're pretty early on in this study itself, but I'm assuming you've experienced some barriers. If you wouldn't mind sharing some of those, what have been those frustrations in science and research, whether it's related to this study or just in general that you've seen during your career?

Marta Tomaszkiewicz:

Yes. So it's definitely  bad experimental design. I feel it takes months to develop the right hypothesis, but sometimes, it takes even longer to design the right experiments to test that hypothesis. And it's definitely not good to rush into performing your research before giving it enough thought.

Amy Mook:

How did you even get interested in science? I think that that's always such an interesting thing to hear from all these different researchers that we all have such different journeys to get into science, and especially in your specific field. So would you mind sharing how you got interested in science to begin with and then how you started to establish your career?

Marta Tomaszkiewicz:

Sure. My dad, he's an orthopedic surgeon and he always wanted me to become a medical doctor. That certainly sparked my interest in medical sciences. But I was always scared of hospital and drawing blood, so that didn't work out. (LAUGHS)  But then starting during my master's studies, I had lots of mentors, both men and women, who inspired me along the way to become a scientist. And they definitely left an imprint on how I think and how I do things as a scientist.

And I think one of my first experiences in science happened during my master's studies, when my supervisor went on sabbatical and I had to perform cytogenetic studies of the Crustacean species from the Baltic Sea. And I had to start the project from scratch. So I was going from one library to another, looking through the books from early 50's, to look up details about the anatomy of the species. And this was the only way to establish the right protocol for isolation studies of chromosomes in that species. And that's experience certainly made me believe that I could be an independent scientist.

Amy Mook:

That's so cool to hear. I feel like when you're faced with a challenge like that, it can be quite intimidating, I would imagine. So, just hearing that you were able to overcome that and led you to your career is interesting. I also think that, a conversation that could be saved for another day is whether, your dad, what his thoughts are now that you're not a medical doctor and hearing what his perspective is. But, I'm thinking about this podcast and how we're located at Penn State. Why is the Penn State community important to your research?

Marta Tomaszkiewicz:

Penn State with our world-class experts, is in a really unique position to address many health challenges, such as, the global pandemic of infertility. And in our study, genomicists are working with the statistician and the IVF Lab Director, so this research is performed across Penn State campuses.

So from my collaboration with the IVF lab director, Dr. Galal Abdo, I have learned that the only way to evaluate male infertility right now, is to visually assess the sperm phenotypes, such as, motility, morphology, concentration, and semen volume. There are no molecular markers for male infertility and it is a problem.

Amy Mook:

And I think that goes back to what we were saying about, how important collaboration is. And thinking about the mission of CHED itself and how we do want to have those collaborations.  And I'm sure that some of our audience may be a bit more scientific and maybe up in their education, but we may also have some younger scientists that are thinking of pursuing careers, but not quite sure. So do you have any advice for any of our younger audience members that may want to become scientists in the future?

Marta Tomaszkiewicz:

Yes, absolutely. I think my advice would be to get out of your comfort zone and take lots of risks in science, because every challenge is an opportunity and most discoveries come from taking risks.  

Amy Mook:

Yeah,  I think that's such a hard thing to do is, being comfortable taking risks. I think that that's just a hard thing to think about, especially the way society shapes us to just stick to what you know, and not take those risks. But it's interesting to hear that and I think that, I'll even take that advice myself. So obviously you're just starting off with this study and obviously COVID is impacting that as well, but what's next for you and your research, whether that's continuing this exact project or what the future looks like for you?

Marta Tomaszkiewicz:

In the future, using a larger sample size representative of diverse population, including minorities, I would like to design a genetic classifier to predict the fertility potential for both men and women from different populations, to be used routinely in every IVF clinic.

Amy Mook:

Marta, is there anything else that you wanted to share? I feel like there's so much more knowledge up there in your head that we're not pulling out. So is there anything else that you think is super interesting for the general audience to know? Just a general audience I think  are so interested in this idea. Is there anything else that you would want to share with the audience?

Marta Tomaszkiewicz:

For me, the most interesting thing to find out is that, for the longest time, RNA in sperm was controversial and people thought that there is nothing there to study. And only last month, they show that using long read sequencing technology, you can actually pull down the long RNA molecules. And it's super exciting. 

And I think that I'm really lucky that I got the funding from CHED, because, I really want to do this study and I really want to integrate different parts, but I think I will take it one by one. I start with RNA and then I hope to move to proteins and then I hope to move to metabolites, but it's good to start with something. And maybe, already, just by using RNA markers, you can already help out couples out there.

Amy Mook:

Where can audience find you and keep up with this work?

Marta Tomaszkiewicz:

I would be happy to engage in conversations. So you can find me on Twitter. My Twitter handle is "amplicomics" and you can also find me on LinkedIn under my full name.

Amy Mook:

Great. Well, thank you so much for joining us on the podcast today and sharing a bit more about your research and your story. I think it's very interesting and I'm looking forward to following it as you develop your projects. So thank you.

Marta Tomaszkiewicz:

Thank you so much. It was great being here.

[MUSICAL INTERLUDE]

Tracking Traits is a production of Penn State’s Center for Human Evolution and Diversity. Our producer, audio engineer and musical theme composer is Cole Hons, and our logo was designed by Michael Tribone of mtribone design. 

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