The Effects of Induced Polycystic Ovary Syndrome in NAG-1 Transgenic Mice

Student: Nicholas Werner (School of Graduate Studies)

Mentor: April Binder

Abstract

Polycystic ovary syndrome (PCOS) is the leading cause of infertility, and the most common endocrine disorder among women of reproductive age, affecting between 8-12% of the population worldwide. PCOS is characterized by cystic ovaries, hormonal irregularities, and metabolic dysfunction. The metabolic dysfunctions associated with PCOS may include obesity, glucose intolerance, and type II diabetes. Because hormonal irregularities are the primary cause of the metabolic symptoms, they are difficult to treat. However, previous studies conducted on the gene NAG-1 have shown it may prevent metabolic disorders when overexpressed. Studies on NAG-1 have focused on diet induced metabolic disorders, and not hormonally induced disorders like those seen in PCOS. Our study focuses on NAG-1, and if it can prevent any of the metabolic disorders associated with PCOS. To study this, we induced PCOS in mice via dihydrotestosterone (DHT) implant, and monitored them for 90 days, after which tissue and serum samples were collected for analysis. We observed no change in weight between the NAG-1 DHT and placebo groups, suggesting NAG-1 may prevent hormonal induced obesity. We also observed no changes in adipocyte sizes between the NAG-1 groups. DHT treated animals entered puberty at an earlier age than placebo groups and ovarian dysfunction was observed. DHT treated animals had disrupted estrus cycles and significantly less corpus lutea in their ovary, suggesting altered ovarian function. WT placebo and DHT groups had significant differences in all aforementioned metabolic phenotypes. Our findings suggest that overexpression of NAG-1 may prevent some metabolic dysfunctions associated with PCOS.

Presentation

14 thoughts on “The Effects of Induced Polycystic Ovary Syndrome in NAG-1 Transgenic Mice”

  1. Nick,
    I don’t see any other comments on here probably because you are so thorough. Great job! I felt you were extremely clear in your explanation and study. Keep up the great work!
    Madi

  2. Nice Job, Nick. That was fun to watch and very well done. I really liked how you put the images of the cells alongside the data figures — that made your talk even more informative. The histology tour at the end was also really nice — I enjoyed it even though you were showing animal cells…. and fat, no less. Your flow was great and you did a good job of making your objectives clear and discussing the methods and results. Even a botanist could understand it. I am looking forward to seeing your thesis defense soon. Take care.

  3. Hello Nick,
    First of all, I want to say that this was a great presentation and your research project was so interesting. In regards to this disorder affecting 8-12% of women and being the leading cause of infertility. You also discussed how this disorder may also lead to Type II diabetes. Do you think it would be a good idea to use CRISPR-Cas 9 to edit the gene affected in mice, thus preventing any endocrine disorders such as diabetes?

  4. Michelle Kakadelis

    Hi Nick-

    This was a very easy presentation to follow and gave a good overview of the topic before diving into the heart of your research. I especially found the discussion of brown fat vs. white fat interesting. Do you have any theories on why the brown fat in the wild type DHT mice was so much higher than their NAG-1 counterparts? In most of the other comparisons between WT/NAG-1, it seemed like the same relative trend held between the treatment groups. However this is clearly not the case here, and I’m wondering what your thoughts are on that.

  5. Nick, this was a fantastic presentation. It was easy to follow along and could be understand by those who many not have a strong biological background. You had a great flow and spoke clearly with confidence. I found it fascinating how the NAG-1 gene has the potential to prevent metabolic syndromes such as PCOS. I hope that you continue with this research so that we can take steps to perhaps implement this in humans!

  6. Hi Nick,
    Very good presentation. It was very clear in what you were testing and really enjoyed all of the figures you added to supplement you data. The estrus cycle graphs were very helpful for seeing how much DHT effected the mice’s cycles. I was wondering even though the NAG-1 mice have less brown fat tissue than the DHT mice, is the brown fat in the NAG-1 more efficient metabolically and what could be the reasons for this?

  7. Wow, that was intense! You did a great job of organizing your presentation and breaking down your research so that it was easily understandable. Your graphs and pictures were great and really added to clarify your points. I found the adipocyte histology section very interesting! Before watching your presentation I didn’t realize that white fat cells grew in size rather than in number. I was also intrigued by the metabolic capacity of brown adipose tissue and its supposed transformation into white adipose tissue. Great job!

  8. Hello Nick,
    Well done. This is a very clear and informative presentation. I was particularly drawn in by your mention of brown adipose tissue. Your explanation for the elevated number of brown adipocytes in the WT/DHT mice was that they are turning into white adipocytes and thereby losing their metabolic function. It’s intriguing and I wonder if and how that information translates to humans.

  9. Great presentation. A member of my family and many of my friends suffer from PCOS. Do you think that there could be any clinical applications of your research?

  10. Interesting research! I loved your visuals, particularly your use of slide visuals to complement your examples. Your graphs that showed that treated mice had incomplete cycles fluctuating between diestrus and proestrus and also that these mice had significantly less corpus lutea were great illustrations of infertility. I am curious if you were able to observe where in the process the estrus cycle was breaking down? Could synthetic hormone replacement be a treatment for PCOS in humans, or is NAG-1 interfering at another stage of the process?

  11. Hello Nick!

    Great presentation! Loved learning about PCOS and how there is this gene that can be manipulated with to help with the disorders caused by PCOS. However, it was seen that there was a large number of brown adipose tissue in the wildtype DHT mice, but I was wondering why you said that this brown adipose tissue could be converting to white adipose tissue and leading to some of the weight gain seen in those with PCOS? How exactly would that happen?

  12. Hailey Krahenbuhl

    Hi Nick, great presentation! I have one question. You mention how the over expression of the NAG-1 gene may be able to prevent obesity due to metabolic dysfunction in those with PCOS. However, what did you find regarding other metabolic dysfunctions such as glucose intolerance and the rate of type 2 diabetes in those with PCOS? Again, great job!

  13. Hi Nick,
    It is very interesting to learn more about Polycystic ovary syndrome (PCOS), and how we experiment on mice. Your research gives an idea of what to do and what to expect for the experiment. Would you mind telling me how you discover NAG-1? I am curious about the methods and techniques you used in the experiment! Great job Nick!

Leave a Reply

Your email address will not be published. Required fields are marked *