Our conversation further delves into the potential of this pioneering research to help diagnose ovarian remnant syndrome in cats. Alan and Aime will impart their enlightening findings on the cyclicity of these hormones and their connection to a cat's follicular activity. Learn about their manuscript's journey from submission to publication in JAVMA. You won't want to miss this captivating discussion as we spotlight the impressive impact their work has had on the veterinary medical field. Hosted by Associate Editor Dr. Sarah Wright and Editor-in-Chief Dr. Lisa Fortier.
INTERESTED IN SUBMITTING YOUR MANUSCRIPT TO JAVMA ® OR AJVR ® ?
Our conversation further delves into the potential of this pioneering research to help diagnose ovarian remnant syndrome in cats. Alan and Aime will impart their enlightening findings on the cyclicity of these hormones and their connection to a cat's follicular activity. Learn about their manuscript's journey from submission to publication in JAVMA. You won't want to miss this captivating discussion as we spotlight the impressive impact their work has had on the veterinary medical field. Hosted by Associate Editor Dr. Sarah Wright and Editor-in-Chief Dr. Lisa Fortier.
INTERESTED IN SUBMITTING YOUR MANUSCRIPT TO JAVMA ® OR AJVR ® ?
You're listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode we chat about anti-Mullerian hormone and inhibin- B concentrations and non-ovulating queens and how they may help determine the gonadal status in cats.
Dr. Lisa Fortier:
Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today, we have Alan and Aime joining us. Alan and Aime, thank you so much for taking time out of your busy schedule to be with us here today.
Yeah, so anti-Mullerian hormone and inhibin- B are glycoprotein hormones. They're both synthesized and secreted by the granulosa cells inside of the ovarian follicles. AMH is a hormone that a lot of veterinary students will know from sexual differentiation. It's the hormone that's involved in assuring that the male develops the male essentially internal genital structures. But people don't realize that while that makes it a male hormone, it's also secreted in females, though at much lower levels, and because the granulosa cells secrete them, they're good markers for the presence of granulosa cells and therefore the presence of ovarian follicles and ovarian tissue.
Dr. Sarah Wright:
That takes me back to physiology days and such. Alan, what were some of the important findings from this study?
Dr. Alan Conley:
We were really pleased that these aren't easy studies to do and Aime needs to take credit for what I think are some of the more interesting data that we got from the study, which was to say that anti-Mullerian hormone and inhibin- B seem to their concentrations in the circulation seem to fluctuate in concert with cyclicity in those queens if they did not ovulate in other species.
Dr. Alan Conley:
Anti-Mullerian hormone is thought to be very stable during the cycle and not vary as it does in the queen. So we're a little surprised to see how variable it was and pleased that it seemed to correlate with a physiological function. So yeah, it was kind of exciting and then, as long as those are there and measurable, then they are very good markers for the presence of ovarian tissue and gonadal status. I guess I should mention the other really important part of the study and this we were lucky to be able to collaborate with Fiona Hollinshead at Colorado State that helped to supplement our samples, that enabled us to look at populations of queens, a true population-based reference range that we established and I think that for any hormone and actually for any biochemical parameter, it's really important to determine a reference range in order to interpret results from cases that might be submitted, and I'm pleased to say these are the first reference ranges that have ever been determined and reported in cats.
Dr. Lisa Fortier:
Alan was part of that developed with Ned Place, my colleague at Cornell. Do I remember that?
Dr. Alan Conley:
Yeah, so Ned Place, a good friend and long-term colleague, Ned, actually kicked this whole thing off. So back in a decade, 12 years ago, we were working on AMH in horses and Ned was working on AMH in dogs and cats and he was the one who first published a very seminal paper showing that AMH was measurable in bitches and in queens and therefore was a useful marker for gonadal status and, more importantly, ovarian remnant syndrome, which can be problematic by way of diagnosis. Yeah, and so Ned really kicked this whole thing off. Yeah.
Dr. Lisa Fortier:
That's great. He was, well still is, head of IACUC when I was at Cornell. He's a really fabulous leader, so I'm glad to hear of him and other sides of the research equation as well.
Dr. Alan Conley:
Yeah.
Dr. Lisa Fortier:
Thanks Ned.
Dr. Alan Conley:
And unusual because you know, Ned is an MD, right and PhD and he does a remarkable job fitting in veterinary medicine and his work in the endocrine lab at Cornell is spectacular, yeah.
Dr. Lisa Fortier:
Yes and connected us. So thank you. Aime, I turn to you for a moment. What sparked your research interest in reproductive hormones? I know you come from an equine background and when I told you earlier, like when I first saw this title of this manuscript, I was like whoop dee doo, we've known that in horses forever but, as Alan just said, there's some differences that surprised you guys in cats. But in general, what sparked your research interest in reproduction?
Dr. Aime Johnson:
I've been involved in cat research almost since I got to Auburn. My story just a little bit. There is a pretty robust research colony here of cats that look at human clinical diseases. They're a model for human clinical diseases and they were having trouble with their reproduction and asked the theriogenologist to step in, and so I answered that call and ever since then I've been very heavily involved in this colony with the reproduction status to get them affected kittens and other kittens for their research.
Dr. Aime Johnson:
But cats are cats are a different beast, even more so more different than horses. They're a different beast. They're very interesting hormonally and there's just not a lot of data out there for cats in general, especially for reference ranges, and certainly not longitudinal data where we're following the same group of cats over time, where we've got one group of cats over several months that we were able to do blood draws on, and so that's pretty rare. As Alan said, reference ranges in cats and certainly some of the other species, but certainly in cats are almost non-existent, and so being able to determine reference ranges was a big, big deal for this project. And clinically I'm a clinical theriogenologist as well and so we get calls all the time about possible ovarian remnant syndrome and so better to diagnose. That is kind of what helps spark the interest in doing this to see if we could help the practitioners out there better understand these reproductive hormones and how they work.
Dr. Lisa Fortier:
Yeah, we certainly appreciate that and, as the editor, I marvel every day how few feline manuscripts are out there, like they're obviously very popular cats, but just very few. So when we saw this one coming through, I was like, oh yay, obviously really great work and clinically super impactful. So just want to give you guys a thank you for sharing it with JAVMA and all of our readers. So thank you and for being here again today. Amy, what inspired you to write this manuscript? It's one thing to have the idea and you gave credit you guys are obviously great colleagues with other people and giving credit around the table but what really inspired you to gather up this data, think through it and write this manuscript?
Dr. Aime Johnson:
I think once we saw the data we knew we had to write the manuscript Again, just being able to do the reference ranges that, not having that published anywhere, we really needed to get that information out to the practitioners. Then, once we saw that the AMH and the inhibin-B are cyclic and the cat that's not that way in other species, we had to get that out there to as many people as we could to let them see the reference ranges.
Dr. Aime Johnson:
Ovarian remnant syndrome can be very difficult to diagnose in different cases. Again, I take a couple calls. Certainly, maybe a call a month about ovarian remnant syndrome in other species, but a lot of times it's in the cat. Getting this manuscript out there to help diagnose, it was mandatory for us.
Dr. Lisa Fortier:
That's great. Not only mandatory, but it sounds passionate. This is really important. You both have alluded a little bit to well. That was different and surprising. We weren't expecting that, and maybe not what's the most important, but again, maybe tell our listeners what was the most surprising finding from the manuscript.
Dr. Aime Johnson:
We've already alluded to it to find that these hormones mirror the follicular growth and the cyclicity of it, that AMH and inhibin- B go up when the follicular activity goes up and they come down when the follicular activity goes down. We know cats are induced ovulators so they don't ovulate unless they are bred for the most part. Now some of the cats in our study did spontaneously ovulate. That we were able to diagnose. That helped as well, because we saw that cyclicity actually eliminated when those cats were in diestrus. That was the most surprising thing for me was to see it mirror their cyclicity and to be able to follow these cats over time, where over a three-month period where we were able to take blood on them twice a week and also do vaginal cytologies and be able to mirror that and correlate that with their hormone profile.
Dr. Alan Conley:
If I can. The clinical relevance of this is that if you have a cat you suspect is not spayed or has a remnant, I'm often asked when's the best time to take a sample. Our study suggests that the best time to take a sample is at the time that cat is in apparent estrus. That's when AMH and inhibin-B concentrations are going to be their highest. That's the best time to sample. The other thing that we've not touched on but was surprising to me in the study was in cats that we were confident were actually spayed, based on undetectable AMH and inhibin-B concentrations, their progesterone was certainly at a level. Some of those cats maybe six out of 60, had progesterone concentrations that I would have interpreted as being luteal and therefore indicative of an ovarian remnant and ovulation. In fact, I think we can only surmise that that progesterone in a stressed animal enough can come from the adrenal gland to look like the cat has luteal tissue. I was very surprised at it. I think Aime was too.
Dr. Sarah Wright:
That's fascinating. I think this is really going to be a game changer for feline practitioners. Thank you so much for sharing this with JAVMA.
Dr. Alan Conley:
I think that it's the decision to do an exploratory laparotomy has big consequences. You want to be as sure as possible that you're going to find something, because those remnants can be very small and you don't know when to stop looking.
Dr. Sarah Wright:
You remember learning about that in vet school and I'm like that sounds terrifying. Hopefully this helps some early career feline practitioners as well. And Alan and Aime, you're both very accomplished and we just again really appreciate you sharing this work with us. Aime, how did your advanced training prepare you to write this manuscript?
Dr. Aime Johnson:
Again, I'm a clinical theriogenologist, so I'm not necessarily a researcher by trade, but I've done a lot of research and been involved with a lot of research, but certainly from a clinical aspect we saw a problem and wanted to see if we could fix it, and so that's where a lot of the research, the clinically relevant research, comes from, where you've got practitioners such as myself that see this need out in the practitioner world, get questions and things like that that we want to answer.
Dr. Sarah Wright:
You definitely addressed the knowledge gaps. How did your advanced training prepare you to write this manuscript?
Dr. Alan Conley:
I had several years in practice and so that gives me appreciation for the real world. That helps. That helps a lot actually. I've been involved in comparative reproduction for close to 40 years now, worked on a bunch of different species, including human primates, with Ned Place. I got to know Ned working on spotted hyenas at Berkeley, a carnivore so all of this gives me a very broad comparative perspective so that when we look at different species I expect them to be different. I'm surprised more often surprised when they're not and, as Amy pointed out, cats are a very different beast. So it helped prepare me for whatever we might have found, and running the clinical endocrinology lab for almost 15 years now it's been a bit of a mission of mine actually to establish reference ranges for as many reproductive hormones for as many species as we possibly can, because I think it really improves our diagnostic value. Yeah, that's great.
Dr. Sarah Wright:
It's very important work, so thank you. Now this next question is very important for our listeners, Alan. What is one piece of information the veterinarian should know before discussing this topic with the client?
Dr. Alan Conley:
I think the single most important thing for practitioners, and especially for owners to understand is that no test is perfect, but our analyses do have very real value for helping in the diagnosis of ovarian remnant syndrome and that very important decision of whether or not an exploratory laparotomy is warranted.
Dr. Sarah Wright:
And then to flip things around, what is one piece of information the client should know before thinking about this for their cat?
Dr. Aime Johnson:
I think certainly the decision to go to surgery is not one made lightly by the veterinarians and certainly not taken lightly by the owners, but I think it's important for them to also know that no test is perfect and that running multiple tests help us get the bigger picture. The other thing to remember is that the amount of AMH present is dependent on the size of the ovarian remnant that's left, and so some of those tests may be inconclusive if it's a very small piece, and so it gets frustrating to owners, and sometimes multiple tests, and multiple doing them over a period of time, helps us get a clinical picture.
Dr. Lisa Fortier:
Yeah, fantastic. Thank you again. As we wind down, we try to ask a couple more personal questions so the readers and listeners and us can get a little insight into you too. So, Alan, we'll start with you. Clearly very accomplished. As Sarah said earlier, we have some shared history in living in North Dakota, so you have resilience. We know that. Where do you think your resilience, determination, inspiration came from?
Dr. Alan Conley:
Honestly, the work is just intellectually interesting and for me if it has practical value then that's just added incentive and as long as I believe that I'll be in the business.
Dr. Lisa Fortier:
Fantastic. I feel the same way. I'm so blessed to be Editor- in-C hief and learning all of this new stuff every day. It's really every day's a school day. Aime, for you, Sarah, and I love the answers to these questions. What is the oldest or the most interesting item, either in your desk or on your desk?
Dr. Aime Johnson:
As a theriogenologist. I have a lot of sperm memorabilia. So I've got a stick drive here that the head of the sperm is the actual stick drive and the tail is the cap. That's usually in my drawer. And then I also have a little sperm squishy ball that you can get a little stress, stress, squishy ball sperm. That's on the desk as well.
Dr. Lisa Fortier:
And then you can like, twirl it around by the tail or smack it around. Your computer needs to be rebooted.
Dr. Alan Conley:
You need the earrings to go with that.
Dr. Aime Johnson:
I do have earrings, I just didn't wear them today. There you go. And then we have a zebra sperm as well.
Dr. Sarah Wright:
That's awesome. Well, just thank you both again. We appreciate your time and also appreciate your contribution to JAVMA.
Dr. Alan Conley:
And thank you very much, as we say that the journal was really really excellent process and we're so pleased to contribute. Thank you.
Dr. Aime Johnson:
It's an honor for us to have written the manuscript and have it included in JAVMA.
Dr. Sarah Wright:
And to our listeners. You can read Alan and Aime's manuscript in print JAVMA or on our journals website. I'm Sarah Wright with Lisa Fortier. Thank each of you for joining us on this episode of the Veterinary Vertex podcast. We love sharing cutting edge veterinary research with you and we want to hear from you. Be sure to leave us a reading and review on Apple podcasts or any other platform you listen to.
