Meet Richard McCosh – A Researcher that Tackles the “Brainy” Side of Reproduction

Posted by Ariane Pessentheiner on October 15, 2020 in Hormones, Science communication, Stress | Leave a comment

Have you heard of Lonesome George? The tortoise? He was long known as the rarest creature in the world, because he was the last existing individual of the Pinta Island tortoise species in the Galapagos Islands before he died in 2012 [1]. The existence of every species on earth is dependent on successful reproduction. If this is impossible because of missing partners or reproductive issues, a species is likely to become extinct, making reproduction one of the most important aspects of life.

In my second interview, I talked to Richard McCosh, a postdoctoral scientist in the department of Reproductive Medicine at UC San Diego in the laboratory of reproduction specialist Dr. Kellie Breen. He was born and raised in San Diego, but his research career started at Montana State University, continued in West Virginia and now brought him back to San Diego. Initially, he wanted to become a veterinarian, but his first contact with research labs changed his mind. “A couple of months in, I realized that I really liked laboratories and I realized that (they are) doing all of the fun stuff and none of the hard stuff – that kind of started it for me.”

At the time he was working on the reproduction of sheep and cattle in an agriculture department at Montana State University. Knowing what influences the monthly cycle in female cattle and sheep is an important aspect of agricultural production. If the menstrual cycle of the animals is synchronized, they can be fertilized at the same time which reduces labor costs and increases cattle crop. In this agriculture department the main focus was to apply knowledge from research to help farmers increase their production, but Rick wanted to dig deeper and was intrigued to find out how fertility is controlled. “After a lot of reading, I kind of decided to study control of gonadotropin secretion, the hormones that tell your ovaries and testes what to do,” he explains and adds: “They are organized by a bunch of neurons in the hypothalamus and that just stuck out to me – that is what I wanna work on, how these neurons turn off and on.” This led him to move to West Virginia to study exactly that during his doctoral research – how the brain controls gonadotropin release.

Can you remember when you went through puberty? All these times when you felt awkward and cranky? Well that’s understandable, because during puberty, your body and brain are going through a lot of changes. Gonadotropins have quite an important role in these processes. They are a group of hormones released by the brain (more specifically by the pituitary gland in the hypothalamus – you can see its location in the cartoon) and also by the placenta during pregnancy. Two very important members of this family are called follicle stimulating hormone (FSH) and luteinizing hormone (LH). Gonadotropins are needed for a normal sexual development during puberty in both men and women because they signal our reproductive organs to work properly which means that testes produce sperm and ovaries produce and release eggs. So, you can imagine that losing those signals causes a bunch of problems. Sexual development does not occur properly because gonadotropins also stimulate the release of other sex hormones and when not treated with hormone replacement therapies, affected people suffer from infertility [2,3]. Even after puberty, these hormones dictate normal fertility. Gonadotropin release has to be exactly timed through the action of specific neurons during the menstrual cycle. If this clockwork is out of sync, also fertility is affected.  This is what Rick tries to tackle in his research [4].

Fertility and everything that comes with it is an extremely complex topic. With increasing cases of infertility worldwide (at least 50 million couples worldwide are not able to conceive naturally), it is also an eminent research topic [5]. Many aspects of fertility are still poorly understood. Among couples who are affected by infertility, some get the diagnosis “idiopathic infertility”, meaning that the reasons for their condition cannot be identified by the current diagnostic methods. I am one of these people, therefore I am grateful that researchers like Rick take it upon themselves to better understand the processes that occur during reproduction, which in the future could revolutionize current diagnostic standards or treatments.

In his lab in West Virginia, Rick worked primarily with sheep, but many of the aspects that he was studying could be applied to humans. “Their estrous cycle is very similar to the human estrous cycle, much more similar than rodents.” Also, they are quite docile animals. When I asked what daily work with sheep looks like, Rick smirked and said: “When humans come then they bring food and treats () and you just grab them and after a few times they (the sheep) get used to it. Some of them could be a little wild at first, but then they are fine.” That allows the researchers to take blood samples which they can analyze afterwards.

Rick moved back to San Diego after his doctorate when he found a position in a laboratory under the mentorship of Dr. Kellie Breen that studies how stress influences the neuronal networks and sex hormones during reproduction. “It’s pretty established that various types of stress can inhibit fertility and disrupt menstrual cycles,” Rick explains.

But what happens in our bodies when we are stressed? Stress is a natural physical and mental reaction to life experiences. Imagine a stressful situation like being late to an important meeting – your heart beats faster, your breath quickens, and your muscles get tense and ready for action. These reactions are controlled by our hypothalamus (the same part of the brain where also sex hormones are coming from), which releases stress hormones. Thus, your body is put in a fight-or-flight state, no matter which stressful stimuli occur. Stress can also come from within the body, for example metabolic stress, which is the stress caused by a sudden drop of blood sugar levels as seen in some diabetic patients. If stressful periods occur persistently, it has severe negative effects on our health. Among those is the deactivation of reproductive processes, which are also initiated in the hypothalamus. This makes sense because reproduction requires a lot of energy which the body redirects to deal with the stress it’s under.

Speaking from personal experience, I know how stressful trying to have a baby can be. One of the statements that most infertile couples hate is: “Once you are relaxed, it will happen.” But what is the scientific evidence for an effect of stress on reproduction in humans? “That question is really hard, because there is no good data that tracks that in healthy women. () Unfortunately, results in humans are a bit anecdotal,” explains Rick. “This is an issue that is understudied, especially in young women.” Indeed, studies dealing with this topic in humans are controversial [5]. The problem with these human studies is that there are a lot of factors that researchers cannot control, like honesty when filling out questionnaires or adherence to study protocols. Therefore, Rick is studying the effects of stress on the reproduction of mice. Even that comes with difficulties. “They are so sensitive to stress that we handled their tails (in order to take blood) for five weeks before we start experiments. After a couple of weeks, they get much easier to grab. They learn.” Rick even wrote guidelines for other researchers to explain how these techniques are best done to get reliable results [6]. In the end, the animals should only react to the stress that the researcher deliberately applies.

With his studies, Rick has shown that the acute stress of low blood sugar shuts down a certain set of neurons which in turn leads to a reduced release of the hormone LH [7]. So, yes, intense stress might influence the female cycle, especially if it happens during certain times when the release of LH and FSH needs to be strictly timed [8]. Rick’s studies give us new insights in the processes that occur in the brain which could be similarly true in humans. Future studies may give us clearer insights into how much stress really influences our fertility.

In the future, Rick wants to have his own lab to further pursue his passion for basic research. “I just love neurons and looking at how they are connected. So, on a day to day basis, this basic science part is what gets me,” he concludes. I agree, this passion is shining through in every aspect of our interview. While we were having our interview, he was taking another step in reaching this goal by applying for funding for his research. And when not in the lab or the office, you might meet him at the tide pools in La Jolla, which are his favorite place in San Diego. Let’s wish him luck for his scientific journey, wherever it might lead him next!

References:

[1] https://en.wikipedia.org/wiki/Lonesome_George

[2] https://www.chuv.ch/en/hhn/hhn-home/patients/learn-about-gnrh-deficiency-kallmann-syndrome

[3] Coss D.Regulation of reproduction via tight control of gonadotropin hormone levels.  Mol Cell Endocrinol. 2018 Mar 5;463:116-130. doi: 10.1016/j.mce.2017.03.022. Epub 2017 Mar 22. PMID: 28342855

[4] McCosh RB, Szeligo BM, Bedenbaugh MN, Lopez JA, Hardy SL, Hileman SM, Lehman MN, Goodman RL. Evidence That Endogenous Somatostatin Inhibits Episodic, but Not Surge, Secretion of LH in Female Sheep.  Endocrinology. 2017 Jun 1;158(6):1827-1837. doi: 10.1210/en.2017-00075.

[5] Palomba S, Daolio J, Romeo S, Battaglia FA, Marci R, La Sala GB. Lifestyle and fertility: the influence of stress and quality of life on female fertility. Reprod Biol Endocrinol. 2018 Dec 2;16(1):113. doi: 10.1186/s12958-018-0434-y. PMID: 30501641

[6] McCosh RB, Kreisman MJ, Breen KM. Frequent Tail-tip Blood Sampling in Mice for the Assessment of Pulsatile Luteinizing Hormone Secretion. J Vis Exp. 2018 Jul 4;(137):57894. doi: 10.3791/57894.

[7] McCosh RB, Breen KM, Kauffman AS. Neural and endocrine mechanisms underlying stress-induced suppression of pulsatile LH secretion. Mol Cell Endocrinol. 2019 Dec 1;498:110579. doi: 10.1016/j.mce.2019.110579. Epub 2019 Sep 12. PMID: 31521706

[8] McCosh RB, Kreisman MJ, Tian K, Ho BS, Thackray VG, Breen KM. Insulin-induced hypoglycaemia suppresses pulsatile luteinising hormone secretion and arcuate Kiss1 cell activation in female mice. J Neuroendocrinol. 2019 Dec;31(12):e12813. doi: 10.1111/jne.12813. Epub 2019 Dec 12. PMID: 31758872