Monday, September 17th 2012

Skaters from the Twin City Derby Girls (including Mrs. Myrmecos) have got the opposing jammer's number. Photo by Alex Wild.
For me, roller derby began with a very steep learning curve. I didn’t know how to skate, I didn’t know the rules, and so every practice left me physically and mentally exhausted. I did bring my own skill set to the sport: I’ve been an athlete my whole life, and played many a contact sport, and so some parts of roller derby – the physical fitness, hitting, body awareness, cross-training and nutrition – came easily.
After a while though, I hit the limit of the edge my athletic performance gave me. And so I had to start reading derby blogs for strategy, increase my off-skates workouts, and learn about roller derby gear to make sure I was using the right materials. I attended some clinics. I tried new moves until spectacular falls became small falls, and small falls became no falls.
I’ve become, I think, a pretty good player. I skate for a young but nationally ranked team, and I have exceptional, talented teammates and coaches (just see a few of them above).
Yet you know enough about sports to know even great teams don’t win every single bout they play, and that when they lose it isn’t always to the more talented team. Most of us understand that in sports, we can’t actually control whether we win or lose. We can only control our preparation leading up to, and our reaction to game conditions.
The best athletes recalibrate their understanding of success: success is less about winning or losing, and more about whether they played their best game. How did they prepare for the event? How did they handle adversity, including bad luck or unfairness? Were they proactive or reactive in the face of their opponents? Did they put in maximum effort?
Success in sport, then, is context-dependent. And to increase your chances of success in the traditional sense (winning), you need to increase your success in the factors that are under your control. You need to get to the point where you can anticipate and handle most contexts.
Academia (heck, most of the jobs of most of you reading today) is the same way. We can control only ourselves and how we react to given situations.
So why are we so hard on ourselves when we fail?
* * *
This summer, my league brought in sports psychologist Dr. Brent Walker to talk to us about how to take the next step in our mental performance. Dr. Walker came as a kindness to a student of his, but was so constructive we would have paid for a million more sessions. Alas, Columbia has just scooped him up from Eastern Illinois University and so now they get to benefit from his wisdom instead.
The first step of our session was to list the factors we cannot control related to performance in roller derby bouts. These included:
- The floor surface (grippy or slick floors impact our ability to do certain kinds of moves)
- Referees
- Fans
- Attitude of the opposing team
- Ability of the opposing team
- Injuries and who we can roster
- Personal, family, or work stressors
- Luck
Then we discussed the importance of planning ahead of time for as many of these factors as possible to better control our reactions. So for instance, if we’re skating in an away bout and don’t know anything about the floor, we bring several kinds of wheels to try out during our warmups.
What are those factors for academics, particularly academic scientists? Here are a few that come to mind for me:
- Whether laboratory materials are delayed, backordered
- Research participant retention issues
- My tenure & promotion committee and their decisions
- My collaborators’ priorities
- My departmental colleagues’ priorities
- My students’ priorities, commitments, responsiveness to my mentoring
- Journals’ manuscript decisions
- Grant reviewers’ decisions
- The quality of the pool I am up against for manuscripts and grants
- My husband’s work priorities
- My daughter’s health and wellness (to some extent – what I mean here is I cannot control when she gets sick and I have to miss work)
- My daughter’s school’s days off
- Crappy luck (things breaking or not working)
What other factors seem to be beyond our control? How do you plan ahead to neutralize or change them?
I’ll have a follow-up post Wednesday on the second part of this exercise. Discuss!
Wednesday, September 5th 2012

Mate with me, and I'll help you ovulate! Oh, yeah. "White Llama" by Petr Kratochvil.
A paper that came out on August 20th in PNAS suggests a factor in semen that could induce ovulation. The idea that this could happen isn’t new, but identification of the factor that might do it certainly is. Ratto et al (2012) contend that they have found The Magical Semen Ingredient That Makes the Ladies Swoon (Then Ovulate), and it is Nerve Growth Factor, or NGF. (Full disclosure: I didn’t notice until I was halfway through writing this post that a collaborator of mine, Roger Pierson, is a co-author on this paper.)
Much of the online conversation I’ve seen about this paper begins with an implication that the research was on or related to humans, then a quick switcheroo to reveal they were, in fact, talking about llamas.
Yes, llamas.
Which are an admittedly cool species, one which my generation of Sesame Street watchers no doubt remembers from this song:
[youtube http://www.youtube.com/watch?v=sgkYHhG18uc&w=420&h=315]
And that same generation now reads to their own children Llama Llama Red Pajama, Llama Llama Mad at Mama, and the rest of the Llama Llama series by Anna Dewdney (we have nearly all, and my daughter can recite most from memory). It’s fun to say, it rhymes with a lot of stuff, and they can spit at you. What’s not to love?
But, well, llamas aren’t humans. So I’m going to explain why this distinction is important, why this research is still really cool, and the reasons I can see that make NGF interesting in humans after all.
Bet you can’t make me ovulate!
Some animals ovulate with the act of intercourse – either the physical act stimulates it, or there is some factor in the semen that signals that it’s time to pop out that egg. Such an animal is called an induced ovulator, and this group includes llamas, the rest of the camelids (camels, alpacas), but also cats, minks, voles, and a few others.
The other kind of ovulator is the spontaneous ovulator. This is far more common and this is how we primates ovulate. Spontaneous ovulation is when ovulation is triggered spontaneously and internally via the suite of hormones that nourish and mature egg follicles. This is why you often see a distinction in the infertility literature between “spontaneous” cycles that occur naturally, and “stimulated” cycles that are brought about using fertility drugs (which are just synthetic versions of the hormones we produce).
So there is room for an external mechanism to influence ovulation, even in spontaneous ovulators. We have scores of papers showing that energetic stressors (particularly not eating enough) can delay or cease ovulation. Issues with insulin, thyroid hormone or androgens (take your pick, it’s a murky mechanism) can make too many follicles ripen at once then struggle to ovulate, leading to a diagnosis of polycystic ovarian syndrome (PCOS).
But that’s not quite the same thing as The Magical Semen Ingredient That Makes the Ladies Swoon (Then Ovulate).
Oh, the things NGF could do that are good for you
In llamas, the discovery of NGF and its abilities supports the hypothesis many have held that there is something in semen whose specific purpose is to stimulate ovulation… among induced ovulators. And the discovery that it’s NGF, and not some newer, whacked-out chemokine that had never before been identified, suggests we are looking at a fairly conserved (evolutionarily old and passed on among many modern species) feature.
This alone is striking and important.
What else does NGF do, and why would this be the trigger for ovulation in llamas and their fellow induced ovulators? NGF has a lot of other jobs, mostly related to in utero development of the central and peripheral nervous system, and neuroendocrine or immune tasks once born (Levi-Montalcini, 1987).
But NGF has also already been examined for a possible role in ovarian function. And its role is quite interesting!
NGF appears to facilitate ovulation. In the hour leading up to egg release, trkA (tyrosine kinase receptor) and NGF gene expression increase in the ovary (Mayerhofer et al., 1996). What seems to happen is that NGF activates trkA receptors in a way that eventually leads to a degradation of the follicular wall, which aids in follicular rupture from the ovary. Breaking down the ovary’s last arguments about why the egg shouldn’t get to go out that night, NGF is like a feisty aunt that encourages troublemaking.
If this aunt spoils the egg too much, or doesn’t see enough of her, problems can arise. In one sample of women seeking assisted reproductive technology, NGF was found to be higher among women with diminished ovarian reserve, but lower among those with PCOS (Buyuk and Seifer, 2008). Yet a different study found NGF associated with PCOS in a mouse model, and high NGF in women with PCOS (Dissen et al., 2009). Both studies measured NGF in follicular fluid in women during assisted cycles to try to get pregnant: the Buyuk and Seifer (2008) collected during egg retrieval, but the Dissen et al (2009) doesn’t say when (it would make sense to assume the same time-point, though).

Follicular fluid NGF is higher in women with low ovarian reserve, and lower in women with PCOS, in this sample (Buyuk and Seifer 2008).

Different results despite a similar sample population and sampling methods? It might mean we don’t understand the mechanism that well yet. It could also point to the fact that PCOS is a hugely variable syndrome, likely with multiple origins, and so you could potentially get different samples with different NGF concentrations by chance and still have both studies be meaningful. Either way, NGF seems like a very important factor to consider in PCOS, since in some PCOS women we are seeing maturation of many follicles but no ovulation.
So how else might NGF be stimulating ovulation?
Maybe NGF stimulates luteinizing hormone!
This is the pathway the authors of this paper propose (Ratto et al 2012). Rather than NGF acting in some paracrine (cell to cell) manner, they contend NGF zooms over to the anterior pituitary (in your brain), which makes luteinizing hormone (LH), and the LH then zips to the ovary and tells it to put the finishing touches on the egg and let it go.
If we’re talking about locally produced (by the woman) NGF, this all makes sense to me because it would be part of her own spontaneous cycle regulation. Here’s what I don’t get. If semen-derived NGF were to induce ovulation it probably wouldn’t happen in time for that ejaculate’s sperm to have a follicle to fertilize. So this would really only work if someone was having sex regularly so that an earlier episode could prime a later fertilization. In a promiscuous species, which is somewhere in our ancestry, this seems like a terrible idea. You might be wasting your mating effort ripening a female’s eggs so that some other schmo gets to fertilize them! This is why to me, semen-derived NGF is currently in the “may not help, but doesn’t hurt” category for now when it comes to spontaneous ovulators like us.
Maybe NGF stimulates mast cells!
Or perhaps the mechanism is an inflammatory one? NGF activates mast cells, which degranulate (release histamine) and start the inflammatory process. Mast cells in the endometrium produce tryptase which induces angiogenesis and neovascularization (making new blood vessels). But endometrial mast cells are the most activated just before menstruation (Salamonsen and Lathbury, 2000). In fact, tryptase activates matrix metalloproteinases (MMPs), which break stuff down, which is why they are so important to menstruation. However, some think histamine could be a paracrine signal involved in decidualization and implantation (Noskova et al., 2006). So… NGF could facilitate menstruation if timed towards the end of the cycle, or implantation, if timed during the implantation window.
Llama Llama Ovarian Drama
Intra-ovarian NGF is an important component of the mechanism of ovulation in spontaneous ovulators, and seminal NGF is important for ovulation in induced ovulators. It’s entirely possible the seminal NGF is also important to women’s reproductive function in some way. My big questions – and I really hope someone does follow-up work on this – are what is a physiologically relevant concentration of NGF in spontaneous ovulators (so, how much you need to actually do anything), and what produces variation in intra-ovarian NGF? I’m very curious whether gonadotropins, hormones, or external factors influence any of this stuff. Considering intra- and extra-ovarian sources of variation in ovulation just made lady parts that much more interesting!
References
Buyuk E, Seifer DB. 2008. Follicular-fluid neurotrophin levels in women undergoing assisted reproductive technology for different etiologies of infertility. Fertility and Sterility 90(5):1611-1615.
Dissen GA, Garcia-Rudaz C, Paredes A, Mayer C, Mayerhofer A, Ojeda SR. 2009. Excessive ovarian production of nerve growth factor facilitates development of cystic ovarian morphology in mice and is a feature of polycystic ovarian syndrome in humans. Endocrinology 150(6):2906-2914.
Levi-Montalcini R. 1987. The nerve growth factor 35 years later. Science 237(4819):1154-1162.
Mayerhofer A, Dissen G, Parrott J, Hill D, Mayerhofer D, Garfield R, Costa M, Skinner M, Ojeda S. 1996. Involvement of nerve growth factor in the ovulatory cascade: trkA receptor activation inhibits gap junctional communication between thecal cells. Endocrinology 137(12):5662-5670.
Noskova V, Bottalico B, Olsson H, Ehinger A, Pilka R, Casslén B, Hansson SR. 2006. Histamine uptake by human endometrial cells expressing the organic cation transporter EMT and the vesicular monoamine transporter-2. Molecular human reproduction 12(8):483-489.
Salamonsen LA, Lathbury LJ. 2000. Endometrial leukocytes and menstruation. Human Reproduction Update 6(1):16-27.