I’ve been interested lately in mouse embryo transfer surgeries. It’s the murine cousin to human in vitro fertilization (with the drastic difference that the egg donor is euthanized in the process). It’s one step in the process of making transgenic mice. You start with a pregnant mouse. You kill her to “harvest” fertilized mouse eggs. You insert genes you’ve synthesized in the lab into the fertilized egg in a Petri dish, and then you surgically implant these genetically-modified eggs into a surrogate mother mouse.
Embryo transfer is a very common surgery in laboratories, but no one has ever published a really good assessment of just how painful it is to the surrogate mother mice. I’d anticipate it to be moderately painful as surgeries go – not trivial, but not excruciating; worse than having a tooth pulled, but not so bad as having a bone set. There’s some work being done on whether various painkillers will affect the success of the procedure for better or worse, including a project I’ve been working on. So I took a quick look at a new report tangentially related, i.e., how in-lab handling of embryos might affect success of mouse embryo transfer.
Talk about hiding your animals off-stage! My job in this blog is to bring readers backstage to meet the animals behind the science. In this report out of the University of Michigan, those animals are all but invisible. You mightn’t even realize they existed, without me here to guide you. The authors report that zygotes (i.e., the fertilized mice eggs) were isolated from mouse oviducts. You could almost think that oviducts are free-living entities, but they’re not; they are organs in the mouse abdomen, and you can either remove them by surgery, or you can kill/euthanize the mouse and remove her zygotes. These mice were surely killed for their embryos (though that’s not at all explicit in this report), and how they were killed raises humane questions. It also raises scientific questions, as method of euthanasia and time from euthanasia to retrieving the mouse embryos might affect their viability in a Petri dish and later, in their surrogate mother, which is, after all, the scientific focus of this study.
Not to give this information is bad science, and questionable animal welfare. Live animals are complex; their pain, inflammation, drugs they’ve received and method of euthanasia can affect the biological behavior of the system under study and thus must be reported so the reader can fully understand and assess the validity of the experiment under consideration.
My bigger concern is the statement that embryos were “transferred to oviducts” of mice, without saying how. This requires abdominal surgery (the surgery whose pain hasn’t been well-studied; see above). Surgery requires anesthesia, and in today’s standards for laboratory animal care, it requires post-surgical painkillers as well. You have to at least consider the possibility that pain, anesthesia, surgical inflammation, and choice of painkillers could all potentially affect embryo transfer success – but not a word of any of this in the article.
This silence about pain and pain management raises a third concern – it establishes a record in the published literature that analgesics simply are not used for these surgeries. A sensible scientist looking to do a similar procedure would look at this literature and decide s/he would be a fool to use painkillers in their own mice.
Instead of blogging, I should be writing to journals (there are dozens of them) who leave this vital animal info, and these vital animals, out of their publications. This paper on mouse embryo transfers is typical, and certainly no worse than what’s standardly practiced. It caught my eye because I’m interested in that procedure (working with colleagues on assessing whether more aggressive pain management improves or worsens embryo survival in mice), not because it’s any worse than most published papers.
This is the letter I’ve written to “Human Reproduction.” I’ll post if I get a response, but it’s been a month, so I don’t expect one. Feel free to plagiarize it and write to a few journals yourself; this peeve of mine should be easy to fix. I’m not alone with this peeve; in fact, the National Academy of Sciences has a group working on developing guidelines for better publishing of animal studies.
“To the editor:
I call your attention to some important omissions in the Epub article “Dynamic microfunnel culture enhances mouse embryo development and pregnancy rates” by Heo et al (Hum Repro 2010 Jan 3).
In this article, the authors isolated zygotes from mouse oviducts with no mention of how they did this. Presumably it followed euthanasia of the mother, but important information -- such as method of euthanasia or time to collection of embryos -- that could affect the viability of the cells collected, is left unmentioned.
Later, embryos were “transferred to oviducts” of live mice, though with no mention or surgical anesthesia or peri-operative analgesia. Again, these important details that could affect the viability of the embryos (as might untreated surgical pain and inflammation) are left out of this report.
Leaving out such important details is poor science-writing. Live animals are complex; their pain, inflammation, drugs they’ve received and method of euthanasia can affect the biological behavior of the system under study and should be reported.
Moreover, there is a welfare concern in doing major survival surgery in laboratory mice. The corners cut in publication of an article such as this, leaving out mention of anesthesia and analgesia, creates the University of Michigan IACUC and your journal.
Sincerely, . . .”