Reproductive toxicology accounts for a decent percentage of the research represented at the Society for the Study of Reproduction meeting wrapping up today in Kona, HI. Most of this has been directed at estrogen mimetics and assorted endocrine disrupters like Bisphenol A, the chemical in polycarbonate plastic that’s has many ditching their Nalgene water bottles. Many of these are ubiquitous chemicals that we come in contact with, but don’t intentionally ingest. So, I was a bit surprised to see a poster on glucosamine, a dietary supplement that many take for joint health. I met Jeremy Thompson today who with his group in the University of Adelaide, has been amassing evidence putting him on the wrong side of the supplement industry in Australia. Cheryl Schelbach in his lab has been presenting data on birth defects caused by the supplement. Glucosamine is an amino sugar that interferes with glucose energy sensing pathways by bypassing the rate limiting step in hexosamine biosynthesis. Some studies indicated that the supplement seems safe if taken during pregnancy, not a lot of data exists as to whether it’s useful or not. Schelbach injected glucosamine into the stomachs of mice right around the time of conception. To see if there were synergistic effects with a diet that might induce hyperglycemia, she used groups of mice raised on high fat and low fat diets. The big result according to Thompson, who was presenting the poster in Cheryl’s absence, is that 45% of mice (9 out of 20) administered glucosmaine (with the low fat diet) had abnormal fetuses compared to none in the low fat, glucosamine free regimen. High fat diet alone led to 25% abnormal pregnancy. Adding glucosamine to the high fat diet didn’t elevate the effect. Thompson says they think the diet primed the mice to a high glycemic index in such a way that the glucosamine had little effect. While recognizing that their study had limitations, they thought it prudent to release their findings to the media prior to publishing them in a peer reviewed journal. And they offered a mild warning that women looking to become pregnant might want to avoid the supplement. Apparently the industry reaction was vitriolic. “The hostility we experienced was profound,” Thompson told me.

Just as recent metagenomic studies have demonstrated vast information about the bacteria that teem in and around us, there is a deep, mysterious well of ancient infections within our genomes Alexei Evsikov from Jackson Labs spoke this morning about the activity of so-called LTR retrotranposons during early embryonic development in mice. LTR retrotransposons are essentially viral remnants that have camped out at various places in the genome sometimes landing in areas that break up genes and sometimes brining promoter regions in close proximity to genes that would have otherwise gone unexpressed. Evsikov presented studies suggesting that these transposons become actively expressed and may even be working to intercalate themselves into new areas of the genome during the crucial developmental period when genes from sperm and egg meet to form a new genome of a new living creature. The brilliance of this strategy from the transposon’s perspective is that it would be one of the best ways to secure its place in the germline of the new individual. Equally brilliant, however, is the fact that the mouse embryo seems to use the activity of these infectious elements to drive the expression of certain genes needed for development. If you turn off the cellular machinery necessary for these retrotransposons to do their thing, it spells disaster for the embryo. The viral-like elements can have bad effects, of course. You don’t want genetic elements, especially elements with promoters jumping about your genome willy nilly, but as always with biology it’s a careful balance. His ideas met with a bit of scepticism, but Evsikov says, “I just speculate that we have to change our thinking about retrotranpsons being the ultimate parasites, to being … actually an extremely good source of variation.”

Some things make reproductive biology really come alive. Take today: someone handed me a horse vagina while I was walking through this morning’s poster session at the Society for the Study of Reproduction meeting in Kona HI. To be precise, it was the vagina, cervix, uterus, ovaries, and part of the bladder of a mare from a Spanish slaughterhouse. Rafael Latorre was presenting a project underway for at least sixteen years at the University of Murcia, Spain to build anatomy education resources using plastination. You might recognize the process as that popularized by Body World exhibits. Developed by Gunter von Hagens, it involves dehydrating tissue samples and replacing the fluids with various polymers to retain a lifelike look and preserve it for years to come. The group at Murcia has prepared as many as 600 specimens according to Latorre. The massive equine reproductive tract in my hands was made with modifications to the process to give it a rubbery, malleable feel, and windows were cut out so that the insides could be viewed in all their glory. “Did they give you any problems with this thing in your luggage?” asked Kenneth Campbell from University of Massachuestts-Boston. “No,” replied Latorre. He had a gaggle of conference-goers asking questions, though.

Akiko Yabuuchi from George Daley’s lab at Children’s Hospital of Boston reported on using somatic cell nuclear transfer to reprogram human nuclei (Daley’s in fact) in bovine egg cells at the Society for the Study of Reproduction meeting in Kona, today. Interspecies nuclear transfer is highly controversial, so it wasn’t exactly surprising that one of Yabuuchi’s first slides mentioned that the project has approval from the Institutional Review Boards and Embryonic Stem Cell Research Oversight committees at Brigham and Women’s and Children’s Hospital where the work was carried out. The efficiency wasn’t very high, but the hybrid embryos were able to undergo cleavage and correct segregation of the human chromosomes. Several made it to the 16-cell stage, but none survived past that. The goal was not implantation or pregnancy, of course, but to monitor development in these hybrid embryos and see if they could potentially lead to embryonic stem cell lines. The project includes tests to see whether extract from human embryonic cells will provide some of the necessary materials to allow normal nuclear reprogramming in the foreign egg environment. Yabuuchi in her acknowledgement said Daley was a great boss for, among other things, providing the skin cells they were using as nuclei donors.

This wasn’t the first instance of interspecies cloning I heard about today. So-Gun Hong from Seol National University was performing interspecies somatic cell nuclear transfer with dog nuclei and bovine egg cells. It’s preliminary work, with little success so far. The interspecies nuclear transfer experiments are ancillary to a project to simply create a transgenic dog expressing GFP using somatic cell nuclear transfer into dog egg cells, but these eggs are notoriously hard to come by. No luck in getting a live birth yet, according to So-Gun.

In one of the stranger incidences of hybrid cloning talked about today, Sandra Lencka-Ostrowaska from the Institute of Genetics and Animal Breeding of the Polish Academy of Sciences in Jastrzebiec, Poland presented her work using mouse eggs to try and reprogram the nuclei of Clethrionomys glareolus, the bank vole. The reason? Generating interspecies hybrids may provide ways to study species specific nuclear reprogramming. The technical challenges in nuclear reprogramming using egg cells remain despite the tremendous advances of Shinya Yamanaka and others with so-called induced pluripotent stem cells. The work continues and it will be interesting to see what happens next.

The Society for the Study of Reproduction meeting in Kona, HI sports an eclectic mix of talks and posters — so eclectic, in fact, that I’ve regularly found myself asking just what many of the talks have to do with reproduction. The keynote address for example by Evan Simpson of Prince Henry’s Institute of Medical Research, Monash Medical Center in Australia covered his lab’s amazing work linking metabolic dysregulation, obesity, aging, and cancer. Nope, no reproduction there, except for the role of circulating androgens. Simpson laid out a career devoted to aromatase and the ways in which changes in estrogen signalling contribute to breast cancer. Fascinating stuff, but even he was a bit stymied by the link to cancer.

Other talks on cell fate determination, entire sessions devoted to stem cell biology, and more talks and posters still to come on environmental toxicology leave me wondering what exactly this society is all about. I asked Doug Stocco, the current president of SSR what exactly gives and he told me about how SSR had in the past built a strong base of livestock reproductive researchers (these are the folks “with the brown rings around their biceps,” he joked) and then saw an influx of molecular people and mouse jockeys. For his part, Stocco studies steroids and sperm in mice. The wish has always been to build membership and camradarie rather than pare back to a party base, so the current mix has people who work in animals from cows to bank voles and several strange models in between.

Just to put a fine point on it, there were two short back to back talks on ferrets. Xingshen Sun from the University of Iowa was using viral gene targeting and nuclear transfer to create a CFTR knockout version of a domestic ferret. By deleting portion of the CFTR gene, these ferrets could be a good model for cystic fibrosis. The very next talk featured Rachel Santymire, of Lincoln Park Zoo in Chicago, IL, who is working with the Smithsonian Institution National Zoological Park to maintain the U.S. population of black footed ferrets, reportedly one of the most endangered mammals in North America. As part of her conservation work, she compared several different sperm freezing techniques for both domestic ferrets and black footed ferrets. The domestics did better on all counts, but it sounds as if the little swimmers from the black footed ferrets are starting from a disadvantage. The fact the project Santymire works with has produced thousands of ferrets from just seven rescued in the 1980s wouldn’t seem to bode well for their reproductive health. Although says Santymire, the breeding program and who mates with who is very well managed. More likely, she says, changes to the diets for captive ferrets might have caused problems. They eat prairie dogs almost exclusively in the wild.

Yesterday afternoon marked the start of the Society for the Study of Reproduction 2008, a 1,000 attendee meeting held this year in Kona, Hawaii. It’s a beautiful place for a meeting on sex, to be sure, but looking at these videos of the 1959 eruption of Kilauea, I became just a little less confident about the status of a vent that recently began spewing toxic sulphur dioxide across much of the island state (and leaving the Konaa bit smoggy-or in the local parlance “voggy”). But volcanoes are all about rebirth of the living rock, a fitting setting for reproduction, and the people on what’s commonly known as the big island have mustered the fortitude to stick around on an active volcano for generations. To prove to myself that I had the same, I took a stroll across what was that molten lake only 50 years ago. It’s still steaming hot and only two miles from the vent that opened up this spring.

I’ll be reporting back soon on what has already shown itself to be an ecclectic mix of talks.