John McCracken

John McCracken

This story may have caught your attention a few months ago: in October 2014, the first human baby was born from a transplanted uterus. The procedure, conducted by Mats Brännström from the University of Gothenburg in Sweden, builds on decades of research on uterine transplantation and the role of the uterus in animal reproductive cycles. John McCracken, professor in residence in the Department of Animal Science, was one of a few scientists who were major contributors to Brännström’s research. McCracken, who has performed animal uterine research for more than forty years, studies hormonal transfer between the uterus and ovary in mammals and is an expert in ovarian and uterine transplants in sheep. In 2005, the two collaborated at UConn to study and perfect the model of sheep uterine transplantation, which was one of the critical last steps leading Brännström to perform a human procedure.

Before coming to UConn, McCracken was a principal scientist at the Worcester Foundation, a now discontinued biomedical research institute in Shrewsbury, Massachusetts. He earned his bachelor’s degree in veterinary medicine and surgery and his PhD from the University of Glasgow in Scotland. He is a member of the Royal College of Veterinary Surgeons in London. In 1998, he was appointed professor in residence in the Department of Animal Science.

In order to understand McCracken’s role in Brännström’s work, one has to start in the 1970s, when McCracken began his research on the the hormonal mechanisms that control the degradation of the corpus luteum (CL), a bright-yellowish cellular structure in the ovary that secretes progesterone, a hormone that maintains pregnancy after an egg is fertilized. If fertilization does not occur, the CL degrades, or regresses, which reduces progesterone and allows a new egg to develop for fertilization. CL regression is essentially the restart button of the estrous cycle in animals and the menstrual cycle in primates. But what causes the CL to regress (i.e., what pushes the button) was still somewhat of a mystery before McCracken’s research.

At the time, it was speculated that a hormone known as PGF2α, which was secreted by the uterus of domestic animals, was responsible for triggering CL regression. The speculation was controversial since many researchers believed that hormones could not move directly from uterus to ovary. With other scientists at the Worcester Foundation, McCracken performed several ovarian and uterine transplants on sheep to study whether a uterine-born hormone really could trigger CL regression, the cycle restart. During the transplants, McCracken found that as long as the ovary and uterus remained together, even when both structures were transplanted with vascular connections to a separate location in sheep, the CL regressed normally. In other words, in order for the reproductive cycle to restart in sheep, “the uterus and ovary had to be in close contact.”

In 1972, McCracken and his collaborators confirmed that PGF2α was the cause of CL regression in domestic animals. Leading up to this discovery, McCracken gained considerable expertise on utero-ovarian interactions and his work gave him the opportunity to more closely study uterine and ovarian transplantation. His skill set and knowledge base made him the perfect candidate to work with Brännström in developing a model for human uterine transplantation.

In 1998, McCracken was appointed at UConn, where he continued to study interactions between the uterus and ovary. “By this time, I had developed all these models of sheep uterine transplantation. So I brought my animal models down here [from the Worcester Foundation].” In 2005, McCracken met Brännström, who told him that his long-term goal was to transplant the human uterus and asked if might he come to UConn to see how McCracken performed uterine transplants in sheep. Working at UConn in 2006, the two performed several uterine transplants in sheep. The goal was to develop a procedure that would approximate a human uterine transplant as closely as possible. McCracken had already performed dozens of uterine transplants in sheep, but none that adequately resembled a human procedure.

By practicing transplantation on sheep (who have uteruses similar in size to those of humans) and by implementing techniques that one would perform in a human uterine transplant, McCracken and Brännström could develop a model that would be useful for a human procedure. Among other procedures, they needed to raise the kidney to get easier access to the pelvis. To do this, “we put a kidney rest in and we tilted the body so that the viscera [the body’s internal organs] moved away from the pelvis” in order to expose the uterus. The transplants were, on all counts, successful. Later in 2006, McCracken was invited to Sweden to perform three more sheep uterine transplants with Brännström. These were “slightly different. . . . We took the uterus out of the sheep, flushed it with anticoagulants and placed it in cold saline for one hour,” which would preserve the organ before transplantation and be necessary in a human procedure. In all cases, after the transplantation, blood flowed back into the uterus at a normal rate. Brännström used what he learned from the sheep model to conduct a uterine transplantation in the baboon, and eventually, in the human.

McCracken is modest about his contributions but recognizes the importance of his research on the role of the uterus in the reproductive cycle and his expertise on uterine transplantation. “It’s a natural progression,” says McCracken, referring to how uterine transplants have evolved. “These things don’t happen overnight. . . . One step led to another. It took a few years to get” to the human procedure. For Brännström and for McCracken—who is still making important discoveries relating to the hormones that stimulate PGF2α production and CL regression—the research does not end here.

By Michael Clausen