Rocío Rivera is closing in on the cause of an ‘overgrowth’ syndrome.
By Anita Neal Harrison
The first time she saw a calf with “large-offspring syndrome,” Rocío Rivera was working as a full-time lab tech at the University of Florida, where she was also earning a doctorate in reproductive physiology. She had helped produce the calf using in vitro fertilization; the goal was to preserve genes from a prize dairy cow. But the calf was twice the normal size and so heavy it could not stand.
For the week the calf lived, Rivera looked at it and thought, “I made this happen” — the syndrome only affects calves produced with assisted reproductive technologies — but neither she, nor anyone else, knew exactly what caused the overgrowth. “I became fascinated by this syndrome,” she says. “I wanted to understand, ‘What is it that we are doing with these procedures that is causing this to happen?’”
Rivera is today an associate professor in animal sciences at MU, where, she says, her research includes using large-offspring syndrome studies as a model to better understand Beckwith-Wiedemann, a similar condition that affects humans.
This spring, she, her students and her faculty collaborators at MU’s Animal Science Research Center identified several genes involved in large-offspring syndrome; genes that, in the parlance of geneticists, suffer from a “misregulation of their expression.” The discovery, published in the Proceedings of the National Academy of Sciences, is important because it shows previously unknown “epigenetic” alterations in large-offspring syndrome. Such epigenetic findings involve the collection of chemical compounds and regulators that determines when and where genes are expressed.
Think of it as the difference between notes and music, says Rivera, a lifelong musician who plays viola with the Columbia Civic Orchestra. “If you have all of the notes but nothing else, that would sound like nothing,” she says. “But if you add the dynamics, the key and all the musical symbols, then all of a sudden you have music. That’s how I see the DNA, which would be just the notes, and then the epigenome, which is what makes the music happen.”
Rivera began exploring the connection between the epigenome and assisted reproduction during a three-year post-doctoral stint at the University of Pennsylvania. Her work there was split between two labs: a familiar reproduction lab and an epigenetics lab, which was new territory for her.
“I was a little scared because I was a physiologist, not a molecular biologist,” she says. “But I dove right in, and it was very exciting.”
At UPenn she was tasked with researching “genomic imprinting,” one type of epigenetic mechanism in mammals. Mammals inherit two copies of their genes — one from their mother and one from their father. Typically both copies are expressed. But in a small number of genes, one or the other has a chemical tag that acts as an “off” switch, silencing it.
Rivera’s research helps show that proper genomic imprinting is crucial to fetal growth and development. When the epigenetic mechanism goes wrong, the result can lead to serious problems. Babies with Beckwith-Wiedemann syndrome, for example, grow and gain weight more rapidly than normal in the womb and throughout early childhood. Many have enlarged tongues, abdominal wall defects and asymmetric growth, all of which also occur in large-offspring syndrome. Beckwith-Wiedemann also raises children’s risk for cancer.
Although the syndrome can occur naturally, its incidence rate increases in children conceived through assisted-reproductive technologies. That made Rivera wonder how it might be related to large-offspring syndrome. For the seven-and-a-half years Rivera has been at MU, she and her students have been exploring that question. In 2013, her laboratory published research showing that large-offspring syndrome has loss-of-imprinting on genes also known to be misregulated in Beckwith-Wiedemann — an important finding because the molecular similarity means large-offspring syndrome can serve as a model for investigating the causes of Beckwith-Wiedemann.
“By identifying the large-offspring syndrome genes, we can take steps toward discovering which genes cause [Beckwith-Wiedemann syndrome] in humans,” Rivera says. Thus far, Rivera and her students have identified around 100 imprinted genes in cattle. That leaves many more genes to explore.
It’s slow, tedious work, but Rivera is undaunted. This opportunity for discovery is, after all, why she switched career paths from veterinary medicine to lab research. Once she entered a lab for the first time, she recalls: “That was it for me. I didn’t realize this field existed and that people actually work in it and run experiments and test hypotheses; I was fascinated.”
And she still is. “To find things that nobody has ever known before, it’s exciting,” she says. “And quite fun.”