The Earth is undergoing an unnatural sixth mass extinction event that is disrupting balanced and interconnected ecosystems and endangering human survival. Any time a species seems like a good candidate for laboratory research, therefore, it’s important to check its conservation status.
According to the International Union for the Conservation of Nature, the naked mole-rat (Heterocephalus glaber), also called the sand puppy, is a species of “Least Concern.”
That’s good news for Dr. Miguel Angel Brieño-Enríquez, who for several years has been studying naked mole-rats — NMR — in his lab at the Magee-Womens Research Institute & Foundation in Pittsburgh and, before there, at Cornell University in Ithaca, New York.
The NMR is considered to be “a model in ovarian development and reproductive aging.”
Brieño-Enríquez will give a talk titled “Ovarian Aging and Its Effects Across the Lifespan” at 4 p.m. today at the CWC House, as part of the Chautauqua Women’s Club’s new Chautauqua Academy programming.
At the University of Pittsburgh School of Medicine, he is an assistant professor in the Department of Obstetrics, Gynecology and Reproductive Sciences. He is also an associated member of the University of Pittsburgh’s Aging Institute and its Genome Stability Program at the UPMC Hillman Cancer Center.
On his Magee-Womens webpage Brieño-Enríquez wrote, “My lab and I are researching how we can reduce ovarian aging (and) keep women’s eggs healthy throughout their lives, so they can continue having healthy babies and improve their healthspan and lifespan.”
Unlike in the NMR, more than 50% of a human female’s eggs die prior to birth. For the rest of her life, the number of healthy eggs in her ovaries will continue to diminish.
According to Brieño-Enríquez, “ovarian aging affects everything from cancer risk to heart health to longevity, (so) understanding ovarian health matters even long after childbearing years have passed.”
As a child growing up in Mexico, “I did always want to be a doctor,” he said. “… Back in the day, I always wanted to play with the chemistry set.” In 1996, when he enrolled in medical school at Universidad Autónoma de San Luis Potosí in Mexico to study for both his bachelor’s in medicine and his Doctor of Medicine, Brieño-Enríquez thought he’d become a plastic surgeon. Along the way, he “decided it’s not always about beauty” and chose instead “to work with moms and babies.”
He continued, “My mom had a lot of sisters. She had 10 siblings and six are female. My dad had eight siblings and five are females. My mom had me when she was 35, so she was an aged mom. A lot of my family had children late in life. I grew up in a family with a lot of powerful women.”
At Universidad Autónoma de San Luis Potosí, Brieño-Enríquez also earned his master’s in biomedical sciences in 2006. Then he went to Barcelona to work with human cells, rather than to begin a medical residency program.
“My family is of Spanish heritage,” he said. “I went to Spain with a lot of hope, joy and two suitcases. In Spain and Belgium at that time, there weren’t laws to prevent (working with human cells).”
While earning his master’s and his Doctor of Philosophy in cell biology at the Medicine School, Universitat Autònoma de Barcelona (2006–2011), Brieño-Enríquez studied Bisphenol A. The chemical compound BPA is mainly used in the manufacture of plastics on an industrial scale.
“BPA and microplastics were affecting human cells,” he said.
Brieño-Enríquez served as first author of a scholarly research paper and article published in the Oxford Academic journal, Human Reproduction: “Human meiotic progression and recombination are affected by Bisphenol A exposure during in vitro human oocyte development.” Its abstract concluded as follows, “BPA can modify the gene expression pattern, which may explain the effects of BPA on female germ cells.”
His “first paper was the (very) first analysis on BPA in human samples,” Brieño-Enríquez said.
The second paper for which he was the lead author was published in Molecular Human Reproduction: “Gene expression is altered after bisphenol A exposure in human fetal oocytes in vitro,” published in 2012.
From Barcelona, Brieño-Enríquez moved to Madrid in January 2012 to work for two years as a postdoctoral research scholar on “environmental factors” at the Center for Biological Investigations at Spain’s National Council of Science and Technology (Consejo Superior de Investigaciones Científicas).
“Vinclozolin is a fungicide sprayed on grapes,” he said. “We eat a lot of it when we drink wine, even in Europe. It has affected not only women but also their babies. I did a transgenerational study on rats and mice.”
According to Brieño-Enríquez, the effects of the 2008 global financial crisis were still being felt in Europe in 2014, and “funding was really bad,” so although he was very happy in Madrid, he moved to Ithaca to work as a postdoctoral research scholar at the Center for Reproductive Genomics at Cornell.
He said his first two years were funded by a professor. Then the U.S. National Institutes of Health awarded him a three-year grant enabling him to start and run his own lab.
“(The NIH grant) was to develop (my) career as an independent researcher,” Brieño-Enríquez said. “It was one of the few grants a non-U.S. citizen could apply for.”
And it has succeeded beyond expectations.
“Suddenly one night — it was 6 p.m. on a Friday — a professor at Cornell had samples of the naked mole-rat,” Brieño-Enríquez said. “I didn’t know what it was. I googled it and said, ‘Oh my gosh, these animals are so ugly.’ Their ovaries didn’t look like (those of) any other animals. They looked like human ovaries, but they don’t age.”
He continued, “That was the luckiest situation in my life because it changed my life. I could tease apart how these mole-rats can have babies for life and how we can make (someone) feel like a 30-year-old lady when they’re 60.”
Although initially he planned to return to Spain in 2019, Brieño-Enríquez realized that to continue his research — using “one of the ugliest animals in the world for good” — he needed “a big network with a hospital and a university, access to clinicians and a population, a big focus on women’s health and a city without the issues of a massive city.”
Magee-Womens Research Institute and the University of Pittsburgh met each of his needs.
“I wanted to be a doctor, but I’m not,” Brieño-Enríquez said. “… Sometimes the stars and moon align. They were edgy enough to put their money on me and say, ‘This person with a funny animal is thinking outside the box.’ ”
Looking forward, “the big picture is to create new compounds to extend the ovarian lifespan. We are creating (them) based on what we’re learning from the little animal.”
The consequences of pregnancy are “like a black box,” Brieño-Enríquez said. “There’s a massive hole. I really want to find how it works. That’s not just helping your patients but (also) women — who are more than half of the population.”
