Environmental Factor

Environmental Factor

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November 2017

Basic science behind male reproduction takes center stage

The basic science behind male reproduction and fertility took center stage Oct. 13 at a symposium sponsored by NIEHS and the Campion Fund. Humphrey Yao, Ph.D., head of the NIEHS Reproductive Developmental Biology Group, partnered with Phyllis Leppert, M.D., Ph.D., co-founder of the Campion Fund (see sidebar), to host the meeting.

The symposium covered the medical aspects of fertility, basic science of different cell types, and the role of environmental exposures. Two keynote speakers, eight talks, and a poster session presented attendees with the latest research on these varied topics.

Yao, right, and Leppert Yao, right, and Leppert set a warm, collegial tone for the day-long meeting. (Photo courtesy of Steve McCaw)

Novel function for certain RNAs

Haifan Lin Lin’s work sheds light on portions of DNA sometimes called junk DNA. “I prefer to call it terra incognita,” he said. (Photo courtesy of Steve McCaw)

Keynote speaker Haifan Lin, Ph.D., from Yale University, kicked off the day’s presentations by exploring the epigenetic function in mammals of a type of RNA called piRNA. Epigenetics refers to heritable changes to a gene that alter its function without changing the underlying sequence of its DNA.

The Lin lab studied whether piRNA facilitates the epigenetic change known as methylation through involvement in a complex that guides RNA to chromatin, rather than to DNA itself. Chromatin is a complex of DNA and proteins that compresses DNA to form chromosomes.

“We think we have found a major mechanism that is very important for guiding epigenetic factors to their target sites,” Lin said, describing his unpublished findings.

Search for a male contraceptive

Martin Matzuk “CRISPR is a game-changer for us,” Matzuk said of the gene editing technology. (Photo courtesy of Steve McCaw)

The search for male contraceptives was the focus of the keynote talk by Martin Matzuk, M.D., Ph.D., from Baylor College of Medicine in Houston. Matzuk and colleagues identified a gene product necessary for male fertility by using animal models, CRISPR-Cas9 gene editing technology, and in vitro screening methods.

They are now screening billions of molecules to find substances that target the gene product as candidates for a male contraceptive. A technology known as DNA barcoding allows screening of up to 2 billion molecules in a single mixture, he explained.

“This entire project came to be because of Franco,” Matzuk said, referring to Francesco DeMayo, Ph.D., who came to NIEHS from Baylor in 2015 to lead the institute’s Pregnancy and Female Reproduction Group. DeMayo now leads the NIEHS Reproductive and Developmental Biology Laboratory.

Experts’ research updates

Barbara Nicol Barbara Nicol, Ph.D., a visiting fellow in Yao’s lab, discussed her research during the poster session. Yao said hard work by all his lab members helped make the meeting a success. (Photo courtesy of Steve McCaw)

Connections between the research questions pursued by various attendees were underscored during discussion times, as postdoctoral fellows confirmed insights with lead researchers, and scientists asked advice of each other regarding new techniques and next steps.

Yao described the lineup of experts as the field’s A-list. The speakers and their current projects are presented below.

Janice Bailey, Ph.D., Laval University, Canada — How methylation of sperm DNA, from paternal exposure to persistent organic pollutants, influences health effects in offspring, and the therapeutic value of folic acid supplements.

Tracy Bale, Ph.D., University of Maryland — A novel mechanism by which the environment, including stress, diet, drugs, and toxins, can regulate epigenetic marks in sperm.

Blanche Capel, Ph.D., Duke University — Regulation of gene transcription in the poorly understood cell cycle of male gonocytes, and implications for fertility and tumor formation.

Matt Coward, M.D., University of North Carolina at Chapel Hill — Approaches to evaluating and treating male fertility problems in couples experiencing infertility.

Tony DeFalco, Ph.D., Cincinnati Children’s Hospital Medical Center — How the system of blood vessels, or vasculature, in the fetal testis regulates differentiation of Leydig cells.

Jannette Dufour, Ph.D., Texas Tech University — The potential for cell-based gene therapy using Sertoli cells, which help protect male germ cells from immune attack.

Christopher Geyer, Ph.D., East Carolina University — Uncovering molecular controls by which retinoic acid drives cell differentiation early in the cell cycle that produces mature sperm.

Debra Wolgemuth, Ph.D., Columbia University — Effects of alterations in a protein called BRDT on the development of spermatocytes and spermatids, and ultimately, male fertility.


Blanche Capel Capel was Yao’s postdoctoral mentor, she said, highlighting the sometimes small world of scientific research. (Photo courtesy of Steve McCaw)
Fei Zhao discusses research Fei Zhao, Ph.D., a visiting fellow in Yao’s lab, discussed the research that led to his groundbreaking research paper published in Science in September. (Photo courtesy of Steve McCaw)
Tony DeFalco DeFalco studies disorders of sexual development, and the genetic and molecular mechanisms that underlie embryonic differentiation and organ development. (Photo courtesy of Steve McCaw)
Emmi Rotgers Emmi Rotgers, M.D., Ph.D., a visiting fellow in Yao’s lab, shared research on steroid hormones and the mechanisms that underlie infertility and obesity. (Photo courtesy of Steve McCaw)
Chris Geyer Geyer, a former postdoctoral fellow at NIEHS, researches mechanisms behind mammalian germ cell development. (Photo courtesy of Steve McCaw)
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