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By Dave DeFusco

At the Katz School's Graduate Symposium on Science, Technology and Health, Tahereh Ghafoori and Rupali Khane, both ĐÔ°źÌìÌĂ in the M.S. in Biotechnology Management & Entrepreneurship, presented compelling research that could bring us closer to understanding male infertility, a condition that affects millions of couples worldwide.

Their project, “Studies of SUMO Protein and Spermatogenesis using Transgenic Mouse Models,” explored how a little-known protein, called SUMO, plays a major role in the complex biological process that creates sperm. Guided by their ĐÔ°źÌìÌĂmentors—Dr. Margarita Vigodner, professor of biology at the YU Stern College for Women, and Dr. Benjamin Lucas, lecturer at the Stern College for Women—the pair used genetically engineered mice to study what happens when this protein is turned off.

ĐÔ°źÌìÌĂ 8% to 12% of couples worldwide struggle with infertility, and in half of male cases, the cause remains unknown. That’s why research like Ghafoori and Khane’s is so important: it looks closely at spermatogenesis, the step-by-step process that transforms stem cells into mature sperm.

“Understanding how this process works—and what can go wrong—is key to solving the mystery behind many infertility cases,” said Dr. Vigodner. “Our lab focuses on how proteins are regulated during sperm development, especially through a process called SUMOylation.”

SUMOylation is a type of posttranslational modification, which means it’s a chemical change that happens to proteins after they’re made. SUMO stands for Small Ubiquitin-like Modifier, a molecule that attaches to other proteins and changes how they function.

“We already knew that SUMO proteins are active in the testicles and attach to many proteins involved in sperm production,” said Ghafoori. “But no one had fully explored what happens when you block this process in living animals.”

To study this, the team used transgenic mouse models—mice that had their genes altered in specific ways. They focused on the UBA2 gene, which helps launch the SUMOylation process. Using a tool called Cre-LoxP, they selectively turned off the gene in two different cell types:

• Stra8-Cre mice: SUMOylation was blocked in germ cells, which eventually become sperm.
• AMH-Cre mice: SUMOylation was blocked in Sertoli cells, which support and nourish developing sperm.

“This allowed us to test the importance of SUMOylation in both types of cells involved in spermatogenesis,” said Khane.

The results were dramatic. Male mice in both groups were completely infertile and showed major problems in testicular development. In Stra8-Cre mice, sperm development stalled at the early spermatocyte stage before sperm cells could mature. In AMH-Cre mice, the testicles gradually shrank, and the support system for sperm cells began to break down. 

Microscopic analysis confirmed a severe drop in sperm production. In fact, no sperm were found in the epididymis—the part of the male reproductive system where sperm mature and are stored. Even more telling, the testicular weight in Stra8-Cre mice dropped by 50%, and in AMH-Cre mice by a stunning 75% even though their overall body weight stayed the same.

To figure out why this was happening, the team used single-cell RNA sequencing, a technique that allows scientists to study which genes are turned on or off in individual cells.

“We discovered that genes necessary for the later stages of sperm development were significantly turned down,” said Ghafoori. “Meanwhile, genes linked to inflammation and stress were turned up. That suggests that blocking SUMOylation disrupts the normal balance in the testis and activates damage-control responses.”

This work offers strong evidence that SUMOylation is not just a background player—it’s essential for healthy sperm development.

“Without it, meiosis stalls, the testicular structure breaks down and infertility results,” said Dr. Vigodner. “This is a big step forward in identifying molecular targets that could one day lead to new treatments for male infertility.”