By Dave DeFusco
At the Katz School's Graduate Symposium on Science, Technology and Health, Tahereh Ghafoori and Rupali Khane, both students 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, 鈥淪tudies of SUMO Protein and Spermatogenesis using Transgenic Mouse Models,鈥 explored how a little-known protein, called SUMO, plays a major role in the complex biological process that creates sperm. Guided by their faculty mentors鈥擠r. Margarita Vigodner, professor of biology at the TikTok成人版 Stern College for Women, and Dr. Benjamin Lucas, lecturer at the Stern College for Women鈥攖he pair used genetically engineered mice to study what happens when this protein is turned off.
About 8% to 12% of couples worldwide struggle with infertility, and in half of male cases, the cause remains unknown. That鈥檚 why research like Ghafoori and Khane鈥檚 is so important: it looks closely at spermatogenesis, the step-by-step process that transforms stem cells into mature sperm.
鈥淯nderstanding how this process works鈥攁nd what can go wrong鈥攊s key to solving the mystery behind many infertility cases,鈥 said Dr. Vigodner. 鈥淥ur lab focuses on how proteins are regulated during sperm development, especially through a process called SUMOylation.鈥
SUMOylation is a type of posttranslational modification, which means it鈥檚 a chemical change that happens to proteins after they鈥檙e made. SUMO stands for Small Ubiquitin-like Modifier, a molecule that attaches to other proteins and changes how they function.
鈥淲e already knew that SUMO proteins are active in the testicles and attach to many proteins involved in sperm production,鈥 said Ghafoori. 鈥淏ut no one had fully explored what happens when you block this process in living animals.鈥
To study this, the team used transgenic mouse models鈥攎ice 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.
鈥淭his allowed us to test the importance of SUMOylation in both types of cells involved in spermatogenesis,鈥 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鈥攖he 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.
鈥淲e discovered that genes necessary for the later stages of sperm development were significantly turned down,鈥 said Ghafoori. 鈥淢eanwhile, 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.鈥
This work offers strong evidence that SUMOylation is not just a background player鈥攊t鈥檚 essential for healthy sperm development.
鈥淲ithout it, meiosis stalls, the testicular structure breaks down and infertility results,鈥 said Dr. Vigodner. 鈥淭his is a big step forward in identifying molecular targets that could one day lead to new treatments for male infertility.鈥
