|Darya Tourzani, 2nd Year
Program: Veterinary and Animal Sciences
Advisor: Pablo Visconti, PhD.
Education: University of Massachusetts, Amherst, BS, Animal Science 2016
I started my career in reproductive sciences in Dr. Pablo Visconti’s laboratory as an incoming third year undergraduate student. After graduating, I was accepted as a M.S. candidate in the Animal Biotechnology and Biomedical Sciences Graduate Program (ABBS) in the Fall of 2016. As part of my M.S., my investigations focused on how sperm acquire progressive motility after leaving the testis in the male reproductive tract. This process is known as epididymal maturation and occurs during the sperm’s transit from the proximal caput epididymis to the more distal cauda epididymis. As part of my studies, we studied how epididymal maturation affects signaling pathways and discovered that this process is accompanied by a decrease in O-GlcNAcylation and a concomitant increase in ser/thr phosphorylation. We hypothesized that the interplay between O-GlcNAcylation and phosphorylation is part of the mechanism by which sperm acquire progressive motility during their transit in the epididymis. These results were recently published (Tourzani et al., 2018, Frontiers in Cell and Developmental Biology) and I am preparing my second first-author manuscript reporting that isolation of caput epididymis by ligation mimics several signaling pathways occurring during epididymal maturation including a decrease in O-GlcNAcylation and an increase in ser/thr phosphorylation. Concluding my first year as M.S. candidate, in May 2017, I was selected to participate as a research facilitator for the Frontiers in Reproduction course at the Marine Biological Laboratories (MBL) in Woods Hole, Massachusetts. As part of this experience, I was able to observe and learn many assisted reproductive techniques (ART), including in vitro fertilization, intracellular sperm injection (ICSI) and embryo transfer. After rejoining the laboratory, Dr. Visconti and I talked about the possibility of changing from a M.S. to a Ph.D. degree and I was accepted as an ABBS Ph.D. candidate in January 2018. As part of my Ph.D. work, I started to be interested in the application of biotechnology to reproductive biology. Subfertility is a critical health problem with social and economic consequences. Since the first successful “Test-Tube” baby in 1978, over 5 million babies were born using ART. ART is used in humans and animals of economic relevance. In all species, despite their frequent use, ART methods are usually expensive, time consuming and have limited success depending the species. In all species, the limiting factor for successful pregnancies to occur is obtaining good quality preimplantation embryos which have a direct influence in implantation and pregnancy rates. My Ph.D. thesis is based on preliminary results indicating that manipulation of intracellular Ca2+ and of the metabolic profile of sperm increases their motility; and significantly improves success rates in fertilization, embryo development, embryonic quality and implantation rates in mouse models. The general translational objective of our group is to generate a new ART technology to be applied in IVF, ICSI and AI in humans and the breeding industry. Despite some advances in the Visconti’s group that make possible to achieve in vitro fertilization using sterile mouse sperm, the mechanisms by which Ca2+ and metabolic changes affect sperm fertilizing capacity are still not understood. As part of this fellowship, we will use mice models to test the hypothesis that there is a crosstalk between calcium and metabolism essential for the sperm to become fertile. We also hypothesize that manipulation of these pathways in vitro can be used to induce fertilizing capacity in subfertile or infertile sperm. In addition, we will test the hypothesis that in vitro treatment of sperm before combining them with the eggs previous to fertilization affects post-fertilization events that results in improving the embryo ability to get implanted in the uterus. To test these hypotheses we will use a battery of ART in combination with biochemical and molecular biology methods to analyze how sperm incubation conditions prior to fertilization regulate signaling pathways in sperm, and also how these conditions affect different stages of early embryo development. These experiments will be conducted in the Visconti laboratory in collaboration with Dr. Rafael Fissore and Dr. Jesse Mager from the Veterinary and Animal Science department. These approaches also have the potential to synergize interdisciplinary collaborations. As an example, I have been working with Dr. Juan Jimenez from XXXX to develop methods to study how sperm incubation conditions affect their ability to undergo chemotaxis using nanodevices. Finally, this project is also relevant from the translational and biotechnological points of view. In this respect, Dr. Visconti’s group has recently converted a provisional patent to improve ART in several mammalian species including humans. By improving sperm incubation conditions, these investigations have the potential to replace current standard media and to revolutionize ART worldwide.