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Item Hyaluronidase 6 Does Not Affect Cumulus-Oocyte Complex Dispersal and Male Mice Fertility(MDPI, 2022-04-25) Bang, Hyewon; Lee, Sujin; Jeong, Pil-Soo; Seol, Dong-Won; Son, Daeun; Kim, Young-Hyun; Song, Bong-Seok; Sim, Bo-Woong; Park, Soojin; Lee, Dong-Mok; Wee, Gabbine; Park, Joon-Suk; Kim, Sun-Uk; Kim, Ekyune; Biochemistry and Molecular Biology, School of MedicineGlycosylphosphatidylinositol-anchored sperm hyaluronidases (HYAL) assist sperm penetration through the cumulus-oocyte complex (COC), but their role in mammalian fertilization remains unclear. Previously, we demonstrated that sperm from HYAL 5 and 7 double-knockout (dKO) mice produced significantly less offspring than sperm from wild-type mice due to defective COC dispersal. However, the HYAL6 gene remained active in the sperm from the dKO mice, indicating that they were not entirely infertile. This study explored the role of HYAL6 in fertilization by analyzing HYAL6-mutant mice. In this mouse model, HYAL5 and HYAL7 were present in the HYAL6-knockout sperm, and they could disperse hyaluronic acid. We found that HYAL6 was present on the surface of sperm. However, male mice lacking the HYAL6 gene had normal fertility, testicular integrity, and sperm characteristics. Furthermore, in vitro fertilization assays demonstrated that HYAL6-deficient epididymal sperm functioned normally. Therefore, HYAL6 is dispensable for fertilization.Item Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness(Springer, 2022) Mainali, Shraddha; Aiyagari, Venkatesh; Alexander, Sheila; Bodien, Yelena; Boerwinkle, Varina; Boly, Melanie; Brown, Emery; Brown, Jeremy; Claassen, Jan; Edlow, Brian L.; Fink, Ericka L.; Fins, Joseph J.; Foreman, Brandon; Frontera, Jennifer; Geocadin, Romergryko G.; Giacino, Joseph; Gilmore, Emily J.; Gosseries, Olivia; Hammond, Flora; Helbok, Raimund; Hemphill, J. Claude; Hirsch, Karen; Kim, Keri; Laureys, Steven; Lewis, Ariane; Ling, Geoffrey; Livesay, Sarah L.; McCredie, Victoria; McNett, Molly; Menon, David; Molteni, Erika; Olson, DaiWai; O’Phelan, Kristine; Park, Soojin; Polizzotto, Len; Provencio, Jose Javier; Puybasset, Louis; Venkatasubba Rao, Chethan P.; Robertson, Courtney; Rohaut, Benjamin; Rubin, Michael; Sharshar, Tarek; Shutter, Lori; Silva, Gisele Sampaio; Smith, Wade; Steven, Robert D.; Thibaut, Aurore; Vespa, Paul; Wagner, Amy K.; Ziai, Wendy C.; Zink, Elizabeth; Suarez, Jose I.; Physical Medicine and Rehabilitation, School of MedicineThis proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.Item Sperm hyaluronidase is critical to mammals' fertilization for its ability to disperse cumulus-oocyte complex layer(Wolters Kluwer, 2022) Seol, Dong-Won; Joo, Sang Hoon; Kim, Young-Hyun; Song, Bong-Seok; Sim, Bo-Woong; Kim, Sun-Uk; Park, Soojin; Wee, Gabbine; Kim, Ekyune; Biochemistry and Molecular Biology, School of MedicineGlycosylphosphatidylinositol-anchored sperm hyaluronidases have long been believed to assist in sperm penetration through the cumulus-oocyte complex (COC); however, their role in mammalian fertilization remains unclear. Previously, we have shown that hyaluronidase 5 (Hyal5)/Hyal7 double-knockout (dKO) mice produce significantly fewer offspring than their wild-type (WT) counterparts because of defective COC dispersal. Male infertility is mainly caused by a low sperm count. It can be further exacerbated by the deficiency of sperm hyaluronidase, which disperses the cumulus cells of the outer layer of the COC. In the current study, we evaluated the effects of a low count of Hyal-deficient sperm and conditions of ovulated oocytes on the fertilization rate using a mouse model. Our results demonstrated that a low sperm count further decreases the in vitro fertilization (IVF) rate of Hyal-deficient dKO spermatozoa. In addition, the dKO spermatozoa resulted in a fertilization rate of 12.5% upon fertilizing COCs with a thick cumulus layer, whereas the IVF rate was comparable to that of WT spermatozoa when oocytes with a thin or no cumulus layer were fertilized. Finally, we proved that the IVF rate of dKO spermatozoa could be recovered by adding rat spermatozoa as a source of sperm hyal. Our results suggest that a deficiency of proteins involved in fertilization, such as sperm hyal, has a vital role in fertilization.Item Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models(Frontiers Media, 2024-01-08) Ma, Xin; Botros, Andro; Yun, Sylvia R.; Park, Eun Young; Kim, Olga; Park, Soojin; Pham, Thu-Huyen; Chen, Ruihong; Palaniappan, Murugesan; Matzuk, Martin M.; Kim, Jaeyeon; Fernández, Facundo M.; Biochemistry and Molecular Biology, School of MedicineNo effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and triple mutant mouse models (n = 4) of high-grade serous ovarian cancer (HGSOC). Lipids belonging to a total of 15 different classes were annotated and their abundance changes were compared to those in healthy mouse reproductive tissue (n = 4), mapping onto major lipid pathways involved in OC progression. From intermediate-stage OC to advanced HGSC, we provide direct visualization of lipid distributions and their biological links to inflammatory response, cellular stress, cell proliferation, and other processes. We also show the ability to distinguish tumors at different stages from healthy tissues via a number of highly specific lipid biomarkers, providing targets for future panels that could be useful in diagnosis.