The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Susan S. Suarez - One of the best experts on this subject based on the ideXlab platform.
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Rethinking the relationship between Hyperactivation and chemotaxis in mammalian sperm
2016Co-Authors: Haixin Chang, Susan S. SuarezAbstract:Hyperactivation, a motility pattern of mammalian sperm in the oviduct, is essential to fertilization. Hyperactivation helps sperm to swim effectively through oviductal mucus, to escape from the sperm reservoir, and to penetrate the cumulus matrix and zona pellucida of the oocyte. There is some evidence that mammalian sperm can undergo chemotaxis; however, the relationship of chemotaxis to Hyperactivation is unknown. Ca2+ signaling is involved in Hyperactivation and implicated in chemotaxis as well. In vivo, sperm hyperactivate in the lower oviduct, far from the cumulus-oocyte complex and possibly beyond the influence of chemotactic gradients emanating from the oocyte or cumulus. Thus, sperm are likely to be hyper-activated before sensing chemotactic gradients. Chemotactic signals might modulate Hyperactivation to direct sperm toward oocytes as they reach a region of influence. Ca2+-directed modulation of Hyperactivation is a potential mechanism of this process. calcium, chemotaxis, fallopian tubes, Hyperactivation, oviduct, sperm, sperm motility and transport, spermatozoa, uterine tub
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ejaculated mouse sperm enter cumulus oocyte complexes more efficiently in vitro than epididymal sperm
PLOS ONE, 2015Co-Authors: Peihsuan Hung, Susan S. SuarezAbstract:The mouse is an established and popular animal model for studying reproductive biology. Epididymal mouse sperm, which lack exposure to secretions of male accessory glands and do not precisely represent ejaculated sperm for the study of sperm functions, have been almost exclusively used in studies. We compared ejaculated and epididymal sperm in an in vitro fertilization setting to examine whether ejaculated sperm enter cumulus-oocyte complexes more efficiently. In order to prepare sperm for fertilization, they were incubated under capacitating conditions. At the outset of incubation, ejaculated sperm stuck to the glass surfaces of slides and the incidences of sticking decreased with time; whereas, very few epididymal sperm stuck to glass at any time point, indicating differences in surface charge. At the end of the capacitating incubation, when sperm were added to cumulus-oocyte complexes, the form of flagellar movement differed dramatically; specifically, ejaculated sperm predominantly exhibited increased bending on one side of the flagellum (a process termed pro-hook Hyperactivation), while epididymal sperm equally exhibited increased bending on one or the other side of the flagellum (pro-hook or anti-hook Hyperactivation). This indicates that accessory sex gland secretions might have modified Ca2+ signaling activities in sperm, because the two forms of Hyperactivation are reported to be triggered by different Ca2+ signaling patterns. Lastly, over time, more ejaculated than epididymal sperm entered the cumulus oocyte complexes. We concluded that modification of sperm by male accessory gland secretions affects the behavior of ejaculated sperm, possibly providing them with an advantage over epididymal sperm for reaching the eggs in vivo.
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rethinking the relationship between Hyperactivation and chemotaxis in mammalian sperm
Biology of Reproduction, 2010Co-Authors: Haixin Chang, Susan S. SuarezAbstract:Hyperactivation, a motility pattern of mammalian sperm in the oviduct, is essential to fertilization. Hyperactivation helps sperm to swim effectively through oviductal mucus, to escape from the sperm reservoir, and to penetrate the cumulus matrix and zona pellucida of the oocyte. There is some evidence that mammalian sperm can undergo chemotaxis; however, the relationship of chemotaxis to Hyperactivation is unknown. Ca2+ signaling is involved in Hyperactivation and implicated in chemotaxis as well. In vivo, sperm hyperactivate in the lower oviduct, far from the cumulus-oocyte complex and possibly beyond the influence of chemotactic gradients emanating from the oocyte or cumulus. Thus, sperm are likely to be hyperactivated before sensing chemotactic gradients. Chemotactic signals might modulate Hyperactivation to direct sperm toward oocytes as they reach a region of influence. Ca2+-directed modulation of Hyperactivation is a potential mechanism of this process.
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control of Hyperactivation in sperm
Human Reproduction Update, 2008Co-Authors: Susan S. SuarezAbstract:BACKGROUND: Sperm Hyperactivation is critical to fertilization, because it is required for penetration of the zona pellucida. Hyperactivation may also facilitate release of sperm from the oviductal storage reservoir and may propel sperm through mucus in the oviductal lumen and the matrix of the cumulus oophorus. Hyperactivation is characterized by high amplitude, asymmetrical flagellar bending. METHODS: This is a review of the original literature on the mechanisms that regulate Hyperactivation, including physiological factors and signaling pathways. RESULTS: Computer-assisted semen analysis systems can be used to identify hyperactivated sperm by setting minimum thresholds for curvilinear velocity (VSL) and lateral head movement and a maximum threshold for path linearity. Hyperactivation is triggered by a rise in flagellar Ca(2+) resulting from influx primarily through plasma membrane CatSper channels and possibly also by release of Ca(2+) from a store in the redundant nuclear envelope. It requires increased pH and ATP production. The physiological signals that trigger the rise in Ca(2+) remain elusive, but there is evidence that the increased Ca(2+) acts through a calmodulin/calmodulin kinase pathway. Hyperactivation is considered part of the capacitation process; however, the regulatory pathway that triggers Hyperactivation can operate independently from that which prepares sperm to undergo the acrosome reaction. Hyperactivation may be modulated by chemotactic signals to turn sperm toward the oocyte. CONCLUSIONS: Little is known about exactly what triggers Hyperactivation in human sperm. This information could enable clinicians to develop reliable fertility assays to assess normal Hyperactivation in human sperm samples.
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Hyperactivation of stallion sperm is required for successful in vitro fertilization of equine oocytes
Biology of Reproduction, 2008Co-Authors: L A Mcpartlin, Susan S. Suarez, Catherine A Czaya, K Hinrichs, Sylvia J BedfordguausAbstract:Capacitation is a complex and not well-understood process that encompasses all the molecular changes sperm must undergo to successfully fertilize an oocyte. In vitro fertilization has remained elusive in the horse, as evidenced by low in vitro fertilization (IVF) rates (0%-33%); moreover, only two foals have ever been produced using IVF. Incubation of stallion sperm in modified Whittens supplemented with bovine serum albumin and sodium bicarbonate yielded significant rates of time-dependent protein tyrosine phosphorylation and induced acrosomal exocytosis, consistent with capacitation. The objective of this study was to characterize stallion sperm Hyperactivation and to test whether Hyperactivation of capacitated sperm supported equine IVF. Treatment of sperm with procaine, an anesthetic shown to induce Hyperactivation in other mammalian species, resulted in the decrease of three motility variables indicative of Hyperactivation: straight line velocity (P = 0.029), straightness (P = 0.001), and linearity (P = 0.002). We demonstrated that procaine-induced Hyperactivation was not regulated by changes in protein tyrosine phosphorylation and that it did not induce acrosomal exocytosis in capacitated sperm compared with calcium ionophore (P > 0.05), similar to findings in the bovine. Most notably, by coupling our capacitating conditions with the induction of Hyperactivation using procaine, we have achieved the novel result of substantial and reproducible percentages of fertilized mare oocytes (60.7%) in our IVF experiments. Conversely, sperm incubated in capacitating conditions but not treated with procaine did not fertilize (0%). These results support the hypothesis that capacitation and Hyperactivation are required for successful IVF in the equine.
Hiroji Iwata - One of the best experts on this subject based on the ideXlab platform.
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alpelisib alp with fulvestrant ful in patients pts with pik3ca mutated hormone receptor positive hr human epidermal growth factor receptor 2 negative her2 advanced breast cancer abc primary or secondary resistance to prior endocrine therapy et in the
Journal of Clinical Oncology, 2019Co-Authors: Dejan Juric, Christelle Levy, Ignacio Delgado J Mingorance, Frederic Forget, Fabrice Andre, Pierfranco Conte, Norikazu Masuda, Mario Campone, Sibylle Loibl, Hiroji IwataAbstract:1038Background: A contributor to ETR, phosphatidylinositol 3-kinase (PI3K) pathway Hyperactivation can result from mutations to PIK3CA; ~40% of pts with HR+, HER2– ABC exhibit tumors with this muta...
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patient reported outcomes pros in patients pts with pik3ca mutated hormone receptor positive hr human epidermal growth factor receptor 2 negative her2 advanced breast cancer abc from solar 1
Journal of Clinical Oncology, 2019Co-Authors: Ingrid A Mayer, Hiroji Iwata, Fabrice Andre, Pierfranco Conte, Sibylle Loibl, Hope S Rugo, Tamar Safra, Yeon Hee Park, Petr Krivorotko, Eva CiruelosAbstract:1039Background: Approximately 40% of pts with HR+, HER2– ABC have tumors with a PIK3CA mutation, resulting in phosphatidylinositol 3-kinase (PI3K) pathway Hyperactivation. Use of the oral α-specifi...
Eva Ciruelos - One of the best experts on this subject based on the ideXlab platform.
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patient reported outcomes pros in patients pts with pik3ca mutated hormone receptor positive hr human epidermal growth factor receptor 2 negative her2 advanced breast cancer abc from solar 1
Journal of Clinical Oncology, 2019Co-Authors: Ingrid A Mayer, Hiroji Iwata, Fabrice Andre, Pierfranco Conte, Sibylle Loibl, Hope S Rugo, Tamar Safra, Yeon Hee Park, Petr Krivorotko, Eva CiruelosAbstract:1039Background: Approximately 40% of pts with HR+, HER2– ABC have tumors with a PIK3CA mutation, resulting in phosphatidylinositol 3-kinase (PI3K) pathway Hyperactivation. Use of the oral α-specifi...
Sibylle Loibl - One of the best experts on this subject based on the ideXlab platform.
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alpelisib alp with fulvestrant ful in patients pts with pik3ca mutated hormone receptor positive hr human epidermal growth factor receptor 2 negative her2 advanced breast cancer abc primary or secondary resistance to prior endocrine therapy et in the
Journal of Clinical Oncology, 2019Co-Authors: Dejan Juric, Christelle Levy, Ignacio Delgado J Mingorance, Frederic Forget, Fabrice Andre, Pierfranco Conte, Norikazu Masuda, Mario Campone, Sibylle Loibl, Hiroji IwataAbstract:1038Background: A contributor to ETR, phosphatidylinositol 3-kinase (PI3K) pathway Hyperactivation can result from mutations to PIK3CA; ~40% of pts with HR+, HER2– ABC exhibit tumors with this muta...
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patient reported outcomes pros in patients pts with pik3ca mutated hormone receptor positive hr human epidermal growth factor receptor 2 negative her2 advanced breast cancer abc from solar 1
Journal of Clinical Oncology, 2019Co-Authors: Ingrid A Mayer, Hiroji Iwata, Fabrice Andre, Pierfranco Conte, Sibylle Loibl, Hope S Rugo, Tamar Safra, Yeon Hee Park, Petr Krivorotko, Eva CiruelosAbstract:1039Background: Approximately 40% of pts with HR+, HER2– ABC have tumors with a PIK3CA mutation, resulting in phosphatidylinositol 3-kinase (PI3K) pathway Hyperactivation. Use of the oral α-specifi...
Pierfranco Conte - One of the best experts on this subject based on the ideXlab platform.
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alpelisib alp with fulvestrant ful in patients pts with pik3ca mutated hormone receptor positive hr human epidermal growth factor receptor 2 negative her2 advanced breast cancer abc primary or secondary resistance to prior endocrine therapy et in the
Journal of Clinical Oncology, 2019Co-Authors: Dejan Juric, Christelle Levy, Ignacio Delgado J Mingorance, Frederic Forget, Fabrice Andre, Pierfranco Conte, Norikazu Masuda, Mario Campone, Sibylle Loibl, Hiroji IwataAbstract:1038Background: A contributor to ETR, phosphatidylinositol 3-kinase (PI3K) pathway Hyperactivation can result from mutations to PIK3CA; ~40% of pts with HR+, HER2– ABC exhibit tumors with this muta...
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patient reported outcomes pros in patients pts with pik3ca mutated hormone receptor positive hr human epidermal growth factor receptor 2 negative her2 advanced breast cancer abc from solar 1
Journal of Clinical Oncology, 2019Co-Authors: Ingrid A Mayer, Hiroji Iwata, Fabrice Andre, Pierfranco Conte, Sibylle Loibl, Hope S Rugo, Tamar Safra, Yeon Hee Park, Petr Krivorotko, Eva CiruelosAbstract:1039Background: Approximately 40% of pts with HR+, HER2– ABC have tumors with a PIK3CA mutation, resulting in phosphatidylinositol 3-kinase (PI3K) pathway Hyperactivation. Use of the oral α-specifi...