Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways
Mammalian sperm must undergo capacitation to become fertilization-competent. While working on mice, we recently developed a new methodology for treating sperm in vitro, which results in higher rates of fertilization and embryo development after in vitro fertilization. Sperm incubated in media devoid...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1234221/full |
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| author | Ana Romarowski Ana Romarowski Jasna Fejzo Saman Nayyab David Martin-Hidalgo Maria G. Gervasi Melanie Balbach Sara Violante Ana M. Salicioni Justin Cross Lonny R. Levin Jochen Buck Pablo E. Visconti |
| author_facet | Ana Romarowski Ana Romarowski Jasna Fejzo Saman Nayyab David Martin-Hidalgo Maria G. Gervasi Melanie Balbach Sara Violante Ana M. Salicioni Justin Cross Lonny R. Levin Jochen Buck Pablo E. Visconti |
| author_sort | Ana Romarowski |
| collection | DOAJ |
| description | Mammalian sperm must undergo capacitation to become fertilization-competent. While working on mice, we recently developed a new methodology for treating sperm in vitro, which results in higher rates of fertilization and embryo development after in vitro fertilization. Sperm incubated in media devoid of nutrients lose motility, although they remain viable. Upon re-adding energy substrates, sperm resume motility and become capacitated with improved functionality. Here, we explore how sperm energy restriction and recovery (SER) treatment affects sperm metabolism and capacitation-associated signaling. Using extracellular flux analysis and metabolite profiling and tracing via nuclear magnetic resonance (NMR) and mass spectrometry (MS), we found that the levels of many metabolites were altered during the starvation phase of SER. Of particular interest, two metabolites, AMP and L-carnitine, were significantly increased in energy-restricted sperm. Upon re-addition of glucose and initiation of capacitation, most metabolite levels recovered and closely mimic the levels observed in capacitating sperm that have not undergone starvation. In both control and SER-treated sperm, incubation under capacitating conditions upregulated glycolysis and oxidative phosphorylation. However, ATP levels were diminished, presumably reflecting the increased energy consumption during capacitation. Flux data following the fate of 13C glucose indicate that, similar to other cells with high glucose consumption rates, pyruvate is converted into 13C-lactate and, with lower efficiency, into 13C-acetate, which are then released into the incubation media. Furthermore, our metabolic flux data show that exogenously supplied glucose is converted into citrate, providing evidence that in sperm cells, as in somatic cells, glycolytic products can be converted into Krebs cycle metabolites. |
| first_indexed | 2024-03-12T14:36:13Z |
| format | Article |
| id | doaj.art-6ffc929c917e44778766d6d8e9c7d9a5 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-12T14:36:13Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-6ffc929c917e44778766d6d8e9c7d9a52023-08-17T04:35:56ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-08-011110.3389/fcell.2023.12342211234221Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathwaysAna Romarowski0Ana Romarowski1Jasna Fejzo2Saman Nayyab3David Martin-Hidalgo4Maria G. Gervasi5Melanie Balbach6Sara Violante7Ana M. Salicioni8Justin Cross9Lonny R. Levin10Jochen Buck11Pablo E. Visconti12Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, United StatesInstituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (IBYME-CONICET), Buenos Aires, ArgentinaInstitute for Applied Life Sciences, University of Massachusetts, Amherst, MA, United StatesDepartment of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, United StatesHospital San Pedro de Alcántara, Cáceres, SpainDepartment of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, United StatesDepartment of Pharmacology, Weill Cornell Medicine, New York, NY, United StatesMemorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, United StatesMemorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Pharmacology, Weill Cornell Medicine, New York, NY, United StatesDepartment of Pharmacology, Weill Cornell Medicine, New York, NY, United StatesDepartment of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, United StatesMammalian sperm must undergo capacitation to become fertilization-competent. While working on mice, we recently developed a new methodology for treating sperm in vitro, which results in higher rates of fertilization and embryo development after in vitro fertilization. Sperm incubated in media devoid of nutrients lose motility, although they remain viable. Upon re-adding energy substrates, sperm resume motility and become capacitated with improved functionality. Here, we explore how sperm energy restriction and recovery (SER) treatment affects sperm metabolism and capacitation-associated signaling. Using extracellular flux analysis and metabolite profiling and tracing via nuclear magnetic resonance (NMR) and mass spectrometry (MS), we found that the levels of many metabolites were altered during the starvation phase of SER. Of particular interest, two metabolites, AMP and L-carnitine, were significantly increased in energy-restricted sperm. Upon re-addition of glucose and initiation of capacitation, most metabolite levels recovered and closely mimic the levels observed in capacitating sperm that have not undergone starvation. In both control and SER-treated sperm, incubation under capacitating conditions upregulated glycolysis and oxidative phosphorylation. However, ATP levels were diminished, presumably reflecting the increased energy consumption during capacitation. Flux data following the fate of 13C glucose indicate that, similar to other cells with high glucose consumption rates, pyruvate is converted into 13C-lactate and, with lower efficiency, into 13C-acetate, which are then released into the incubation media. Furthermore, our metabolic flux data show that exogenously supplied glucose is converted into citrate, providing evidence that in sperm cells, as in somatic cells, glycolytic products can be converted into Krebs cycle metabolites.https://www.frontiersin.org/articles/10.3389/fcell.2023.1234221/fullspermassisted reproductive technologiesmetabolismAMPATPcitrate |
| spellingShingle | Ana Romarowski Ana Romarowski Jasna Fejzo Saman Nayyab David Martin-Hidalgo Maria G. Gervasi Melanie Balbach Sara Violante Ana M. Salicioni Justin Cross Lonny R. Levin Jochen Buck Pablo E. Visconti Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways Frontiers in Cell and Developmental Biology sperm assisted reproductive technologies metabolism AMP ATP citrate |
| title | Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways |
| title_full | Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways |
| title_fullStr | Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways |
| title_full_unstemmed | Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways |
| title_short | Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways |
| title_sort | mouse sperm energy restriction and recovery ser revealed novel metabolic pathways |
| topic | sperm assisted reproductive technologies metabolism AMP ATP citrate |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1234221/full |
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