Excess cholesterol induces mouse egg activation and may cause female infertility
The HDL receptor scavenger receptor, class B type I (SR-BI) controls the structure and fate of plasma HDL. Female SR-BI KO mice are infertile, apparently because of their abnormal cholesterol-enriched HDL particles. We examined the growth and meiotic progression of SR-BI KO oocytes and found that th...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2015
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| Online Access: | http://hdl.handle.net/1721.1/96953 https://orcid.org/0000-0003-2585-0610 https://orcid.org/0000-0001-9920-3411 https://orcid.org/0000-0003-4541-5181 https://orcid.org/0000-0001-9905-5316 |
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| author | Yesilaltay, Ayce Dokshin, Gregoriy A. Busso, Dolores Wang, Li Galiani, Dalia Vasile, Eliza Quilaqueo, Linda Orellana, Juan Andrés Shalgi, Ruth Dekel, Nava Albertini, David F. Rigotti, Attilio Krieger, Monty Walzer, Dalia F. Page, David C Chavarria, Tony E |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Yesilaltay, Ayce Dokshin, Gregoriy A. Busso, Dolores Wang, Li Galiani, Dalia Vasile, Eliza Quilaqueo, Linda Orellana, Juan Andrés Shalgi, Ruth Dekel, Nava Albertini, David F. Rigotti, Attilio Krieger, Monty Walzer, Dalia F. Page, David C Chavarria, Tony E |
| author_sort | Yesilaltay, Ayce |
| collection | MIT |
| description | The HDL receptor scavenger receptor, class B type I (SR-BI) controls the structure and fate of plasma HDL. Female SR-BI KO mice are infertile, apparently because of their abnormal cholesterol-enriched HDL particles. We examined the growth and meiotic progression of SR-BI KO oocytes and found that they underwent normal germinal vesicle breakdown; however, SR-BI KO eggs, which had accumulated excess cholesterol in vivo, spontaneously activated, and they escaped metaphase II (MII) arrest and progressed to pronuclear, MIII, and anaphase/telophase III stages. Eggs from fertile WT mice were activated when loaded in vitro with excess cholesterol by a cholesterol/methyl-β-cyclodextrin complex, phenocopying SR-BI KO oocytes. In vitro cholesterol loading of eggs induced reduction in maturation promoting factor and MAPK activities, elevation of intracellular calcium, extrusion of a second polar body, and progression to meiotic stages beyond MII. These results suggest that the infertility of SR-BI KO females is caused, at least in part, by excess cholesterol in eggs inducing premature activation and that cholesterol can activate WT mouse eggs to escape from MII arrest. Analysis of SR-BI KO female infertility raises the possibility that abnormalities in cholesterol metabolism might underlie some cases of human female infertility of unknown etiology. |
| first_indexed | 2024-09-23T12:33:59Z |
| format | Article |
| id | mit-1721.1/96953 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:33:59Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/969532022-09-28T08:38:38Z Excess cholesterol induces mouse egg activation and may cause female infertility Yesilaltay, Ayce Dokshin, Gregoriy A. Busso, Dolores Wang, Li Galiani, Dalia Vasile, Eliza Quilaqueo, Linda Orellana, Juan Andrés Shalgi, Ruth Dekel, Nava Albertini, David F. Rigotti, Attilio Krieger, Monty Walzer, Dalia F. Page, David C Chavarria, Tony E Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Koch Institute for Integrative Cancer Research at MIT Yesilaltay, Ayce Dokshin, Gregoriy A. Wang, Li Chavarria, Tony E. Vasile, Eliza Walzer, Dalia F. Page, David C. Krieger, Monty The HDL receptor scavenger receptor, class B type I (SR-BI) controls the structure and fate of plasma HDL. Female SR-BI KO mice are infertile, apparently because of their abnormal cholesterol-enriched HDL particles. We examined the growth and meiotic progression of SR-BI KO oocytes and found that they underwent normal germinal vesicle breakdown; however, SR-BI KO eggs, which had accumulated excess cholesterol in vivo, spontaneously activated, and they escaped metaphase II (MII) arrest and progressed to pronuclear, MIII, and anaphase/telophase III stages. Eggs from fertile WT mice were activated when loaded in vitro with excess cholesterol by a cholesterol/methyl-β-cyclodextrin complex, phenocopying SR-BI KO oocytes. In vitro cholesterol loading of eggs induced reduction in maturation promoting factor and MAPK activities, elevation of intracellular calcium, extrusion of a second polar body, and progression to meiotic stages beyond MII. These results suggest that the infertility of SR-BI KO females is caused, at least in part, by excess cholesterol in eggs inducing premature activation and that cholesterol can activate WT mouse eggs to escape from MII arrest. Analysis of SR-BI KO female infertility raises the possibility that abnormalities in cholesterol metabolism might underlie some cases of human female infertility of unknown etiology. National Institutes of Health (U.S.) National Institutes of Health (U.S.) (Pre-doctoral Training Grant T32GM007287) Massachusetts Institute of Technology (International Science and Technology Initiatives Chile Cooperative Grant) 2015-05-11T14:19:30Z 2015-05-11T14:19:30Z 2014-11 2013-07 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/96953 Yesilaltay, Ayce, Gregoriy A. Dokshin, Dolores Busso, Li Wang, Dalia Galiani, Tony Chavarria, Eliza Vasile, et al. “Excess Cholesterol Induces Mouse Egg Activation and May Cause Female Infertility.” Proceedings of the National Academy of Sciences 111, no. 46 (November 3, 2014): E4972–E4980. https://orcid.org/0000-0003-2585-0610 https://orcid.org/0000-0001-9920-3411 https://orcid.org/0000-0003-4541-5181 https://orcid.org/0000-0001-9905-5316 en_US http://dx.doi.org/10.1073/pnas.1418954111 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Yesilaltay, Ayce Dokshin, Gregoriy A. Busso, Dolores Wang, Li Galiani, Dalia Vasile, Eliza Quilaqueo, Linda Orellana, Juan Andrés Shalgi, Ruth Dekel, Nava Albertini, David F. Rigotti, Attilio Krieger, Monty Walzer, Dalia F. Page, David C Chavarria, Tony E Excess cholesterol induces mouse egg activation and may cause female infertility |
| title | Excess cholesterol induces mouse egg activation and may cause female infertility |
| title_full | Excess cholesterol induces mouse egg activation and may cause female infertility |
| title_fullStr | Excess cholesterol induces mouse egg activation and may cause female infertility |
| title_full_unstemmed | Excess cholesterol induces mouse egg activation and may cause female infertility |
| title_short | Excess cholesterol induces mouse egg activation and may cause female infertility |
| title_sort | excess cholesterol induces mouse egg activation and may cause female infertility |
| url | http://hdl.handle.net/1721.1/96953 https://orcid.org/0000-0003-2585-0610 https://orcid.org/0000-0001-9920-3411 https://orcid.org/0000-0003-4541-5181 https://orcid.org/0000-0001-9905-5316 |
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