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DOI10.1073/pnas.2100500118
Amino acids activate mTORC1 to release roe deer embryos from decelerated proliferation during diapause
Van Der Weijden V.A.; Bick J.T.; Bauersachs S.; Rüegg A.B.; Hildebrandt T.B.; Goeritz F.; Jewgenow K.; Giesbertz P.; Daniel H.; Derisoud E.; Chavatte-Palmer P.; Bruckmaier R.M.; Drews B.; Ulbrich S.E.
发表日期2021
ISSN0027-8424
卷号118期号:35
英文摘要Embryonic diapause in mammals leads to a reversible developmental arrest. While completely halted in many species, European roe deer (Capreolus capreolus) embryos display a continuous deceleration of proliferation. During a 4-mo period, the cell doubling time is 2 to 3wk. During this period, the preimplantation blastocyst reaches a diameter of 4 mm, after which it resumes a fast developmental pace to subsequently implant. The mechanisms regulating this notable deceleration and reacceleration upon developmental resumption are unclear. We propose that amino acids of maternal origin drive the embryonic developmental pace. A pronounced change in the abundance of uterine fluid mTORC1-activating amino acids coincided with an increase in embryonic mTORC1 activity prior to the resumption of development. Concurrently, genes related to the glycolytic and phosphate pentose pathway, the TCA cycle, and one carbon metabolism were up-regulated. Furthermore, the uterine luminal epithelial transcriptome indicated increased estradiol-17β signaling, which likely regulates the endometrial secretions adapting to the embryonic needs. While mTORC1 was predicted to be inactive during diapause, the residual embryonic mTORC2 activity may indicate its involvement in maintaining the low yet continuous proliferation rate during diapause. Collectively, we emphasize the role of nutrient signaling in preimplantation embryo development. We propose selective mTORC1 inhibition via uterine catecholestrogens and let-7 as a mechanism regulating slow stem cell cycle progression. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Embryo development; Embryonic diapause; European roe deer (Capreolus capreolus)
语种英语
scopus关键词amino acid; carbon; catechol estrogen; estradiol; insulin; mammalian target of rapamycin complex 1; RNA; somatomedin; transcriptome; animal experiment; Article; blastocyst; carbon metabolism; cell proliferation; citric acid cycle; controlled study; deceleration; developmental stage; diapause; embryo; embryo development; glycolysis; nonhuman; oxidative phosphorylation; pentose phosphate cycle; RNA translation; roe deer; upregulation; uterus fluid
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/238410
作者单位Animal Physiology, Institute of Agricultural Sciences, Eidgenössische Technische Hochschule Zurich, Zurich, 8092, Switzerland; Functional Genomics Group, Institute of Veterinary Anatomy, University of Zurich, Lindau, CH-8315, Switzerland; Reproduction Management, Leibniz Institute for Zoo and Wildlife Research, Berlin, 10315, Germany; Reproduction Biology, Leibniz Institute for Zoo and Wildlife Research, Berlin, 10315, Germany; Nutritional Physiology, Technische Universität München, Freising, 85354, Germany; Université Paris-Saclay, Université Versailles-Saint Quentin, INRAE, Biology of Reproduction, Environment, Epigenetic and Development (BREED), Jouy-en-Josas, 78350, France; Ecole Nationale Vétérinaire d'Alfort, Biology of Reproduction Environment Epigenetic and Development (BREED), Maisons-Alfort, 94700, France; Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, 3001, Switzerland
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Van Der Weijden V.A.,Bick J.T.,Bauersachs S.,et al. Amino acids activate mTORC1 to release roe deer embryos from decelerated proliferation during diapause[J],2021,118(35).
APA Van Der Weijden V.A..,Bick J.T..,Bauersachs S..,Rüegg A.B..,Hildebrandt T.B..,...&Ulbrich S.E..(2021).Amino acids activate mTORC1 to release roe deer embryos from decelerated proliferation during diapause.Proceedings of the National Academy of Sciences of the United States of America,118(35).
MLA Van Der Weijden V.A.,et al."Amino acids activate mTORC1 to release roe deer embryos from decelerated proliferation during diapause".Proceedings of the National Academy of Sciences of the United States of America 118.35(2021).
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