Embryonic diapause in roe deer: A model to unravel embryo-maternal communication during pre-implantation development in wildlife and livestock species

Weijden, Vera van der; Ulbrich, Susanne E.

doi:10.1016/j.theriogenology.2020.06.042

Cited by 13 publications

(12 citation statements)

References 85 publications

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“…The latter is a common feature of all ungulates preceding implantation. Different from other known species exhibiting diapause, roe deer and nine-banded armadillo embryos continuously increase in size and cell number over the course of diapause (4)(5)(6). In the diapausing roe deer embryo, less than 10% of cells stain positive for the proliferation marker Ki67, and the fraction of Ki67-positive cells is slightly lower in the trophectoderm (TE) than in the inner cell mass (ICM) (7).…”

mentioning

confidence: 98%

Amino acids activate mTORC1 to release roe deer embryos from decelerated proliferation during diapause

Weijden

Bick

Bauersachs

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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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 3 wk. 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.

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mentioning

confidence: 98%

Amino acids activate mTORC1 to release roe deer embryos from decelerated proliferation during diapause

Weijden

Bick

Bauersachs

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…Likewise, polyamine abundance, i.e., less spermine, more spermidine and putrescine, likely increase upon reactivation in the uterine fluid of roe deer (van der Weijden et al, 2019). Other diapause-associated microenvironmental changes include adhesion-and cell cycle-related proteins, further corroborating maternal control over embryo attachment and proliferation (Lefèvre et al, 2011a;Martin et al, 2016;van der Weijden et al, 2019).…”

Section: The Uterine Microenvironmentmentioning

confidence: 74%

“…This more severe phenotype compared to Esrrb KO suggests the involvement of cellular adhesion pathways in establishing the diapause state (Fan et al, 2020). Indeed, several genomic profiling studies comparing diapause and active blastocysts documented altered expression of cellular adhesion genes (Hamatani et al, 2004;Fu et al, 2014;van der Weijden et al, 2019). Adhesion pathways and the cytoskeleton are not merely structural components of the cell, but also affect transcriptional networks, as they are additionally involved in signaling pathways and chromatin regulation (Klages-Mundt et al, 2018;Griffith et al, 2021).…”

Section: Wnt Pathway Activity and The Interplay With Cellular Polarizationmentioning

confidence: 99%

“…Indeed, only about 40% of gene activity is explainable by nascent transcription, although the exact fraction is cell-type dependent (Buccitelli and Selbach, 2020). MicroRNAs (miRNA) are small non-coding RNAs that largely repress gene activity via transcriptional silencing, transcript degradation or translation inhibition (Treiber et al, 2019). MiRNA-mediated gene repression combines sequence specificity with promiscuity (due to short seed sequence and by allowing mismatches), thereby allowing control of multiple target genes at once (O'Brien et al, 2018).…”

Section: Post-transcriptional and Post-translational Gene Regulation In Diapausementioning

confidence: 99%

“…Dissection of downstream pathways can enhance our understanding of how miRNAs regulate diapause. MiRNAs are often in feedback control with cellular pathways and active miRNA levels are regulated either transcriptionally, post-transcriptionally (with selective processing), or via sequestration of mature miRNAs, thus acute functional perturbations are necessary to dissect the regulatory complexity of miRNA activity (Treiber et al, 2019).…”

Section: Post-transcriptional and Post-translational Gene Regulation In Diapausementioning

confidence: 99%

See 2 more Smart Citations

Molecular Regulation of Paused Pluripotency in Early Mammalian Embryos and Stem Cells

Weijden

Bulut-Karslıoğlu

2021

Front. Cell Dev. Biol.

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The energetically costly mammalian investment in gestation and lactation requires plentiful nutritional sources and thus links the environmental conditions to reproductive success. Flexibility in adjusting developmental timing enhances chances of survival in adverse conditions. Over 130 mammalian species can reversibly pause early embryonic development by switching to a near dormant state that can be sustained for months, a phenomenon called embryonic diapause. Lineage-specific cells are retained during diapause, and they proliferate and differentiate upon activation. Studying diapause thus reveals principles of pluripotency and dormancy and is not only relevant for development, but also for regeneration and cancer. In this review, we focus on the molecular regulation of diapause in early mammalian embryos and relate it to maintenance of potency in stem cells in vitro. Diapause is established and maintained by active rewiring of the embryonic metabolome, epigenome, and gene expression in communication with maternal tissues. Herein, we particularly discuss factors required at distinct stages of diapause to induce, maintain, and terminate dormancy.

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Evidence for a male‐biased sex ratio in the offspring of a large herbivore: The role of environmental conditions in the sex ratio variation

Hagen

Ortmann

Elliger³

et al. 2022

Ecology and Evolution

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Numerous studies have examined whether the primary and/or secondary sex ratio in mammals, including humans, deviates from an equilibrium of 1:1. Although effect size in the sex ratio variation is expected to be low, a large sample size allows the identification of even small deviations from parity. In this study, we investigated whether the sex ratio of roe deer (Capreolus capreolus) offspring at birth approaches parity, using a large data set from roe deer offspring tagged in Baden‐Württemberg (Germany, 1972–2019, N = 12,437). In addition, a systematic re‐analysis of available data on the secondary sex ratios of roe deer was conducted to test whether our finding withstood the accumulation of further data. The null hypothesis that the sex ratio of roe deer (prenatal sex ratio and sex ratio at birth) approaches parity was rejected. Moreover, the secondary sex ratio of roe deer offspring deviated from the male‐biased mean for relatively cold or warm weather conditions during autumn and winter. Our study provides strong evidence for a male‐biased sex ratio in a large herbivore and weak evidence for variations in the secondary sex ratio owing to environmental conditions. The pattern is highly relevant in the context of climate change and its impact on the population dynamics of large herbivores.

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Embryonic diapause in roe deer: A model to unravel embryo-maternal communication during pre-implantation development in wildlife and livestock species

Cited by 13 publications

References 85 publications

Amino acids activate mTORC1 to release roe deer embryos from decelerated proliferation during diapause

Amino acids activate mTORC1 to release roe deer embryos from decelerated proliferation during diapause

Molecular Regulation of Paused Pluripotency in Early Mammalian Embryos and Stem Cells

Evidence for a male‐biased sex ratio in the offspring of a large herbivore: The role of environmental conditions in the sex ratio variation

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