- Reproductive Physiology in Livestock
- Reproductive Biology and Fertility
- Reproductive System and Pregnancy
- Pluripotent Stem Cells Research
- Renal and related cancers
- Genetic and phenotypic traits in livestock
- Birth, Development, and Health
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Animal Genetics and Reproduction
- Ecology and biodiversity studies
- Wildlife Ecology and Conservation
- Genetics, Aging, and Longevity in Model Organisms
- 14-3-3 protein interactions
- Adipose Tissue and Metabolism
- Genetic Mapping and Diversity in Plants and Animals
- RNA Research and Splicing
- Estrogen and related hormone effects
- Environmental and Sediment Control
- Sperm and Testicular Function
- Nanoparticles: synthesis and applications
- Infant Health and Development
- Infant Nutrition and Health
- Effects and risks of endocrine disrupting chemicals
ETH Zurich
2017-2024
Max Planck Institute for Molecular Genetics
2021-2024
Board of the Swiss Federal Institutes of Technology
2020-2021
Instituto de Ciencias Agrarias
2019
Abstract Mammalian developmental timing is adjustable in vivo by preserving pre-implantation embryos a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development vitro, yet how embryonic dormancy maintained not known. Here we show that diapause are sustained using lipids as primary energy source. In supplementation with metabolite l -carnitine balances lipid consumption, puts deeper and boosts embryo longevity. We identify FOXO1 an essential...
Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved decreasing activity of growth-regulating mTOR signaling pathway. It unknown whether ability conserved in general and humans particular. Here, we show that pathway induces human pluripotent stem cells (hPSCs) blastoids to enter a with limited proliferation, developmental progression, capacity attach endometrial cells. These...
SUMMARY Many mammals can control the timing of gestation and birth by pausing embryonic development at blastocyst stage. It is unknown whether capacity to pause conserved, in general across mammals, more specifically humans. Activity growth regulating mTOR pathway governs developmental mouse ( 1 ). Here we show a stage-specific delay progression human via inhibition. In this context, blastoids pluripotent stem cells naïve naïve-like, but not primed, states be induced enter dormant state,...
Abstract Embryonic diapause in mammals is a temporary developmental delay occurring at the blastocyst stage. In contrast to other diapausing species displaying full arrest, of European roe deer ( Capreolus capreolus ) proliferates continuously and displays considerable morphological changes inner cell mass. We hypothesised that progression also continues during this period. Here we evaluate mRNA abundance marker genes embryos elongation. Our results show rearrangements epiblast correlate...
Dormancy is an essential biological process for the propagation of many life forms through generations and stressful conditions. Early embryos mammals are preservable weeks to months within uterus in a dormant state called diapause, which can be induced vitro mTOR inhibition. Cellular strategies that safeguard original cell identity silent genomic landscape dormancy not known. Here we show protection cis-regulatory elements from silencing key maintaining pluripotency state. We reveal...
The uterine microenvironment during pre-implantation presents a pro-survival milieu and is essential for embryo elongation in ruminants. European roe deer ( Careolus capreolus ) development characterised by 4-month period of reduced development, embryonic diapause, after which the rapidly elongates implants. We investigated fluid proteome label-free liquid chromatography tandem mass spectrometry at four defined stages covering phase developmental pace (early mid-diapause late diapause)...
Significance In mammals, embryo development can halt at the hatched blastocyst stage. Uniquely, proliferation of diapausing embryonic roe deer cells decelerates to a doubling time 2 3 wk over period 4 mo. We highlight nutrient sensing as an important factor regulating developmental pace. The resumption is characterized by increase in uterine fluid mTORC1-activating amino acids, mTORC1 activity, and expression metabolism cell cycle genes. propose selective inhibition via reduced estrogen...
Endocrine disrupting chemicals (EDC) interfere with the natural hormone balance and may induce epigenetic changes through exposure during sensitive periods of development. In this study, effects short-term estradiol-17β (E2) on various tissues pregnant sows (F0) day 10 blastocysts (F1) were assessed. Intergenerational investigated in liver 1-year old female offspring (F1). During gestation, orally exposed to two low doses a high dose E2 (0.05, 10, 1000 µg/kg body weight/day). F0, perturbed...
We recently developed an air-liquid interface long-term culture of differentiated bovine oviductal epithelial cells (ALI-BOEC). This ex vivo oviduct epithelium is capable supporting embryo development in co-culture up to the blastocyst stage without addition medium. However, rates were markedly lower than conventional vitro production procedures. In present study, we assessed target gene expression ALI-BOEC derived embryos test their similarity from culture. screened previously published...
Abstract Background The transcriptional changes around the time of embryonic genome activation in pre-implantation embryos indicate that this process is highly dynamic. In vitro produced porcine blastocysts are known to be less competent than vivo developed blastocysts. To understand conditions compromise developmental competence embryos, it crucial evaluate profile during stages. study, we investigated transcriptome dynamics and 4-cell morulae hatched Results displayed largely similar...
Embryonic diapause in the European roe deer includes a period of five months from August to December which embryonic development is extremely decelerated. Following exit diapause, embryo rapidly elongates and subsequently implants. In diapausing carnivores marsupials, resumption growth regulated by ovarian steroid hormones. deer, role hormones not known date. present study, progesterone (P4), estradiol-17β (E2) total estrogens (Etot) were determined blood plasma endometrium shot course...
Abstract Numerous intrauterine changes take place across species during embryo development. Following fertilization in July/August, the European roe deer (Capreolus capreolus) undergoes diapause until embryonic elongation December/January. Embryonic prior to implantation is a common feature among ungulates. Unlike many other ruminants, does not secrete interferon-tau (IFNτ). This provides unique opportunity unravel IFNτ-independent signaling pathways associated with maternal recognition of...
Abstract The quest to model and modulate embryonic development became a recent cornerstone of stem cell developmental biology. Mammalian timing is adjustable in vivo by preserving preimplantation embryos dormant state called diapause. Inhibition the growth regulator mTOR (mTORi) pauses mouse vitro, yet constraints pause duration are unrecognized. By comparing response extraembryonic cells mTORi-induced pausing, we identified lipid usage as bottleneck pausing. Enhancing fatty acid oxidation...
Progesterone (P4) plays a pivotal role in maintenance of pregnancy many mammalian species. Species-specific P4 metabolites have been shown to function as primary acting progestogen and the receptor binding capacity varies between The European roe deer (Capreolus capreolus) displays 4-5 month period embryonic diapause, which decouples fertilization from implantation. majority two corpora lutea that secrete P4. No changes concentrations observed during pre-implantation embryo development. As...
Embryonic and adult stem cells enable development regeneration. cells, like can enter dormancy as part of their lifecycle. Recent evidence suggests that this cellular transition to requires active rewiring metabolism. The dormancy-induced metabolic switches in embryonic are explored here.
Abstract During early pregnancy, porcine conceptuses (the embryos with associated membranes) secrete estradiol-17β (E2)—their major signal for maternal recognition of pregnancy—and prostaglandin E2 (PGE2). Both hormones induce prominent changes the endometrial transcriptome in vivo. Studies on pathologies have shown that affects gene expression by epigenetic mechanisms related to DNA methylation. Herein, we determined effects and PGE2 alone, a combined + treatment administered into uterine...
Preimplantation bovine blastocyst supernatants exhibit sex-dependent antiviral activity, due to the ruminant pregnancy recognition signal Interferon tau (IFNT). Differing potencies of IFNT variants have been supposed as cause, although evidence remains scarce. Here, we aimed at quantifying production on transcriptional, translational, and biological activity level in blastocysts, elucidate origin differences between male female blastocysts. Day 8 blastocysts were co-cultured with endometrial...
In species displaying embryonic diapause, the developmental pace of embryo is either temporarily and reversibly halted or largely reduced. Only limited knowledge on its regulation inhibition cell proliferation extending pluripotency available. contrast with embryos from other diapausing that halt during roe deer Capreolus capreolus slowly proliferate over a period 4-5 months to reach diameter approximately 4mm before elongation. The present an interesting model for research preimplantation...