Mechanisms of epigenetic remodelling during preimplantation development

2016 ◽  
Vol 28 (2) ◽  
pp. 25 ◽  
Author(s):  
Pablo Juan Ross ◽  
Sebastian Canovas
Keyword(s):  
Information Needs ◽  
Reproductive Tract ◽  
Environmental Changes ◽  
Primordial Germ Cells ◽  
Early Embryo ◽  
Female Reproductive Tract ◽  
Preimplantation Embryos ◽  
Epigenetic Information ◽  
Health And Disease

Epigenetics involves mechanisms independent of modifications in the DNA sequence that result in changes in gene expression and are maintained through cell divisions. Because all cells in the organism contain the same genetic blueprint, epigenetics allows for cells to assume different phenotypes and maintain them upon cell replication. As such, during the life cycle, there are moments in which the epigenetic information needs to be reset for the initiation of a new organism. In mammals, the resetting of epigenetic marks occurs at two different moments, which both happen to be during gestation, and include primordial germ cells (PGCs) and early preimplantation embryos. Because epigenetic information is reversible and sensitive to environmental changes, it is probably no coincidence that both these extensive periods of epigenetic remodelling happen in the female reproductive tract, under a finely controlled maternal environment. It is becoming evident that perturbations during the extensive epigenetic remodelling in PGCs and embryos can lead to permanent and inheritable changes to the epigenome that can result in long-term changes to the offspring derived from them, as indicated by the Developmental Origins of Health and Disease (DOHaD) hypothesis and recent demonstration of inter- and trans-generational epigenetic alterations. In this context, an understanding of the mechanisms of epigenetic remodelling during early embryo development is important to assess the potential for gametic epigenetic mutations to contribute to the offspring and for new epimutations to be established during embryo manipulations that could affect a large number of cells in the offspring. It is of particular interest to understand whether and how epigenetic information can be passed on from the gametes to the embryo or offspring, and whether abnormalities in this process could lead to transgenerationally inheritable phenotypes. The aim of this review is to highlight recent progress made in understanding the nature and mechanisms of epigenetic remodelling that ensue after fertilisation.

scholarly journals Proteomics and metabolomics in cow fertility: a systematic review

Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. 639-658
Author(s):  
Nicolas Aranciaga ◽  
James D Morton ◽  
Debra K Berg ◽  
Jessica L Gathercole
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Large Scale ◽  
Reproductive Tract ◽  
Early Embryo ◽  
Female Reproductive Tract ◽  
Full Potential ◽  
Technical Standards ◽  
The Impact

Cow subfertility is a multi-factorial problem in many countries which is only starting to be unravelled. Molecular biology can provide a substantial source of insight into its causes and potential solutions, particularly through large scale, untargeted omics approaches. In this systematic review, we set out to compile, assess and integrate the latest proteomic and metabolomic research on cow reproduction, specifically that on the female reproductive tract and early embryo. We herein report a general improvement in technical standards throughout the temporal span examined; however, significant methodological limitations are also identified. We propose easily actionable avenues for ameliorating these shortcomings and enhancing the reach of this field. Text mining and pathway analysis corroborate the relevance of proteins and metabolites related to the triad oxidative stress-inflammation-disease on reproductive function. We envisage a breakthrough in cattle reproductive molecular research within the next few years as in vivo sample techniques are improved, omics analysis equipment becomes more affordable and widespread, and software tools for single- and multi-omics data processing are further developed. Additional investigation of the impact of local oxidative stress and inflammation on fertility, both at the local and systemic levels, is key towards realising the full potential of this field.

scholarly journals Which Low-Abundance Proteins are Present in the Human Milieu of Gamete/Embryo Maternal Interaction?

2019 ◽  
Vol 20 (21) ◽  
pp. 5305 ◽  
Author(s):  
Canha-Gouveia ◽  
Paradela ◽  
Ramos-Fernández ◽  
Prieto-Sánchez ◽  
Sánchez-Ferrer ◽  
...  
Keyword(s):  
Embryo Development ◽  
Reproductive Tract ◽  
Culture Media ◽  
Adult Life ◽  
Early Embryo ◽  
Female Reproductive Tract ◽  
High Throughput Analysis ◽  
Maternal Interaction ◽  
Oviductal Fluid ◽  
Abundance Proteins

The improvement of the embryo culture media is of high relevance due to its influence on successful implantation rates, pregnancy, neonatal outcomes, and potential effects in adult life. The ideal conditions for embryo development are those naturally occurring in the female reproductive tract, i.e., the oviductal and uterine fluids. To shed light on the differences between chemical and natural media, we performed the first comparative study of the low abundance proteins in plasma, uterine, and oviductal fluid collected, simultaneously, from healthy and fertile women that underwent a salpingectomy. The rationale for this design derives from the fact that high-abundant proteins in these fluids are usually those coming from blood serum and frequently mask the detection of low abundant proteins with a potentially significant role in specific processes related to the embryo–maternal interaction. The proteomic analysis by 1D-nano LC ESI-MSMS detected several proteins in higher amounts in oviductal fluid when compared to uterine and plasma samples (RL3, GSTA1, EZRI, DPYSL3, GARS, HSP90A). Such oviductal fluid proteins could be a target to improve fertilization rates and early embryo development if used in the culture media. In conclusion, this study presents a high-throughput analysis of female reproductive tract fluids and contributes to the knowledge of oviductal and uterine secretome.

scholarly journals Seminal Plasma Triggers the Differential Expression of the Glucocorticoid Receptor (NR3C1/GR) in the Rabbit Reproductive Tract

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2158
Author(s):  
Mateo Ruiz-Conca ◽  
Jaume Gardela ◽  
Amaia Jauregi-Miguel ◽  
Cristina A. Martinez ◽  
Heriberto Rodríguez-Martinez ◽  
...  
Keyword(s):  
Differential Expression ◽  
Seminal Plasma ◽  
Time Course ◽  
Reproductive Tract ◽  
Receptor Gene ◽  
Early Embryo ◽  
Female Reproductive Tract ◽  
Relevant Role ◽  
Morula Stage ◽  
Embryo Transport

Rabbits are interesting as research animal models for reproduction, due to their condition of species of induced ovulation, with the release of endogenous gonadotropin-releasing hormone (GnRH) due to coitus. Glucocorticoid (GC) signaling, crucial for physiological homeostasis, is mediated through a yet unclear mechanism, by the GC receptor (NR3C1/GR). After mating, the female reproductive tract undergoes dynamic modifications, triggered by gene transcription, a pre-amble for fertilization and pregnancy. This study tested the hypothesis that when ovulation is induced, the expression of NR3C1 is influenced by sperm-free seminal plasma (SP), similarly to after mating (whole semen), along the different segments of the internal reproductive tract of female rabbits. Semen (mating) was compared to vaginal infusion of sperm-free SP (Experiment 1), and changes over time were also evaluated, i.e., 10, 24, 36, 68, and 72 h post-mating, corresponding to specific stages, i.e., ovulation, fertilization, and the interval of early embryo development up to the morula stage (Experiment 2). All does were treated with GnRH to induce ovulation. Samples were retrieved from seven segments of the reproductive tract (from the cervix to infundibulum), at 20 h post-mating or sperm-free SP infusion (Experiment 1) or at 10, 24, 36, 68, and 72 h post-mating (Experiment 2). Gene expression of NR3C1 was analyzed by qPCR. Results showed an increase in NR3C1 expression in the infundibulum compared to the other anatomical regions in the absence of spermatozoa when sperm-free SP infusion was performed (Experiment 1). Moreover, during the embryo transport through the oviduct, the distal isthmus was time-course upregulated, especially at 72 h, when morulae are retained in this anatomical region, while it was downregulated in the distal uterus at 68 h (Experiment 2). The overall results suggest that NR3C1, the GC receptor gene, assessed in the reproductive tract of does for the first time, shows differential expression changes during the interval of oviductal and uterine embryo transport that may imply a relevant role of the GC action, not only close to the site of ovulation and fertilization, but also in the endometrium.

Female reproductive tract fluids: composition, mechanism of formation and potential role in the developmental origins of health and disease

2008 ◽  
Vol 20 (1) ◽  
pp. 1 ◽  
Author(s):  
Henry J. Leese ◽  
Sasha A. Hugentobler ◽  
Susan M. Gray ◽  
Dermot G. Morris ◽  
Roger G. Sturmey ◽  
...  
Keyword(s):  
Potential Role ◽  
Reproductive Tract ◽  
Maternal Diet ◽  
Female Reproductive Tract ◽  
Developmental Origins ◽  
Mammalian Embryo ◽  
Healthy Pregnancy ◽  
Early Embryos ◽  
Health And Disease ◽  
Uptake Of Nutrients

The oviduct and uterus provide the environments for the earliest stages of mammalian embryo development. However, little is known about the mechanisms that underlie the formation of oviduct and uterine fluids, or the extent to which the supply of nutrients via these reproductive tract tissues matches the nutrient requirements of early embryos. After reviewing our limited knowledge of these phenomena, a new experimental paradigm is proposed in which the epithelia lining the endosalpinx and endometrium are seen as the final components in a supply line that links maternal diet at one end and embryo uptake of nutrients at the other. When considered in this way, the oviduct and uterine epithelia become, for a few days, potentially the most critical maternal tissues in the establishment of a healthy pregnancy. In fulfilling this ‘gatekeeper’ role, female reproductive tract fluids have a key role in the ‘developmental origins of health and disease’ concept.

scholarly journals Measles-based Zika vaccine induces long-term immunity and requires NS1 antibodies to protect the female reproductive tract.

2020 ◽  
Author(s):  
Matthias Schnell ◽  
Drishya Kurup ◽  
Christoph Wirblich
Keyword(s):  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Viral Clearance ◽  
Measles Vaccine ◽  
Fetal Protection ◽  
Cell Responses ◽  
Asian Strain ◽  
African Strain ◽  
The Brain

Abstract Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2, protected mice from the non-lethal Zika Asian strain (PRVABC59) and the lethal African strain (MR766) challenge. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. We then tested a combination of two MV-based vaccines, the MV-E2 and a vaccine expressing NS1 (MV-NS1[2]), and we observed durable plasma cell responses, complete clearance of ZIKV from the female reproductive tract, and complete fetal protection in the lethal African challenge model. Our findings suggest that NS1 antibodies are required to enhance the protection achieved by ZIKV-E antibodies in the female reproductive tract.

scholarly journals Patient-derived endometrial organoids from MRKH patients: Insight in disease causing pathways

2021 ◽  
Author(s):  
Sara Y. Brucker ◽  
Thomas Hentrich ◽  
Julia M. Schulze-Hentrich ◽  
Martin Pietzsch ◽  
Noel Wajngarten ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Ovarian Function ◽  
Female Reproductive Tract ◽  
Mrkh Syndrome ◽  
Powerful Research Tool ◽  
Healthy Control ◽  
Organoid Cultures ◽  
Holding Back

The uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. The Mayer-Rokitansky-Kuester-Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focusses on DNA-sequencing efforts and, so far, failed to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully hormone responsive. Transcriptome analyses, however, identified an array of dysregulated genes that point at potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.

scholarly journals The Central Role of Cadherins in Gonad Development, Reproduction and Fertility

2020 ◽  
Author(s):  
Rafał P. Piprek ◽  
Malgorzata Kloc ◽  
Paulina Mizia ◽  
Jacek Z. KUBIAK
Keyword(s):  
Germ Cells ◽  
Reproductive Tract ◽  
Primordial Germ Cells ◽  
Somatic Cells ◽  
Gonad Development ◽  
Female Reproductive Tract ◽  
Future Research ◽  
Corpora Lutea ◽  
Germline Development

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, the E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells, (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, the N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood-testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes, and facilitate the capacitation of sperm in the female reproductive tract, and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins, however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and suggest the topics for future research.

scholarly journals Nutritional adversity, sex and reproduction: 30 years of DOHaD and what have we learned?

2019 ◽  
Vol 242 (1) ◽  
pp. T51-T68 ◽  
Author(s):  
Patrycja A Jazwiec ◽  
Deborah M Sloboda
Keyword(s):  
Germ Cells ◽  
Early Life ◽  
Disease Risk ◽  
Primordial Germ Cells ◽  
Reproductive Function ◽  
Postnatal Life ◽  
Early Life Adversity ◽  
Increased Risk ◽  
Health And Disease

It is well established that early life environmental signals, including nutrition, set the stage for long-term health and disease risk – effects that span multiple generations. This relationship begins early, in the periconceptional period and extends into embryonic, fetal and early infant phases of life. Now known as the Developmental Origins of Health and Disease (DOHaD), this concept describes the adaptations that a developing organism makes in response to early life cues, resulting in adjustments in homeostatic systems that may prove maladaptive in postnatal life, leading to an increased risk of chronic disease and/or the inheritance of risk factors across generations. Reproductive maturation and function is similarly influenced by early life events. This should not be surprising, since primordial germ cells are established early in life and thus vulnerable to early life adversity. A multitude of ‘modifying’ cues inducing developmental adaptations have been identified that result in changes in reproductive development and impairments in reproductive function. Many types of nutritional challenges including caloric restriction, macronutrient excess and micronutrient insufficiencies have been shown to induce early life adaptations that produce long-term reproductive dysfunction. Many pathways have been suggested to underpin these associations, including epigenetic reprogramming of germ cells. While the mechanisms still remain to be fully investigated, it is clear that a lifecourse approach to understanding lifetime reproductive function is necessary. Furthermore, investigations of the impacts of early life adversity must be extended to include the paternal environment, especially in epidemiological and clinical studies of offspring reproductive function.

Sign in / Sign up

Export Citation Format

Share Document