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Open AccessEditorial

Molecular and Clinical Advances in Understanding Early Embryo Development

by Lon J. Van Winkle

Cells 2023, 12(8), 1171; https://doi.org/10.3390/cells12081171 - 16 Apr 2023

Viewed by 906

Abstract

The articles in this Special Issue address a wide variety of topics concerning molecular and clinical advances in understanding early embryo development [...] Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

Research

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13 pages, 2044 KiB

Open AccessArticle

Stage-Specific L-Proline Uptake by Amino Acid Transporter Slc6a19/B⁰AT1 Is Required for Optimal Preimplantation Embryo Development in Mice

by Tamara Treleaven, Matthew Zada, Rajini Nagarajah, Charles G. Bailey, John E. J. Rasko, Michael B. Morris and Margot L. Day

Cells 2023, 12(1), 18; https://doi.org/10.3390/cells12010018 - 21 Dec 2022

Cited by 4 | Viewed by 1722

Abstract

L-proline (Pro) has previously been shown to support normal development of mouse embryos. Recently we have shown that Pro improves subsequent embryo development when added to fertilisation medium during in vitro fertilisation of mouse oocytes. The mechanisms by which Pro improves embryo development [...] Read more.

L-proline (Pro) has previously been shown to support normal development of mouse embryos. Recently we have shown that Pro improves subsequent embryo development when added to fertilisation medium during in vitro fertilisation of mouse oocytes. The mechanisms by which Pro improves embryo development are still being elucidated but likely involve signalling pathways that have been observed in Pro-mediated differentiation of mouse embryonic stem cells. In this study, we show that B⁰AT1, a neutral amino acid transporter that accepts Pro, is expressed in mouse preimplantation embryos, along with the accessory protein ACE2. B⁰AT1 knockout (Slc6a19^−/−) mice have decreased fertility, in terms of litter size and preimplantation embryo development in vitro. In embryos from wild-type (WT) mice, excess unlabelled Pro inhibited radiolabelled Pro uptake in oocytes and 4–8-cell stage embryos. Radiolabelled Pro uptake was reduced in 4–8-cell stage embryos, but not in oocytes, from Slc6a19^−/− mice compared to those from WT mice. Other B⁰AT1 substrates, such as alanine and leucine, reduced uptake of Pro in WT but not in B⁰AT1 knockout embryos. Addition of Pro to culture medium improved embryo development. In WT embryos, Pro increased development to the cavitation stage (on day 4); whereas in B⁰AT1 knockout embryos Pro improved development to the 5–8-cell (day 3) and blastocyst stages (day 6) but not at cavitation (day 4), suggesting B⁰AT1 is the main contributor to Pro uptake on day 4 of development. Our results highlight transporter redundancy in the preimplantation embryo. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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21 pages, 3458 KiB

Open AccessArticle

Identification of the Inner Cell Mass and the Trophectoderm Responses after an In Vitro Exposure to Glucose and Insulin during the Preimplantation Period in the Rabbit Embryo

by Romina Via y Rada, Nathalie Daniel, Catherine Archilla, Anne Frambourg, Luc Jouneau, Yan Jaszczyszyn, Gilles Charpigny, Véronique Duranthon and Sophie Calderari

Cells 2022, 11(23), 3766; https://doi.org/10.3390/cells11233766 - 25 Nov 2022

Cited by 2 | Viewed by 1696

Abstract

The prevalence of metabolic diseases is increasing, leading to more women entering pregnancy with alterations in the glucose-insulin axis. The aim of this work was to investigate the effect of a hyperglycemic and/or hyperinsulinemic environment on the development of the preimplantation embryo. In [...] Read more.

The prevalence of metabolic diseases is increasing, leading to more women entering pregnancy with alterations in the glucose-insulin axis. The aim of this work was to investigate the effect of a hyperglycemic and/or hyperinsulinemic environment on the development of the preimplantation embryo. In rabbit embryos developed in vitro in the presence of high insulin (HI), high glucose (HG), or both (HGI), we determined the transcriptomes of the inner cell mass (ICM) and the trophectoderm (TE). HI induced 10 differentially expressed genes (DEG) in ICM and 1 in TE. HG ICM exhibited 41 DEGs involved in oxidative phosphorylation (OXPHOS) and cell number regulation. In HG ICM, proliferation was decreased (p < 0.01) and apoptosis increased (p < 0.001). HG TE displayed 132 DEG linked to mTOR signaling and regulation of cell number. In HG TE, proliferation was increased (p < 0.001) and apoptosis decreased (p < 0.001). HGI ICM presented 39 DEG involved in OXPHOS and no differences in proliferation and apoptosis. HGI TE showed 16 DEG linked to OXPHOS and cell number regulation and exhibited increased proliferation (p < 0.001). Exposure to HG and HGI during preimplantation development results in common and specific ICM and TE responses that could compromise the development of the future individual and placenta. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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22 pages, 4644 KiB

Open AccessArticle

ROCK Inhibitor (Y-27632) Abolishes the Negative Impacts of miR-155 in the Endometrium-Derived Extracellular Vesicles and Supports Embryo Attachment

by Islam M. Saadeldin, Bereket Molla Tanga, Seonggyu Bang, Chaerim Seo, Okjae Koo, Sung Ho Yun, Seung Il Kim, Sanghoon Lee and Jongki Cho

Cells 2022, 11(19), 3178; https://doi.org/10.3390/cells11193178 - 10 Oct 2022

Cited by 5 | Viewed by 2045

Abstract

Extracellular vesicles (EVs) are nanosized vesicles that act as snapshots of cellular components and mediate cellular communications, but they may contain cargo contents with undesired effects. We developed a model to improve the effects of endometrium-derived EVs (Endo-EVs) on the porcine embryo attachment [...] Read more.

Extracellular vesicles (EVs) are nanosized vesicles that act as snapshots of cellular components and mediate cellular communications, but they may contain cargo contents with undesired effects. We developed a model to improve the effects of endometrium-derived EVs (Endo-EVs) on the porcine embryo attachment in feeder-free culture conditions. Endo-EVs cargo contents were analyzed using conventional and real-time PCR for micro-RNAs, messenger RNAs, and proteomics. Porcine embryos were generated by parthenogenetic electric activation in feeder-free culture conditions supplemented with or without Endo-EVs. The cellular uptake of Endo-EVs was confirmed using the lipophilic dye PKH26. Endo-EVs cargo contained miR-100, miR-132, and miR-155, together with the mRNAs of porcine endogenous retrovirus (PERV) and β-catenin. Targeting PERV with CRISPR/Cas9 resulted in reduced expression of PERV mRNA transcripts and increased miR-155 in the Endo-EVs, and supplementing these in embryos reduced embryo attachment. Supplementing the medium containing Endo-EVs with miR-155 inhibitor significantly improved the embryo attachment with a few outgrowths, while supplementing with Rho-kinase inhibitor (RI, Y-27632) dramatically improved both embryo attachment and outgrowths. Moreover, the expression of miR-100, miR-132, and the mRNA transcripts of BCL2, zinc finger E-box-binding homeobox 1, β-catenin, interferon-γ, protein tyrosine phosphatase non-receptor type 1, PERV, and cyclin-dependent kinase 2 were all increased in embryos supplemented with Endo-EVs + RI compared to those in the control group. Endo-EVs + RI reduced apoptosis and increased the expression of OCT4 and CDX2 and the cell number of embryonic outgrowths. We examined the individual and combined effects of RI compared to those of the miR-155 mimic and found that RI can alleviate the negative effects of the miR-155 mimic on embryo attachment and outgrowths. EVs can improve embryo attachment and the unwanted effects of the de trop cargo contents (miR-155) can be alleviated through anti-apoptotic molecules such as the ROCK inhibitor. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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19 pages, 2725 KiB

Open AccessArticle

Intrachromosomal Looping and Histone K27 Methylation Coordinately Regulates the lncRNA H19-Fetal Mitogen IGF2 Imprinting Cluster in the Decidual Microenvironment of Early Pregnancy

by Xue Wen, Qi Zhang, Lei Zhou, Zhaozhi Li, Xue Wei, Wang Yang, Jiaomei Zhang, Hui Li, Zijun Xu, Xueling Cui, Songling Zhang, Yufeng Wang, Wei Li, Andrew R. Hoffman, Zhonghui Liu, Ji-Fan Hu and Jiuwei Cui

Cells 2022, 11(19), 3130; https://doi.org/10.3390/cells11193130 - 05 Oct 2022

Cited by 4 | Viewed by 1769

Abstract

Recurrent spontaneous abortion (RSA) is a highly heterogeneous complication of pregnancy with the underlying mechanisms remaining uncharacterized. Dysregulated decidualization is a critical contributor to the phenotypic alterations related to pregnancy complications. To understand the molecular factors underlying RSA, we explored the role of [...] Read more.

Recurrent spontaneous abortion (RSA) is a highly heterogeneous complication of pregnancy with the underlying mechanisms remaining uncharacterized. Dysregulated decidualization is a critical contributor to the phenotypic alterations related to pregnancy complications. To understand the molecular factors underlying RSA, we explored the role of longnoncoding RNAs (lncRNAs) in the decidual microenvironment where the crosstalk at the fetal–maternal interface occurs. By exploring RNA-seq data from RSA patients, we identified H19, a noncoding RNA that exhibits maternal monoallelic expression, as one of the most upregulated lncRNAs associated with RSA. The paternally expressed fetal mitogen IGF2, which is reciprocally coregulated with H19 within the same imprinting cluster, was also upregulated. Notably, both genes underwent loss of imprinting, as H19 and IGF2 were actively transcribed from both parental alleles in some decidual tissues. This loss of imprinting in decidual tissues was associated with the loss of the H3K27m3 repressive histone marker in the IGF2 promoter, CpG hypomethylation at the central CTCF binding site in the imprinting control center (ICR), and the loss of CTCF-mediated intrachromosomal looping. These data suggest that dysregulation of the H19/IGF2 imprinting pathway may be an important epigenetic factor in the decidual microenvironment related to poor decidualization. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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13 pages, 690 KiB

Open AccessArticle

The Effects of a Preconception Lifestyle Intervention on Childhood Cardiometabolic Health—Follow-Up of a Randomized Controlled Trial

by Stijn Mintjens, Mireille N. M. van Poppel, Henk Groen, Annemieke Hoek, Ben Willem Mol, Rebecca C. Painter, Reinoud J. B. J. Gemke and Tessa J. Roseboom

Cells 2022, 11(1), 41; https://doi.org/10.3390/cells11010041 - 24 Dec 2021

Cited by 3 | Viewed by 3441

Abstract

Maternal obesity is associated with adverse metabolic outcomes in her offspring, from the earliest stages of development leading to obesity and poorer cardiometabolic health in her offspring. We investigated whether an effective preconception lifestyle intervention in obese women affected cardiometabolic health of their [...] Read more.

Maternal obesity is associated with adverse metabolic outcomes in her offspring, from the earliest stages of development leading to obesity and poorer cardiometabolic health in her offspring. We investigated whether an effective preconception lifestyle intervention in obese women affected cardiometabolic health of their offspring. We randomly allocated 577 infertile women with obesity to a 6-month lifestyle intervention, or to prompt infertility management. Of the 305 eligible children, despite intensive efforts, 17 in the intervention and 29 in the control group were available for follow-up at age 3–6 years. We compared the child’s Body Mass Index (BMI) Z score, waist and hip circumference, body-fat percentage, blood pressure Z scores, pulse wave velocity and serum lipids, glucose and insulin concentrations. Between the intervention and control groups, the mean (±SD) offspring BMI Z score (0.69 (±1.17) vs. 0.62 (±1.04)) and systolic and diastolic blood pressure Z scores (0.45 (±0.65) vs. 0.54 (±0.57); 0.91 (±0.66) vs. 0.96 (±0.57)) were similar, although elevated compared to the norm population. We also did not detect any differences between the groups in the other outcomes. In this study, we could not detect effects of a preconception lifestyle intervention in obese infertile women on the cardiometabolic health of their offspring. Low follow-up rates, perhaps due to the children’s age or the subject matter, combined with selection bias abating contrast in periconceptional weight between participating mothers, hampered the detection of potential effects. Future studies that account for these factors are needed to confirm whether a preconception lifestyle intervention may improve the cardiometabolic health of children of obese mothers. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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19 pages, 29728 KiB

Open AccessArticle

The Long Terminal Repeats of ERV6 Are Activated in Pre-Implantation Embryos of Cynomolgus Monkey

by Kui Duan, Chen-Yang Si, Shu-Mei Zhao, Zong-Yong Ai, Bao-Hua Niu, Yu Yin, Li-Feng Xiang, Hao Ding and Yun Zheng

Cells 2021, 10(10), 2710; https://doi.org/10.3390/cells10102710 - 09 Oct 2021

Cited by 3 | Viewed by 2299

Abstract

Precise gene regulation is critical during embryo development. Long terminal repeat elements (LTRs) of endogenous retroviruses (ERVs) are dynamically expressed in blastocysts of mammalian embryos. However, the expression pattern of LTRs in monkey blastocyst is still unknown. By single-cell RNA-sequencing (seq) data of [...] Read more.

Precise gene regulation is critical during embryo development. Long terminal repeat elements (LTRs) of endogenous retroviruses (ERVs) are dynamically expressed in blastocysts of mammalian embryos. However, the expression pattern of LTRs in monkey blastocyst is still unknown. By single-cell RNA-sequencing (seq) data of cynomolgus monkeys, we found that LTRs of several ERV families, including MacERV6, MacERV3, MacERV2, MacERVK1, and MacERVK2, were highly expressed in pre-implantation embryo cells including epiblast (EPI), trophectoderm (TrB), and primitive endoderm (PrE), but were depleted in post-implantation. We knocked down MacERV6-LTR1a in cynomolgus monkeys with a short hairpin RNA (shRNA) strategy to examine the potential function of MacERV6-LTR1a in the early development of monkey embryos. The silence of MacERV6-LTR1a mainly postpones the differentiation of TrB, EPI, and PrE cells in embryos at day 7 compared to control. Moreover, we confirmed MacERV6-LTR1a could recruit Estrogen Related Receptor Beta (ESRRB), which plays an important role in the maintenance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF and Wnt signaling pathways. In summary, these results suggest that MacERV6-LTR1a is involved in gene regulation of the pre-implantation embryo of the cynomolgus monkeys. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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21 pages, 18594 KiB

Open AccessArticle

Progressive Domain Segregation in Early Embryonic Development and Underlying Correlation to Genetic and Epigenetic Changes

by Hui Quan, Hao Tian, Sirui Liu, Yue Xue, Yu Zhang, Wei Xie and Yi Qin Gao

Cells 2021, 10(10), 2521; https://doi.org/10.3390/cells10102521 - 23 Sep 2021

Cited by 4 | Viewed by 2449

Abstract

Chromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming, and the corresponding sequence-dependence in both mouse and human embryo development. The two types of domains, identified earlier as [...] Read more.

Chromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming, and the corresponding sequence-dependence in both mouse and human embryo development. The two types of domains, identified earlier as forests (CGI-rich domains) and prairies (CGI-poor domains) based on the uneven distribution of CGI in the genome, become spatially segregated during embryonic development, with the exception of zygotic genome activation (ZGA) and implantation, at which point significant domain mixing occurs. Structural segregation largely coincides with DNA methylation and gene expression changes. Genes located in mixed prairie domains show proliferation and ectoderm differentiation-related function in ZGA and implantation, respectively. The chromatin of the ectoderm shows the weakest and the endoderm the strongest domain segregation in germ layers. This chromatin structure difference between different germ layers generally enlarges upon further differentiation. The systematic chromatin structure establishment and its sequence-based segregation strongly suggest the DNA sequence as a possible driving force for the establishment of chromatin 3D structures that profoundly affect the expression profile. Other possible factors correlated with or influencing chromatin structures, including transcription, the germ layers, and the cell cycle, are discussed for an understanding of concerted chromatin structure and epigenetic changes in development. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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13 pages, 5606 KiB

Open AccessArticle

Hypoblast Formation in Bovine Embryos Does Not Depend on NANOG

by Claudia Springer, Valeri Zakhartchenko, Eckhard Wolf and Kilian Simmet

Cells 2021, 10(9), 2232; https://doi.org/10.3390/cells10092232 - 28 Aug 2021

Cited by 10 | Viewed by 2698

Abstract

The role of the pluripotency factor NANOG during the second embryonic lineage differentiation has been studied extensively in mouse, although species-specific differences exist. To elucidate the role of NANOG in an alternative model organism, we knocked out NANOG in fibroblast cells and produced [...] Read more.

The role of the pluripotency factor NANOG during the second embryonic lineage differentiation has been studied extensively in mouse, although species-specific differences exist. To elucidate the role of NANOG in an alternative model organism, we knocked out NANOG in fibroblast cells and produced bovine NANOG-knockout (KO) embryos via somatic cell nuclear transfer (SCNT). At day 8, NANOG-KO blastocysts showed a decreased total cell number when compared to controls from SCNT (NT Ctrl). The pluripotency factors OCT4 and SOX2 as well as the hypoblast (HB) marker GATA6 were co-expressed in all cells of the inner cell mass (ICM) and, in contrast to mouse Nanog-KO, expression of the late HB marker SOX17 was still present. We blocked the MEK-pathway with a MEK 1/2 inhibitor, and control embryos showed an increase in NANOG positive cells, but SOX17 expressing HB precursor cells were still present. NANOG-KO together with MEK-inhibition was lethal before blastocyst stage, similarly to findings in mouse. Supplementation of exogenous FGF4 to NANOG-KO embryos did not change SOX17 expression in the ICM, unlike mouse Nanog-KO embryos, where missing SOX17 expression was completely rescued by FGF4. We conclude that NANOG mediated FGF/MEK signaling is not required for HB formation in the bovine embryo and that another—so far unknown—pathway regulates HB differentiation. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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16 pages, 2248 KiB

Open AccessArticle

In Vitro Fertilisation of Mouse Oocytes in L-Proline and L-Pipecolic Acid Improves Subsequent Development

by Tamara Treleaven, Madeleine L.M. Hardy, Michelle Guttman-Jones, Michael B. Morris and Margot L. Day

Cells 2021, 10(6), 1352; https://doi.org/10.3390/cells10061352 - 29 May 2021

Cited by 13 | Viewed by 2928

Abstract

Exposure of oocytes to specific amino acids during in vitro fertilisation (IVF) improves preimplantation embryo development. Embryos fertilised in medium with proline and its homologue pipecolic acid showed increased blastocyst formation and inner cell mass cell numbers compared to embryos fertilised in medium [...] Read more.

Exposure of oocytes to specific amino acids during in vitro fertilisation (IVF) improves preimplantation embryo development. Embryos fertilised in medium with proline and its homologue pipecolic acid showed increased blastocyst formation and inner cell mass cell numbers compared to embryos fertilised in medium containing no amino acids, betaine, glycine, or histidine. The beneficial effect of proline was prevented by the addition of excess betaine, glycine, and histidine, indicating competitive inhibition of transport-mediated uptake. Expression of transporters of proline in oocytes was investigated by measuring the rate of uptake of radiolabelled proline in the presence of unlabelled amino acids. Three transporters were identified, one that was sodium-dependent, PROT (SLC6A7), and two others that were sodium-independent, PAT1 (SLC36A1) and PAT2 (SLC36A2). Immunofluorescent staining showed localisation of PROT in intracellular vesicles and limited expression in the plasma membrane, while PAT1 and PAT2 were both expressed in the plasma membrane. Proline and pipecolic acid reduced mitochondrial activity and reactive oxygen species in oocytes, and this may be responsible for their beneficial effect. Overall, our results indicate the importance of inclusion of specific amino acids in IVF medium and that consideration should be given to whether the addition of multiple amino acids prevents the action of beneficial amino acids. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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Review

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16 pages, 1296 KiB

Open AccessReview

Ultrastructural Evaluation of the Human Oocyte at the Germinal Vesicle Stage during the Application of Assisted Reproductive Technologies

by Maria Grazia Palmerini, Sevastiani Antonouli, Guido Macchiarelli, Sandra Cecconi, Serena Bianchi, Mohammad Ali Khalili and Stefania Annarita Nottola

Cells 2022, 11(10), 1636; https://doi.org/10.3390/cells11101636 - 13 May 2022

Cited by 4 | Viewed by 2325

Abstract

After its discovery in 1825 by the physiologist J.E. Purkinje, the human germinal vesicle (GV) attracted the interest of scientists. Discarded after laparotomy or laparoscopic ovum pick up from the pool of retrieved mature oocytes, the leftover GV was mainly used for research [...] Read more.

After its discovery in 1825 by the physiologist J.E. Purkinje, the human germinal vesicle (GV) attracted the interest of scientists. Discarded after laparotomy or laparoscopic ovum pick up from the pool of retrieved mature oocytes, the leftover GV was mainly used for research purposes. After the discovery of Assisted Reproductive Technologies (ARTs) such as in vitro maturation (IVM), in vitro fertilization and embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI), its developing potential was explored, and recognized as an important source of germ cells, especially in the case of scarce availability of mature oocytes for pathological/clinical conditions or in the case of previous recurrent implantation failure. We here review the ultrastructural data available on GV-stage human oocytes and their application to ARTs. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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18 pages, 2045 KiB

Open AccessEditor’s ChoiceReview

The Role of Mitochondria in Human Fertility and Early Embryo Development: What Can We Learn for Clinical Application of Assessing and Improving Mitochondrial DNA?

by Amira Podolak, Izabela Woclawek-Potocka and Krzysztof Lukaszuk

Cells 2022, 11(5), 797; https://doi.org/10.3390/cells11050797 - 24 Feb 2022

Cited by 20 | Viewed by 5978

Abstract

Mitochondria are well known as ‘the powerhouses of the cell’. Indeed, their major role is cellular energy production driven by both mitochondrial and nuclear DNA. Such a feature makes these organelles essential for successful fertilisation and proper embryo implantation and development. Generally, mitochondrial [...] Read more.

Mitochondria are well known as ‘the powerhouses of the cell’. Indeed, their major role is cellular energy production driven by both mitochondrial and nuclear DNA. Such a feature makes these organelles essential for successful fertilisation and proper embryo implantation and development. Generally, mitochondrial DNA is exclusively maternally inherited; oocyte’s mitochondrial DNA level is crucial to provide sufficient ATP content for the developing embryo until the blastocyst stage of development. Additionally, human fertility and early embryogenesis may be affected by either point mutations or deletions in mitochondrial DNA. It was suggested that their accumulation may be associated with ovarian ageing. If so, is mitochondrial dysfunction the cause or consequence of ovarian ageing? Moreover, such an obvious relationship of mitochondria and mitochondrial genome with human fertility and early embryo development gives the field of mitochondrial research a great potential to be of use in clinical application. However, even now, the area of assessing and improving DNA quantity and function in reproductive medicine drives many questions and uncertainties. This review summarises the role of mitochondria and mitochondrial DNA in human reproduction and gives an insight into the utility of their clinical use. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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18 pages, 623 KiB

Open AccessFeature PaperReview

Amino Acid Transport and Metabolism Regulate Early Embryo Development: Species Differences, Clinical Significance, and Evolutionary Implications

by Lon J. Van Winkle

Cells 2021, 10(11), 3154; https://doi.org/10.3390/cells10113154 - 13 Nov 2021

Cited by 13 | Viewed by 2802

Abstract

In this review we discuss the beneficial effects of amino acid transport and metabolism on pre- and peri-implantation embryo development, and we consider how disturbances in these processes lead to undesirable health outcomes in adults. Proline, glutamine, glycine, and methionine transport each foster [...] Read more.

In this review we discuss the beneficial effects of amino acid transport and metabolism on pre- and peri-implantation embryo development, and we consider how disturbances in these processes lead to undesirable health outcomes in adults. Proline, glutamine, glycine, and methionine transport each foster cleavage-stage development, whereas leucine uptake by blastocysts via transport system B^0,+ promotes the development of trophoblast motility and the penetration of the uterine epithelium in mammalian species exhibiting invasive implantation. (Amino acid transport systems and transporters, such as B^0,+, are often oddly named. The reader is urged to focus on the transporters’ functions, not their names.) B^0,+ also accumulates leucine and other amino acids in oocytes of species with noninvasive implantation, thus helping them to produce proteins to support later development. This difference in the timing of the expression of system B^0,+ is termed heterochrony—a process employed in evolution. Disturbances in leucine uptake via system B^0,+ in blastocysts appear to alter the subsequent development of embryos, fetuses, and placentae, with undesirable consequences for offspring. These consequences may include greater adiposity, cardiovascular dysfunction, hypertension, neural abnormalities, and altered bone growth in adults. Similarly, alterations in amino acid transport and metabolism in pluripotent cells in the blastocyst inner cell mass likely lead to epigenetic DNA and histone modifications that produce unwanted transgenerational health outcomes. Such outcomes might be avoided if we learn more about the mechanisms of these effects. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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23 pages, 1966 KiB

Open AccessReview

Challenges and Considerations during In Vitro Production of Porcine Embryos

by Paula R. Chen, Bethany K. Redel, Karl C. Kerns, Lee D. Spate and Randall S. Prather

Cells 2021, 10(10), 2770; https://doi.org/10.3390/cells10102770 - 15 Oct 2021

Cited by 19 | Viewed by 6170

Abstract

Genetically modified pigs have become valuable tools for generating advances in animal agriculture and human medicine. Importantly, in vitro production and manipulation of embryos is an essential step in the process of creating porcine models. As the in vitro environment is still suboptimal, [...] Read more.

Genetically modified pigs have become valuable tools for generating advances in animal agriculture and human medicine. Importantly, in vitro production and manipulation of embryos is an essential step in the process of creating porcine models. As the in vitro environment is still suboptimal, it is imperative to examine the porcine embryo culture system from several angles to identify methods for improvement. Understanding metabolic characteristics of porcine embryos and considering comparisons with other mammalian species is useful for optimizing culture media formulations. Furthermore, stressors arising from the environment and maternal or paternal factors must be taken into consideration to produce healthy embryos in vitro. In this review, we progress stepwise through in vitro oocyte maturation, fertilization, and embryo culture in pigs to assess the status of current culture systems and address points where improvements can be made. Full article

(This article belongs to the Special Issue Molecular and Clinical Advances in Understanding Early Embryo Development)

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