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Abstract:
STUDY QUESTION:Does oocyte maturation under lipolytic conditions have detrimental carry-over effects on post-hatching embryo development of good-quality blastocysts after transfer? SUMMARY ANSWER:Surviving, morphologically normal blastocysts derived from bovine oocytes that matured under lipotoxic conditions exhibit long-lasting cellular dysfunction at the transcriptomic and metabolic levels, which coincides with retarded post-hatching embryo development. WHAT IS KNOWN ALREADY:There is increasing evidence showing that following maturation in pathophysiologically relevant lipotoxic conditions (as in obesity or metabolic syndrome), surviving blastocysts of good (transferable) morphological quality have persistent transcriptomic and epigenetic alteration even when in vitro embryo culture takes place under standard conditions. However, very little is known about subsequent development in the uterus after transfer. STUDY DESIGN, SIZE, DURATION:Bovine oocytes were matured in vitro in the presence of pathophysiologically relevant, high non-esterified fatty acid (NEFA) concentrations (HIGH PA), or in basal NEFA concentrations (BASAL) as a physiological control. Eight healthy multiparous non-lactating Holstein cows were used for embryo transfers. Good-quality blastocysts (pools of eight) were transferred per cow, and cows were crossed over for treatments in the next replicate. Embryos were recovered 7 days later and assessed for post-hatching development, phenotypic features and gene expression profile. Blastocysts from solvent-free and NEFA-free maturation (CONTROL) were also tested for comparison. PARTICIPANTS/MATERIALS, SETTING, METHODS:Recovered Day 14 embryos were morphologically assessed and dissected into embryonic disk (ED) and extraembryonic tissue (EXT). Samples of EXT were cultured for 24 h to assess cellular metabolic activity (glucose and pyruvate consumption and lactate production) and embryos' ability to signal for maternal recognition of pregnancy (interferon-τ secretion; IFN-τ). ED and EXT samples were subjected to RNA sequencing to evaluate the genome-wide transcriptome patterns. MAIN RESULTS AND THE ROLE OF CHANCE:The embryo recovery rate at Day 14 p.i. was not significantly different among treatment groups (P > 0.1). However, higher proportions of HIGH PA embryos were retarded in growth (in spherical stage) compared to the more elongated tubular stage embryos in the BASAL group (P < 0.05). Focusing on the normally developed tubular embryos in both groups, HIGH PA exposure resulted in altered cellular metabolism and altered transcriptome profile particularly in pathways related to redox-regulating mechanisms, apoptosis, cellular growth, interaction and differentiation, energy metabolism and epigenetic mechanisms, compared to BASAL embryos. Maturation under BASAL conditions did not have any significant effects on post-hatching development and cellular functions compared to CONTROL. LARGE-SCALE DATA:The datasets of RNA sequencing analysis are available in the NCBI's Gene Expression Omnibus (GEO) repository, series accession number GSE127889 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE127889). Datasets of differentially expressed genes and their gene ontology functions are available in the Mendeley datasets at http://dx.doi.org/10.17632/my2z7dvk9j.2. LIMITATIONS, REASONS FOR CAUTION:The bovine model was used here to allow non-invasive embryo transfer and post-hatching recovery on Day 14. There are physiological differences in some characteristics of post-hatching embryo development between human and cows, such as embryo elongation and trophoblastic invasion. However, the main carry-over effects of oocyte maturation under lipolytic conditions described here are evident at the cellular level and therefore may also occur during post-hatching development in other species including humans. In addition, post-hatching development was studied here under a healthy uterine environment to focus on carry-over effects originating from the oocyte, whereas additional detrimental effects may be induced by maternal metabolic disorders due to adverse changes in the uterine microenvironment. RNA sequencing results were not verified by qPCR, and no solvent control was included. WIDER IMPLICATIONS OF THE FINDINGS:Our observations may increase the awareness of the importance of maternal metabolic stress at the level of the preovulatory oocyte in relation to carry-over effects that may persist in the transferrable embryos. It should further stimulate new research about preventive and protective strategies to optimize maternal metabolic health around conception to maximize embryo viability and thus fertility outcome. STUDY FUNDING/COMPETING INTEREST(S):This study was supported by the Flemish Research Fund (FWO grant 11L8716N and FWO project 42/FAO10300/6541). The authors declare there are no conflicts of interest.
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最新影响因子:6.353 | 期刊ISSN:0268-1161 | CiteScore:4.6 |
出版周期:Monthly | 是否OA:YES | 出版年份:0 |
自引率:9.10% | 研究方向:医学-妇产科学 |
出版地区:ENGLAND |
SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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Human Reproduction features full-length peer-reviewed papers reporting original research clinical case histories as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology endocrinology andrology gonad function gametogenesis fertilization embryo development implantation pregnancy genetics genetic diagnosis oncology infectious disease surgery contraception infertility treatment psychology ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.
人类生殖功能的特点是全文同行评议的论文,报告了原始研究的临床病例历史,以及对专题问题的看法和辩论。论文发表涵盖了生殖生理学和病理学的科学和医学方面的内分泌学、雄激素学、性腺功能配子发生、受精、胚胎发育、植入、遗传学诊断、肿瘤学、传染病、外科、避孕、不孕治疗、心理伦理和社会问题。最高的科学和编辑标准贯穿整个期刊,出版速度也很快。
大类(学科) | 小类(学科) | 学科排名 |
医学 |
OBSTETRICS & GYNECOLOGY (妇产科学) 1区 REPRODUCTIVE BIOLOGY (生殖生物学) 2区 |
4/82 2/29 |
年度总发文量 | 年度论文发表量 | 年度综述发表量 |
276 | 264 | 12 |
引文计数(2018)
文献(2015-2017)
4902次引用
1066篇文献
序号 | 类别 | 排名 | 百分位 |
1 |
大类(学科):Medicine
小类(学科):Reproductive Medicine
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2 |
大类(学科):Medicine
小类(学科):Obstetrics and Gynecology
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#2/168
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研究方向:生物 医学:研究与实验
审稿时间: 1个月内
影响因子:2.566
ISSN:0739-7240
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影响因子:3.492
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研究方向:CLINICAL NEUROLOGY-PSYCHIATRY
影响因子:4.562
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研究方向:医学-精神病学
影响因子:6.533
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研究方向:医学-精神病学
影响因子:5.415
ISSN:0924-977X
研究方向:医学-精神病学
发表一篇学和医学成像类SCI论文
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