1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Increased serine synthesis in cumulus cells of young infertile women with diminished ovarian reserve

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          STUDY QUESTION

          What are the differences in gene expression of cumulus cells (CCs) between young women with diminished ovarian reserve (DOR) and those of similar age with normal ovarian reserve (NOR)?

          SUMMARY ANSWER

          Gene expression and metabolome profiling analysis demonstrate that the de novo serine synthesis pathway (SSP) is increased in the CCs of young women with DOR.

          WHAT IS KNOWN ALREADY

          The incidence of DOR has risen, tending to present at younger ages. Its mechanisms and aetiologies are still poorly understood. Abnormal metabolism is present in luteinized CCs of patients with DOR. Previous studies have revealed that mitochondrial dysfunction and impaired oxidative phosphorylation in CCs are related to DOR in women of advanced age. The pathogenic mechanisms likely differ between young women with DOR and cases associated with advanced maternal age. Several studies have examined amino acid metabolism in the follicle, with a focus on embryo development, but less information is available about CCs. The physiological significance of de novo serine synthesis in follicles and oocytes remains largely unknown.

          STUDY DESIGN, SIZE, DURATION

          CC samples were obtained from 107 young infertile women (age <38 years) undergoing ICSI, from July 2017 to June 2019, including 54 patients with DOR and 53 patients with NOR.

          PARTICIPANTS/MATERIALS, SETTING, METHODS

          Oocyte development data were analysed retrospectively. Comprehensive genome-wide transcriptomics of CCs was performed. Differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to categorize the functions of the DEGs and identify significantly enriched pathways. The transcript and protein levels of key enzymes involved in serine synthesis were verified in additional samples using quantitative real-time PCR (qRT-PCR) (n = 10) and capillary western blotting (n = 36). Targeted metabolomics of amino acids in CC extracts was performed by ultrahigh-performance liquid MS (UHPLC–MS/MS).

          MAIN RESULTS AND THE ROLE OF CHANCE

          The number of oocytes (2.4 ± 2.2 versus 12.1 ± 5.3) and metaphase II oocytes (2.1 ± 2.0 versus 9.9 ± 4.9) retrieved was significantly decreased in the DOR versus the NOR group, respectively ( P < 0.0001). The rates of fertilization (80.7% versus 78.8%), viable embryos (73.7% versus 72.5%), and high-quality embryos (42.8% versus 49.0%) did not differ between the DOR and NOR groups, respectively ( P > 0.05). A total of 95 DEGs were found by transcriptome sequencing. GO and KEGG analyses demonstrated that the DEGs were linked to amino acid metabolism and suggested significantly higher activity of the de novo SSP in the CCs of young women with DOR. Further qRT-PCR and capillary western blotting revealed that key enzymes (PHGDH, PSAT1, PSPH, and SHMT2) involved in de novo serine synthesis were upregulated, and UHPLC–MS/MS analysis showed increases in serine and glycine (a downstream product of serine) levels in the CCs of young patients with DOR. Our data clearly demonstrate that the de novo SSP, which diverts 3-phosphoglycerate from glycolysis to serine synthesis, was upregulated in young DOR CCs.

          LARGE SCALE DATA

          N/A.

          LIMITATIONS, REASONS FOR CAUTION

          Regarding the reproductive capacity of young patients DOR, the pregnancy outcomes were not analysed. The sample size was limited, and only women undergoing ICSI were examined since this was a prerequisite for the acquisition of CCs, which may cause selection bias. The exact mechanisms by which the SSP in CCs regulates ovarian reserve still require further study.

          WIDER IMPLICATIONS OF THE FINDINGS

          Our research presents new evidence that alterations of the SSP in CCs of young infertile women are associated with DOR. We believe this is a significant contribution to the field, which should be key for understanding the cause and mechanisms of ovarian hypofunction in young women.

          STUDY FUNDING/COMPETING INTEREST(S)

          This work was supported by grants from the Ministry of Science and Technology of China (2018YFC1005001) and National Natural Science Foundation of China (31601197). There were no competing interests.

          TRIAL REGISTRATION NUMBER

          N/A.

          Related collections

          Most cited references46

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            HTSeq—a Python framework to work with high-throughput sequencing data

            Motivation: A large choice of tools exists for many standard tasks in the analysis of high-throughput sequencing (HTS) data. However, once a project deviates from standard workflows, custom scripts are needed. Results: We present HTSeq, a Python library to facilitate the rapid development of such scripts. HTSeq offers parsers for many common data formats in HTS projects, as well as classes to represent data, such as genomic coordinates, sequences, sequencing reads, alignments, gene model information and variant calls, and provides data structures that allow for querying via genomic coordinates. We also present htseq-count, a tool developed with HTSeq that preprocesses RNA-Seq data for differential expression analysis by counting the overlap of reads with genes. Availability and implementation: HTSeq is released as an open-source software under the GNU General Public Licence and available from http://www-huber.embl.de/HTSeq or from the Python Package Index at https://pypi.python.org/pypi/HTSeq. Contact: sanders@fs.tum.de
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Trinity: reconstructing a full-length transcriptome without a genome from RNA-Seq data

              Massively-parallel cDNA sequencing has opened the way to deep and efficient probing of transcriptomes. Current approaches for transcript reconstruction from such data often rely on aligning reads to a reference genome, and are thus unsuitable for samples with a partial or missing reference genome. Here, we present the Trinity methodology for de novo full-length transcriptome reconstruction, and evaluate it on samples from fission yeast, mouse, and whitefly – an insect whose genome has not yet been sequenced. Trinity fully reconstructs a large fraction of the transcripts present in the data, also reporting alternative splice isoforms and transcripts from recently duplicated genes. In all cases, Trinity performs better than other available de novo transcriptome assembly programs, and its sensitivity is comparable to methods relying on genome alignments. Our approach provides a unified and general solution for transcriptome reconstruction in any sample, especially in the complete absence of a reference genome.
                Bookmark

                Author and article information

                Contributors
                Journal
                Hum Reprod
                Hum Reprod
                humrep
                Human Reproduction (Oxford, England)
                Oxford University Press
                0268-1161
                1460-2350
                September 2023
                02 August 2023
                02 August 2023
                : 38
                : 9
                : 1723-1732
                Affiliations
                Center for Reproductive Medicine, Zhongshan Hospital, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Pharmacy School, Fudan University , Shanghai, China
                State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences , Shanghai, China
                Center for Reproductive Medicine, Zhongshan Hospital, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Pharmacy School, Fudan University , Shanghai, China
                Center for Reproductive Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine , Shanghai, China
                Department of Basic Medical Science, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University , Bangkok, Thailand
                Center for Reproductive Medicine, Zhongshan Hospital, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Pharmacy School, Fudan University , Shanghai, China
                Center for Reproductive Medicine, Zhongshan Hospital, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Pharmacy School, Fudan University , Shanghai, China
                Center for Reproductive Medicine, Zhongshan Hospital, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Pharmacy School, Fudan University , Shanghai, China
                Center for Reproductive Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine , Shanghai, China
                Author notes
                Correspondence address. Center for Reproductive Medicine, Zhongshan Hospital, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Pharmacy School, Fudan University, Shanghai 200032, China. E-mail: lu.xinmei@ 123456zs-hospital.sh.cn (X.L.); Center for Reproductive Medicine, Zhongshan Hospital, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Pharmacy School, Fudan University, Shanghai 200032, China. E-mail: shihuijuan2011@ 123456163.com (H.S.); Center for Reproductive Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China. E-mail: yubingliu@ 123456tongji.edu.cn (Y.L.)

                Xinmei Lu and Xiaolong Lv contributed equally to this work.

                Author information
                https://orcid.org/0009-0006-7984-8793
                https://orcid.org/0000-0001-9146-5310
                https://orcid.org/0009-0003-5308-4279
                https://orcid.org/0000-0002-6244-9677
                Article
                dead155
                10.1093/humrep/dead155
                10477940
                37533289
                c061d7ed-f952-410b-ae27-fc7ffbff2f77
                © The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 24 April 2022
                : 06 June 2023
                : 13 July 2023
                Page count
                Pages: 15
                Funding
                Funded by: Ministry of Science and Technology of China;
                Award ID: 2018YFC1005001
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 31601197
                Categories
                Original Article
                Infertility
                AcademicSubjects/MED00905

                Human biology
                young infertile women,diminished ovarian reserve,embryo development,cumulus cells,transcriptome, de novo serine synthesis,ultrahigh-performance liquid chromatography–tandem mass spectrometry,serine

                Comments

                Comment on this article