Renee J. Chosed
Shahryar K. Kavoussi
Dara S. Berger3- 1Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC, United States
- 2Austin Fertility and Reproductive Medicine/Westlake IVF, Austin, TX, United States
- 3Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, United States
Editorial on the Research Topic
Molecular and cellular mechanisms in preimplantation IVF-embryo development
The aims of this Frontiers Research Topic were to further our understanding of how the preimplantation embryo develops, and to consider current techniques used to evaluate embryo viability. If we can deepen our understanding of the molecular and cellular events taking place during preimplantation embryo development, we will be closer to identifying new potential molecular markers of embryo viability, which may one day be used to increase the success of in vitro fertilization (IVF).
Much of what is known about human embryo development at the cell and molecular level was discovered in mouse embryos or other animal models. Therefore, understanding the similarities and differences between human embryo development and other animal models is essential in clarifying the molecular steps taking place during human embryo development (reviewed by Bissiere et al., 2023). Researchers often rely on cultured cell lines and stem cells to understand these molecular and cellular events (White and Plachta, 2020). For example, Oh et al. report deriving lineage specific embryonic cell lines from porcine blastocysts to assess gene expression.
For patients undergoing IVF, the embryo selection process for transfer has traditionally relied on morphology metrics, and more recently, genetic analysis of cells, such as preimplantation genetic testing for aneuploidy (PGT-A) from the trophectoderm (reviewed by Harris et al., 2021). Interestingly, advancements in imaging and specifically time-lapse imaging throughout the culture period of preimplantation embryos, have provided new avenues for morphology studies. For example, several recent reports on the presence of cytoplasmic strings (via time-lapse imaging) in preimplantation embryos conceived via IVF have been published that try to link this morphological structure with blastocyst quality and pregnancy outcomes (Ma et al., 2022; Joo et al., 2023). Arguably the most cutting-edge research associated with embryo time-lapse imaging is the application of artificial intelligence (AI) for embryo screening. Using AI as a means of non-invasive embryo screening is a promising area of research yet there is still more to learn before we will see AI routinely used in the clinic (reviewed by Jiang and Bormann, 2023).
Some efforts have focused on using molecular markers from spent media and blastocoel fluid to assess the viability of the preimplantation embryo. Cell-free DNA and the contents of exosomes found in spent embryo culture media have all been studied to try and understand their specific origin from within the preimplantation embryo, and then attempting to clarify what these molecules tell us about the developing embryo (reviewed by Handayani et al., 2023; Saadeldin et al., 2023). The origin of cell-free DNA in the spent media and blastocoel fluid is thought to be from aneuploid cells that underwent apoptosis, yet there has been extensive research to use this cell-free DNA (non-invasive PGT-A) to assess embryo ploidy status that has yielded mixed results (reviewed by García-Pascual et al., 2023; Cinnioglu et al., 2023). Other molecules in the spent embryo culture media can also be detected and potentially serve as markers for embryo viability. For example, Meng et al. report the use of a Raman spectroscopy method to assess the metabolome present in spent embryonic culture media. However, there is still much that is unknown regarding preimplantation embryonic development and measurable indicators of successful embryo transfer.
Xu et al. reported the identification of two genetic variants of the PADI6 gene in two patients who experienced infertility. The PADI6 protein is part of a multi-protein complex that is required for embryo development, specifically zygote gene activation. While this study used a very small sample size, it still highlights the need for further identification of genetic mutations that are associated with genes regulating embryo development. Therefore, identified mutations in a patients may allow for different counseling for women seeking Assisted Reproductive Technologies (ART), as these mutations may predict poor IVF outcomes. If specific poor-IVF-outcome-gene-mutations can be identified, then a future step could be finding ways to alter/fix these mutations in the preimplantation embryo. Yaghoobi et al. propose a strategy to take the molecular knowledge we have regarding embryo implantation to alter gene expression in the trophoblast layer of the developing blastocyst via CRISPR/dCas9 exosome system.
Having a more thorough understanding of the changes taking place in this stage of development may allow for better use and interpretation of biomarkers of embryo viability, therefore increasing IVF success rates.
Author contributions
RC: Conceptualization, Formal Analysis, Investigation, Supervision, Writing–original draft, Writing–review and editing. SK: Conceptualization, Formal Analysis, Investigation, Supervision, Writing–review and editing. DB: Conceptualization, Formal Analysis, Supervision, Writing–review and editing. KM: Formal Analysis, Investigation, Writing–original draft. MG-V: Formal Analysis, Investigation, Supervision, Writing–original draft.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
Bissiere, S., Hernandez, B., Rubio, C., Simón, C., and Plachta, N. (2023). Updates on preimplantation embryo research. Fertil. Steril. May 6, 467–472. doi:10.1016/j.fertnstert.2023.04.039
Cinnioglu, C., Glessner, H., Jordan, A., and Bunshaft, S. (2023). A systematic review of non-invasive preimplantation genetic testing for aneuploidy. Fertil. Steril. 120 (2), 235–239. doi:10.1016/j.fertnstert.2023.06.013
García-Pascual, C. M., Navarro-Sánchez, L., Ichikawa-Ceschin, I., Bakalova, D., Martínez-Merino, L., Simón, C., et al. (2023). Cell-free deoxyribonucleic acid analysis in preimplantation genetic testing. F&S Sci. 4 (2), 7–16. doi:10.1016/j.xfss.2023.01.001
Handayani, N., Aubry, D., Boediono, A., Wiweko, B., Sirait, B., Sini, I., et al. (2023). The origin and possible mechanism of embryonic cell-free DNA release in spent embryo culture media: A review. J. Assist. Reprod. Genet. 40, 1231–1242. doi:10.1007/s10815-023-02813-z
Harris, B. S., Bishop, K. C., Kuller, J. A., Alkilany, S., and Price, T. M. (2021). Preimplantation genetic testing: A review of current modalities. F&S Rev. 2 (1), 43–56. doi:10.1016/j.xfnr.2020.10.001
Jiang, V. S., and Bormann, C. L. (2023). Non-invasive genetic screening: current advances in artificial intelligence for embryo ploidy prediction. Fertil. Steril. 120 (2), 228–234. doi:10.1016/j.fertnstert.2023.06.025
Joo, K., Nemes, A., Dudas, B., Berkes-Bara, E., Murber, A., Urbancsek, J., et al. (2023). The importance of cytoplasmic strings during early human embryonic development. Front. Cell Dev. Biol. 11, 1177279. doi:10.3389/fcell.2023.1177279
Ma, B. X., Yang, L., Tian, Y., Jin, L., and Huang, B. (2022). Cytoplasmic strings between icm and mTE are a positive predictor of clinical pregnancy and live birth outcomes: A time-lapse study. Front. Med. 9, 934327. doi:10.3389/fmed.2022.934327
Saadeldin, I. M., Ehab, S., and Swelum, A. A. (2023). Potential roles of extracellular vesicles as a noninvasive tool for prenatal genetic diagnosis. F&S Sci. 4 (2), 36–43. doi:10.1016/j.xfss.2023.01.002
Keywords: blastocyst, preimplantation embryo, IVF, embryo development, PGT-A
Citation: Chosed RJ, Kavoussi SK, Berger DS, Massman K and Guerra-Velasquez M (2023) Editorial: Molecular and cellular mechanisms in preimplantation IVF-embryo development. Front. Cell Dev. Biol. 11:1279129. doi: 10.3389/fcell.2023.1279129
Received: 17 August 2023; Accepted: 28 August 2023;
Published: 31 August 2023.
Edited and reviewed by:
Shao-Chen Sun, Nanjing Agricultural University, ChinaCopyright © 2023 Chosed, Kavoussi, Berger, Massman and Guerra-Velasquez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Renee J. Chosed, chosed@greenvillemed.sc.edu