Yu Tian
Yu-fan Wang1
Yi-liang Miao
Li-quan Zhou- 1Institute of Reproductive Health/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- 2Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
Editorial on the Research Topic
Fertilization and early development: genetics and epigenetics
Fertilization and early development are processes characterized by delicate genetic and epigenetic regulation. In brief, sperm fuses with the oocyte to form a zygote, which then undergoes zygotic genome activation (ZGA) and lineage specification, ultimately implanting during the blastocyst stage. This process is intricately regulated by numerous key regulatory genes and critical epigenetic modifications, which are vital for the post-implantation development and subsequent pregnancy. This Research Topic comprises three original studies, one case report, and two reviews, which will advance our understanding of genetics and epigenetics in the fertilization and early embryonic development.
Germ cell maturation and embryo development require the precise gene expression program at different developmental stage, which sculpts the dynamic epigenetic modification landscape. Polycomb group (PcG) complex, with its two components PRC1 and PRC2, catalyzes the H2AK119ub1 and H3K27me3, which regulate cell fate by repressing gene expression. Li et al. reviewed the role of the PcG complex in mammalian development, contributing to our understanding of multifaceted functions of the PcG complex and H3K27me3. Additionally, H3K27me3 may be responsible for marking recurrent double-strand breaks (DSBs) in transgenerational DNA repair. Due to the absence of sister chromatids, the genome of haploid round spermatids cannot repair DSBs through homologous recombination repair (Kitaoka and Yamashita, 2024). How spermatids cope with this vulnerable genome state remains not fully elucidated. Scheuren et al. focused on the distribution of DSBs in human sperm, revealing a strong colocalization between H3K27me3 and recurrent DSBs. This result suggests the paternal H3K27me3 may serve as a guiding marker for maternal Polθ in the zygote to execute transgenerational DNA repair at sites of recurrent DSBs.
Following meiosis, round spermatids undergo intricate morphological changes to form mature spermatozoa. Abnormal sperm structures could prevent sperm from approaching or fusing with the oocyte, which is a key cause of fertilization failure. With the application of whole-genome sequencing, many genes associated with teratozoospermia have been identified. Bragina et al. analyzed samples from 12 globozoospermia patients and detected homozygous variants in Dpy19l2 and Spata16 in three of these cases. Mutations in Dpy19l2 and Spata16 have been identified as key causes of globozoospermia (Dam et al., 2007; Koscinski et al., 2011). Moreover, globozoospermia phenotype has also been validated in mouse with Dpy19l2 or Spata16 deficiency (Fujihara et al., 2017; Castaneda et al., 2021). Genetically engineered mouse models offer a pathway for studying the mechanisms of genetic diseases. However, because of the complexity of gene mutation and homology differences, mouse models may not always accurately mimic human phenotypes. Nguyen et al. conducted loss-of-function studies in mouse model on 13 testis-enriched genes including Adam20 (A gene associated with fertilization failure in human), demonstrating that these genes are not essential for male fertility in mice. Therefore, we should cautiously evaluate the results derived from mouse models.
Currently, assisted reproductive technologies are widely used to address fertilization failure and to prevent the transmission of pathogenic parental genes to offspring (Brezina and Kutteh, 2015). Hu et al. firstly reported a woman with Hereditary Leiomyomatosis and Renal Cell Cancer syndrome who successfully delivered a healthy baby by preimplantation genetic testing for monogenic disorders (PGT-M). This case highlights the potential of PGT-M in addressing the reproductive needs of patients with genetic diseases. Apart from genetic defects, environmental pollutants can indirectly impair fertility by affecting gene expression and epigenetics (Green et al., 2021). Wang et al. discussed the reproductive toxicity of endocrine-disrupting chemicals (EDCs) in female reproduction, summarizing the current epidemiological studies and animal model studies for five major EDCs. Environmental pollutants can induce epigenetic alterations through oxidative stress and DNA damage, leading to impaired gene regulation and organelles dysfunction in germ cell or embryo (Strazzullo and Matarazzo, 2017; Lopez-Rodriguez et al., 2021). Therefore, healthy populations without genetic defects should also pay attention to the potential reproductive risks posed by environmental pollution.
Finally, we thank all authors for their contributions in the Research Topic. This Research Topic focuses on the genetic and epigenetic regulation of fertilization and early development, a field that has rapidly advanced over the recent years. While the scope of this Research Topic is limited, the progress it covers is exhilarating, as the advances in basic science are indeed contributing to the disease prevention and clinical intervention in reproductive medicine.
Author contributions
YT: Writing–original draft. Y-fW: Writing–original draft. Y-lM: Writing–review and editing. L-qZ: Writing–review and editing.
Funding
The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China (32170820).
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.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Brezina, P. R., and Kutteh, W. H. (2015). Clinical applications of preimplantation genetic testing. Bmj 350, g7611. doi:10.1136/bmj.g7611
Castaneda, J. M., Shimada, K., Satouh, Y., Yu, Z., Devlin, D. J., Ikawa, M., et al. (2021). FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice. J. Cell Sci. 134, jcs259206. doi:10.1242/jcs.259206
Dam, A. H., Koscinski, I., Kremer, J. A., Moutou, C., Jaeger, A. S., Oudakker, A. R., et al. (2007). Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia. Am. J. Hum. Genet. 81, 813–820. doi:10.1086/521314
Fujihara, Y., Oji, A., Larasati, T., Kojima-Kita, K., and Ikawa, M. (2017). Human globozoospermia-related gene Spata16 is required for sperm formation revealed by CRISPR/Cas9-Mediated mouse models. Int. J. Mol. Sci. 18, 2208. doi:10.3390/ijms18102208
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Kitaoka, M., and Yamashita, Y. M. (2024). Running the gauntlet: challenges to genome integrity in spermiogenesis. Nucleus 15, 2339220. doi:10.1080/19491034.2024.2339220
Koscinski, I., Elinati, E., Fossard, C., Redin, C., Muller, J., Velez de La Calle, J., et al. (2011). DPY19L2 deletion as a major cause of globozoospermia. Am. J. Hum. Genet. 88, 344–350. doi:10.1016/j.ajhg.2011.01.018
Lopez-Rodriguez, D., Franssen, D., Bakker, J., Lomniczi, A., and Parent, A. S. (2021). Cellular and molecular features of EDC exposure: consequences for the GnRH network. Nat. Rev. Endocrinol. 17, 83–96. doi:10.1038/s41574-020-00436-3
Keywords: germ cell, fertilization, early development, genetics, epigenetics
Citation: Tian Y, Wang Y-f, Miao Y-l and Zhou L-q (2024) Editorial: Fertilization and early development: genetics and epigenetics. Front. Genet. 15:1465510. doi: 10.3389/fgene.2024.1465510
Received: 16 July 2024; Accepted: 23 July 2024;
Published: 30 July 2024.
Edited and reviewed by:
Michael E. Symonds, University of Nottingham, United KingdomCopyright © 2024 Tian, Wang, Miao and Zhou. 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: Yi-liang Miao, miaoyl@mail.hzau.edu.cn; Li-quan Zhou, zhouliquan@hust.edu.cn