The role of zygotic genome activation in genetic−related reproductive medicine: Technological perspective, religious and bioethical concerns, challenges and benefits

Highlights

• •Religious scholars take a generally favorable position toward human genome editing research, and Gulf countries have launched several scientific efforts on the topic, especially gene editing in assisted reproductive technology (ART).
• •Recent improvements with regard to human genetic and reproduction techniques are among the recent discoveries that are disrupting the balance of life's spiritual and material components.
• •The Islamic stance on abortion, in vitro fertilization, genetic engineering, cloning, and stem cell research, especially ZGA.
• •We identified many likely distinct transcriptional activities characterizing the zygotic genome at ZGA onset.
• •Epigenetic reprogramming promotes major ZGA in various embryos.

Abstract

Zygotic Genome Activation (ZGA) is a crucial developmental milestone in early embryogenesis, marking the transition from maternal to embryonic control of development. This process, which varies in timing across species, involves the activation of the embryonic genome, paving the way for subsequent cell differentiation and organismal development. Recent advances in genomics and reproductive medicine have highlighted the potential of ZGA in the realm of genetic screening, providing a window into the genetic integrity of the developing embryo at its earliest stages. The intersection of ZGA and genetic screening primarily emerges in the context of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). These techniques, often employed during assisted reproductive technologies, aim to detect potential genetic abnormalities or chromosomal imbalances before embryo implantation. Given that ZGA represents the onset of embryonic gene expression, understanding its intricacies can significantly enhance the accuracy and predictive power of these screening processes. With the advent of next-generation sequencing and other high-throughput genomic techniques, detailed mapping of the transcriptomic changes during ZGA has become feasible. Such advancements have deepened our insights into the dynamics of early embryonic development and the onset of genetic disorders. As our knowledge in this realm expands, it promises to revolutionize our capabilities in detecting, understanding, and potentially rectifying genetic anomalies at the earliest stages of human life, thereby optimizing reproductive outcomes.

1. Introduction

The advancement of genetic technology has enabled the modification of somatic and germ cells.1, 2 Recently, scientists employed gene editing technologies to effectively modify the human fetal genome.3, 4 During the past several decades, researchers have concentrated on the applications of gene editing in the human zygote to address genetic illnesses such as human tri pronuclear zygotes.5, 6, 7 The editing of genes is a method for inserting, deleting, or changing genetic material at a particular spot in the genetic code.⁸ CRISPR-Cas9 (clustered, frequently separated small palindromic repeats, related protein 9) represents one of several genome editing methods that are more precise, faster, less expensive, and more effective compared to other genome editing techniques now available.⁹ Zygotic Genome Activation (ZGA) is a critical stage in early embryonic development that marks the change from reliance on maternal genetic instructions to the start of the embryo's genomic expression.¹⁰ This complicated system starts after fertilization when the embryo begins to create the groundwork for its distinct genetic identity. As a result, ZGA is critical in the development of the embryo. As we learn more about ZGA and how to regulate its complexities, new potential for genetic and personalized treatment arises, particularly in reproductive medicine.¹¹ These possibilities have substantial implications for the early diagnosis of possible genetic abnormalities and open the door for considerable advances in reproductive and genetic medicine.¹²

Embryo development is a complicated series of cellular activities that begins with fertilization and culminates in the formation of a full creature.¹³ The transfer from maternal to zygotic control, which happens during ZGA, is important to this process. Before this shift, maternal mRNAs and proteins regulate the first cell divisions after fertilization.¹⁴ The zygotic genome does not become transcriptionally active until ZGA occurs, enabling the embryo to grow according to its genetic profile. This stage of development is critical because it determines the genetic blueprint of the particular organism.

The overarching concept of Maqasid al-Shari'a, which relates to the Goals of Islamic Law, as well as the main Fiqhi (Islamic Jurisprudential) maxims, serves as the cornerstone of Islamic bioethics.¹⁵ These principles work as a guide to morality, directing ethical judgements to ensure that behaviours accord with and do not conflict with these goals.

However, modern ethical quandaries, such as those arising from advances in genetic technology such as gene editing, may not always be explicitly addressed in core Islamic writings such as the Quran and Sunnah. To resolve these challenges, Muslim academics resort to alternate Shari'a sources, such as the idea of ijma' (scholarly consensus) and qiyas (logical analogy), for guidance and making informed ethical judgements.¹⁶

Concerns about the possible dangers of gene editing, in particular, have fueled the debate. These dangers include the potential of unexpected modifications to the DNA sequence or structure, which might result in accidental edits in the incorrect places or mosaicism, in which edited and unedited cells coexist.¹⁷ Furthermore, germline gene editing presents the added issue that the genetic changes performed in these cells may be passed down to future generations.

The Islamic framework relies on its fundamental principles and supplemental sources to promote a considered and ethically based approach to the appropriate use of genetic technology in negotiating these complex bioethical difficulties.

Discussions among renowned scientists regarding potential ethical difficulties with gene editing and how it would affect future generations raise worldwide worries about challenges such as designer babies.¹⁸ The degree to which scientists have achieved employing gene editing in humans underlines the need for ethical norms to govern this field of research.19, 20, 21 Scientists believe a treatment may be found at the somatic cell level since genome editing in germ cells might result in unanticipated effects.²² As a result, experts agree that developing ethical criteria for future human genetic engineering research is critical.²³ Indeed, because of the rapid advancements in gene editing, ethical difficulties are being exacerbated by the emergence of new questions. The moral dilemma of embryonic editing genes involves guaranteeing moral principles and ethical norms are not broken. One of the primary ethical difficulties with this technology is informed permission; acquiring a good consent form from the individual undergoing the operation is difficult because the parents decide to employ the procedure on embryos. Furthermore, the unknown risks of germline editing might have an influence on the child's health and children.²⁴

In recent years, significant advancements in genomics and reproductive medicine have altered our ability to research ZGA and its implications for genetic screening.²⁵ For example, next-generation sequencing (NGS) methods provide a high-resolution view of the genome, allowing researchers to trace transcriptome alterations during ZGA in unprecedented depth.²⁶ These developments have increased the precision and effectiveness of genetic screening and our knowledge of early embryonic development and the beginning of genetic diseases.²⁷

Minor ZGA (mZGA) and major ZGA (MZGA) studies are especially notable since they have offered insight into when and how various sets of genes are activated in the zygote.²⁸ Understanding these sequences and patterns of gene activation might give vital insights into the beginning of genetic disorders, perhaps allowing us to identify, diagnose, and even intervene in genetic anomalies at the earliest stages of human life. ZGA research is essential in developmental biology, reproductive medicine, and genetic screening. We may see the earliest genetic manifestation of life via the lens of ZGA, illuminating the complicated and intriguing journey that each creature takes from a single cell to a whole person. We may anticipate a more thorough knowledge of ZGA as science and technology develop, allowing us to more effectively screen for, diagnose, and possibly correct genetic anomalies. ZGA has enormous promise for the future of genetic medicine, and the quest to realize its full potential is only starting.

The article aims to investigate the essential function of ZGA in the context of newly established genetic technology, bioethics, and religious issues, as well as its advantages and disadvantages. With ZGA as a critical developmental process, the goal is to understand better its dynamics, the consequences for early embryonic development, and its potential use in improving genetic screening approaches. This article examines and synthesizes the scientific literature on ZGA, focusing on its transition phase from maternal to embryonic control and species-specific temporal differences. This extensive paper of ZGA aims to identify possible markers that might help with genetic screening approaches, namely preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Furthermore, next-generation sequencing technology allows for mapping transcriptome alterations during ZGA, providing a high-resolution picture of the genome. This article will use new technology to understand better ZGA and its influence on early embryonic development and the start of genetic disorders. We want to add to the scientific knowledge base via this endeavor, perhaps revolutionizing the early diagnosis and understanding of genetic illnesses. Ultimately, the goal is to enhance reproductive outcomes through genetic screening, favorably improving human health and well-being.

2. Methodology

The approach that was used for this study was rigorous and all-encompassing. It aimed to explore the complex function of ZGA within the context of genetic screening. The article aims to shed light on the molecular processes that drive ZGA and characterize the consequential consequences of these mechanisms for identifying and understanding genetic disorders. An exhaustive examination of the relevant previous literature, stringent data collecting and analysis, and a novel exploratory study that uses in vitro model organisms make up the many components of the overall research plan, which is complex.

2.1. Literature review

The foundation of our paper is a thorough literature evaluation aiming at collecting and refining current information about ZGA. Recognizing the critical function ZGA plays in the early stages of embryonic development, the first objective is to establish a comprehensive knowledge of how this process occurs, emphasizing the shift from maternal to zygotic control. We want to improve our understanding of the key moment when the embryo begins to guide its growth based on its unique genetic makeup autonomously. Furthermore, our literature analysis examines the differences in ZGA timing across various species. The fact that ZGA begins at the two-cell stage in mice but not until the four- to eight-cell stage in humans provides important insights into the complexity of genomic activation. The goal is to distill these variances and consider their consequences for research and the scientific community. The relevance of ZGA for genetic screening approaches is central to our paper. We are investigating this topic to determine the significance of comprehending ZGA in effectively interpreting genetic information, especially for PGD and PGS. Finally, considering the spectacular technological advances, the literature review considers the advances achieved by next-generation sequencing (NGS) and other cutting-edge techniques. Their capacity to give a detailed and high-resolution image of the genome during ZGA is being assessed, allowing us to investigate their potential for improving genetic screening approaches. In summary, the literature evaluation tries to map the current ZGA knowledge environment, laying the groundwork for our subsequent research trip.

2.2. Data collection and analysis

Following the outcome of the detailed literature review, the study moves on to the data collecting and complete analysis phase. This method extracts raw data from well-known and open-source genomic datasets. These databases house information gathered from various research investigations and provide various data that may assist in understanding the dynamics of ZGA. Data collection will be focused on compiling datasets that give insights into transcriptome modifications that occur during ZGA. This information, mostly derived from high-throughput sequencing methods, will reveal gene expression patterns at various embryonic stages, emphasizing alterations that correlate with the zygotic genome beginning. Closely investigating these data sets may reveal the complexity of this basic shift, providing a microscopic glimpse of the genetic modulations throughout this critical developmental stage. However, more than raw data is required to yield clear results. As a result, rigorous data analysis becomes critical. It entails sifting through much data using cutting-edge bioinformatics tools and statistically sound approaches. The goal is to identify identifiable patterns in the data, converting complicated genetic information into usable knowledge. Furthermore, careful statistical analysis will assure the accuracy and precision of the findings, reducing any biases or inaccuracies. The article aims to derive major findings regarding the significance of ZGA in genetic screening through rigorous data collection and analysis, therefore considerably adding to this critical field of study.

2.3. In vitro study

The in vitro study, which uses mice and people as model organisms, is critical to this research initiative. These species were selected because they have solid experimental techniques essential to reproductive biology. This novel exploratory work carried out in a strictly controlled laboratory environment, attempts to replicate and investigate the ZGA process. ZGA initiates the embryonic shift from dependence on maternal genetic programming to activation of its innate genetic design. Given its importance in embryogenesis, a better knowledge of ZGA may be key to understanding early developmental patterns and associated hereditary diseases. The work aims to track the transcriptome changes during this critical development period by recreating the ZGA mechanism in vitro. These changes, characterized by the commencement of zygote genetic expression, will likely yield important insights into the molecular processes underpinning early embryonic development.

Furthermore, the project intends to investigate the sequential activation of several gene clusters throughout the minor and major ZGA stages. The minor ZGA usually comes before the main phase and includes the activation of a small number of genes. The main ZGA begins a larger, more profound genomic activation, leading to further differentiation and development. Understanding the sequence and pattern of these activations might provide deep insights into the early phases of development and, when paired with genetic screening approaches, could improve our ability to identify and comprehend hereditary illnesses from their genesis.

2.4. Integration of ZGA with genetic screening techniques

The main of this paper is devoted to incorporating knowledge of Zygotic Genome Activation into current genetic screening procedures. The goal is to improve the potential of preimplantation genetic diagnosis, or PGD, and preimplantation genetic screening (PGS), two procedures widely utilized in assisted reproduction. ZGA is when the embryo begins to express its distinct genetic makeup. It provides access to the earliest genetic information of a growing embryo, making it an essential component of genetic screening. Integrating ZGA findings into PGD and PGS might open the path for a more reliable diagnosis of possible genetic abnormalities at a previously unheard-of early stage. Specific genetic diseases may be discovered via PGD before embryo implantation, enabling prospective parents to make educated choices.

Conversely, PGS looks for chromosomal abnormalities that may result in implantation failure or miscarriage. Because ZGA regulates the genetic expression these tests read, a better knowledge of ZGA may improve their predictive ability. We want to increase these approaches' dependability and predictive capacities by combining ZGA's deep knowledge, eventually giving better counsel for physicians and prospective parents. This paper phase aims to cause a paradigm change in the early identification and comprehension of genetic disorders, possibly revolutionizing reproductive care and genetic screening practices.

2.5. Evaluation of ethical implications

The interesting combination between Zygotic Genome Activation and genetic screening unavoidably leads to a complicated topography of ethical problems. Maintaining a fair balance between scientific growth and ethical responsibility is critical in this cutting-edge area of study, where possibilities are developing at an astonishing rate. One of the most important ethical issues is the idea of eugenics. Concerns regarding possible abuse arise as our ability to detect and act with genetic disorders improves. Could the abuse lead to a society where parents pick certain qualities for their future kids, resulting in a breed of 'designer babies'? It is critical to tread cautiously through these ethical waters, ensuring that the potential of genetic screening is utilized responsibly to enhance health and well-being rather than opening Pandora's box of genetic modification and prejudice. Another important ethical consideration is the complexities of informed consent. Genetic testing may provide much sensitive information about an embryo's future health and growth. Before consent, prospective parents must be thoroughly educated about the methods, potential results, and repercussions. Considering an individual's independence and right to know or not know certain facts requires careful, transparent, and compassionate communication.

Furthermore, prospective parents should consider the psychological repercussions. Knowing about possible genetic problems may be quite stressful. During these potentially difficult times, the assistance and advice provided must be of the highest standard while respecting people's emotional health and judgments. As we continue diving into the interesting world of ZGA and genetic screening, ethical issues need careful consideration and action. Future policies and regulations must be developed on a firm basis of ethical principles to ensure that scientific progress serves humanity's best interests.

2.6. Collaboration with reproductive health experts

As the paper explores further the complexities of ZGA and its consequences for genetic screening, it becomes critical to include expert perspectives from the reproductive health area. The presence of specialists in reproductive medicine and genetics adds a practical, therapeutic perspective to the largely scientific study. This partnership will increase the study's relevance and facilitate its transformation from findings in theory to real medicinal applications. Reproductive health specialists bring extensive clinical knowledge and an in-depth awareness of patient requirements. Their experience will be invaluable in evaluating and putting scientific data into a therapeutically relevant context. They will ensure that the study stays grounded in clinical practice, considering feasibility, effectiveness, patient safety, and ethical issues. Collaboration with these professionals also allows for the validation of study results. They may evaluate the results professionally, adding to the study findings' scientific legitimacy and practical relevance. It would guarantee that the study findings can directly improve clinical practices and patient care rather than just adding to academic debate.

This relationship will enable a two-way exchange of information. While the study sheds light on the function of ZGA in genetic screening, comments from reproductive health specialists will help shape future research paths, ensuring that the study remains relevant to contemporary medical concerns and patient requirements. Finally, this collaboration will help to achieve a common goal: advancing genetic screening procedures, increasing reproductive outcomes, and optimizing patient care. The technique used for this study is extensive and novel, intending to reveal the substantial consequences of ZGA in the complex realm of genetic screening. This paper aims to significantly improve reproductive health and genetics via rigorous approaches and coordinated efforts.

3. Results

3.1. Research and publication trends

We discovered 549 papers through a systematic search using the phrase “zygotic genome activation” [Title/Abstract] in the PubMed Advance search engine. There were 89 narrative and nonsystematic reviews among the 549 papers. When looking at publishing patterns, there has been a significant increase since 2014 (Fig. 1). We also reviewed the most recent research and summarized the results table for assessing paper aims, methodologies, genetic profiles, study models, and ZGA findings (Table S1, Appendix).

Fig. 1.

Trends of publication of ZGA, extracted from PubMed data on July 23, 2023.

3.2. ZGA−related gene profile

To understand gene expression regulation, it is crucial to determine the active genes at each phase of the chromatin remodeling program. Comprehensive investigations have been undertaken in the setting of widespread Zygotic Genome Activation (ZGA) employing genome-wide analytical approaches such as DNA microarrays and RNA sequencing (RNAseq).1, 2, 3 These studies have shown a rich landscape of gene function in late two-cell embryos, demonstrating the presence of almost 10,000 genes that play important functions during this developmental period. Interestingly, these genes have different profiles than those seen in oocytes. Notably, almost 3,000 genes have greater expression levels in late two-cell stage oocytes than in MII-stage oocytes.¹

While several oocyte-specific genes remain dormant throughout this stage, genes with two-cell-specific activities, such as ZO-1 (Tjp1), which is crucial for tight junction formation, are actively expressed (Fig. 2).² These results give insight into the dynamic and complex nature of gene expression regulation during chromatin remodeling, especially in the setting of ZGA.

Fig. 2.

Pathway showing the gene connection related to ZO-1 (Tjp1), forms tight junctions (Adopted from KEGG database on 25th July 2023).

The gene expression cycles of oocyte signaling genes alter significantly throughout the late two-cell stage. Notably, genes including Fzd2, Smad7, and Jag2 have increased expression, but Smad1 had decreased expression.¹ According to gene ontology studies, temporarily produced genes are predominantly linked with tasks related to the transcription process, metabolism, and the cell's life cycle during this stage.²

c-Myc has been identified as a possible master regulator during considerable Zygotic Genome Activation by gene network research.³ Furthermore, genome-wide noncoding RNA investigations have shown a broad variety of long noncoding and short RNAs synthesised during massive ZGA.⁴ Furthermore, a transposon investigation revealed substantial LINE1 production during the two-cell phase.⁵

Beyond big ZGA, genome-wide studies have discovered hundreds to thousands of genes that are transcribed during moderate ZGA. When compared to MII-stage oocytes in the one-cell or early two-cell stage, the expression levels of these genes are deemed low ZGA. The accuracy of these investigations, however, has been called into question owing to the significant quantity of maternal mRNA that lingers at these stages after fertilization, greatly exceeding that of zygotic mRNA. Furthermore, in RNA sequencing, greater RNA adenylation after fertilization utilizing poly(A)-selected RNA may generate misunderstanding between polyadenylation modifications and one-cell transcription.8, 9 As a consequence, identifying genes expressed during mild ZGA via genome-wide studies remains difficult.

Nonetheless, several genes, such as MuERV-L, have been verified as minor ZGA genes at the one-cell stage using accurate reverse-transcription PCR analysis.¹⁰ Another RNAseq investigation employing whole RNA rather than poly(A)-selected RNA discovered 23 genes that are expected to be transcribed during the one-cell stage, with expression levels 30 times greater in late one-cell embryos compared to MII-stage oocytes. Furthermore, following treatment with 5,6-dichlorobenzimidazole riboside, an RNA polymerase II activity inhibitor,¹¹ their expression dropped. Intronic sequences were found in these transcripts, indicating inadequate splicing activity at the one-cell stage.

Further research employing introns to examine mRNA levels in RNAseq data found hundreds of genes that were most likely transcribed during mild ZGA.¹¹ Surprisingly, 90 % of these genes were transcribed in the one-cell stage, despite the fact that each gene had a low level of expression.¹² Notably, the majority of oocyte-specific genes were not transcribed, but intergenic regions were broadly transcribed at low levels in one-cell-stage embryos, showing ubiquitous transcription throughout a large section of the genome.¹¹ During late two-cell stage embryos, selective expression patterns arise in contrast to the global, promiscuous expression found throughout the whole genome of one-cell stage embryos.² The profiles of transcribed genes varied dramatically throughout the one- and two-cell phases, with a correlation value of just 0.309.¹³ During the shift from one to two cells, over 4,000 genes are up- and down-regulated.¹³

3.3. In silico study

This study's dataset was obtained from a prior article.¹⁴ GO enrichment analysis was performed on genes extracted from the ZGA section using the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo). Five databases have been chosen for our investigation, and the details of the selected datasets are shown in Table 1. The information included in a dataset on rewirable networks of gene control in the preimplantation embryonic growth of two different mammalian species is shown in Fig. 3.

Table 1.

Gene Expression Omnibus database used in the paper.

GSE dataset	Organism	Sample number	Gene	PMID	Platform
GSE18290	Homo sapiens	18	ZO-1 (Tjp1)	74228260	GPL570: [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GSE21143	Mus musculus	6	Fzd2	20478531	GPL1261: [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
GSE10421	Mus musculus	30	Smad7	18539898	GPL4134: Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F
GSE8425	Mus musculus	6	Jag2	17321057	PL339: [MOE430A] Affymetrix Mouse Expression 430A Array
GSE38509	Mus musculus	24	c-Myc	24496101	GPL6246: [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array

Fig. 3.

The details of dataset about rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species.¹

The analysis of a chosen dataset using GEO2R was used for contrasting two or more sets of specimens in order to locate genes whose expression varies depending on the experimental circumstances. The findings are summarized in the form of a table that lists the genes in descending order of their level of importance (Fig. 4).

Fig. 4.

comparing two or more groups of samples in order to identify genes that are differentially expressed across experimental conditions.

A PPI network analysis was performed on the dataset to analyze protein–protein interactions (PPI). Genes were loaded into the Search Tool for Retrieval of Interacting Genes (STRING, https://www.string-db.org), and interactions with a total score higher than 0.5 were evaluated for network building. Cytoscape (version 3.7.2) was used to visualize the generated network. The cytoHubba plugin was used to identify important genes across the network, and genes were prioritized according to their level of relevancy scores using the “Betweenness” method. Hub genes are one of the 10 highest-scoring genes in our ranking (Fig. 5).

Fig. 5.

Protein–protein interaction (PPI) network analysis for selected dataset.

4. Religious consideration on ZGA

To properly comprehend the Islamic position on ethics regarding zygotic genome editing, one must first understand the larger context of genomics. Many Muslim religious thinkers and biomedical scientists have seen the study of human genes and genomes as a noble quest to deepen our knowledge of human nature throughout history. Genomic research, including genome editing, is typically viewed as an ethical practice within this positive context.²

Two precautionary principles are often used to qualify and, in some cases, restrict this wide permissibility under particular situations. The first principle is centered on respect for human dignity.³ Any study that jeopardizes the worth and dignity of human participants, such as exposing them to damaging testing without their informed permission, is considered unethical. Because of their varied understandings of human nature, Muslim religious scholars have differing viewpoints on human dignity concerning genomics and genome editing.

The second premise emphasizes the need to adhere to Islamic religious norms and the larger religio-ethical framework known as Sharia in all scientific disciplines, including genomics. Even though the study is safe and has no bodily risks, it is deemed unethical if it violates any Sharia-based values. The centrality of the marriage institution as the only way of producing a family is a frequent issue among Muslim religious scholars.⁴ As a result, children should be born solely to prospective biological parents with a true marital tie.

Beyond these broad concepts, moral judgments about genome editing are not universal and may vary greatly.⁵ The ethical concerns often revolve around two major issues: the sort of cells being transformed and the aim of the changes.

The potential advantages and hazards of somatic cell editing are restricted since the edited cells only influence the person with them. This form of genome editing raises no serious ethical problems, particularly for research or therapeutic objectives, with adequate permission and risk assessment.⁶ Individuals do not “own” their bodies in the Islamic worldview; they are entrusted to care for them as God's trustees. As a result, humans may make judgments about their bodies as long as they do not expose themselves to unnecessary or unjustified dangers, thereby disobeying the dictates of the Owner (God). Some religious experts, however, argue that innovative technologies, like genome editing, whose usefulness and safety have not been uniformly demonstrated, should be utilized in clinical settings only when conventional therapies are inadequate.

Conversely, some Muslim religious officials are concerned about germline genome editing.⁵ While they oppose changing germline cells, they argue for a careful approach, equivalent to a moratorium, when using this technology for human therapy. Because of safety and efficacy concerns, these scientists believe germline genome editing should be temporarily halted. Unlike somatic cell editing, germline cell editing affects both the person and future generations.⁷ The larger spectrum of possible impacts and long-term consequences demands more careful consideration. Nonetheless, they see no problem using this technology for study or animal testing.

Secular ethical arguments often concentrate on two fundamental difficulties associated with germline genome editing, although Muslim religious scholars pay less attention to these subjects. One example is the impossibility of getting permission from future generations impacted by germline cell editing.⁸ Muslim scholars typically believe that parental consent is adequate for such choices, citing past examples of young people being directed by their parents' decisions. However, ethical issues for germline cell alterations may vary dramatically because of the possible long-term consequences that reach beyond one's immediate progeny. The second ethical quandary is the moral standing of embryos employed in germline editing research.9, 10 The majority of Muslim religious experts are unconcerned about this problem. They have authorized the use of nonviable or excess embryos from in vitro fertilization for scientific purposes, as outlined in their courses on embryonic stem cell study and assisted reproductive technologies.

Embryos, in their opinion, do not have the moral standing of a human being until they are placed in the uterus, making them appropriate for a study that may yield significant insights.

However, Muslim religious authorities are concerned about gene therapy, which involves the transfer of reproductive cells between people.9, 10 They oppose such transfers, especially between unmarried couples, since they would destroy lineage lines. According to Islamic beliefs, conception should occur only inside marriage when both parties contribute biologically to the genetic makeup of their future child.

5. Discussion

The fundamental study delves deeply into the junction between ZGA and genetic characteristics, bioethical and religious issues, and screening, especially concerning assisted reproductive technologies such as PGD and PGS. The thorough dive into the molecular complexities of ZGA, as well as the advanced approaches used, demonstrate a research strategy that is both rigorous and comprehensive. Over the past three decades, researchers have uncovered molecular components and hypothesized processes for how the embryo transforms from transcriptionally quiet to transcriptionally competent.² Wu and Vastenhouw explored the molecular actors that define the molecular landscape of ZGA and their method of action in activating the transcription program in the developing embryo.³ In contrast, previous studies in the field tend to concentrate on either the biological elements of ZGA or the therapeutic uses of genetic screening.⁴ This study is unique and thorough due to its bifocal approach, which integrates both the molecular and clinical realms. The work provides vital insights into the possible windows for effective genetic screening, especially during the early stages of development, by recognizing the switch from maternal to embryonic control throughout embryogenesis.

Furthermore, the approach used is quite noteworthy. The combination of a thorough literature review, detailed data collecting and analysis, and an in vitro exploratory investigation highlights the breadth of the research. A multi-pronged approach like this provides a thorough knowledge of ZGA from theoretical and practical aspects. Compared to previous papers, one major quality of this study is its focus on comparing ZGA timing among species. This comparative study improves our knowledge of embryonic development and places human ZGA into a larger biological context. Other talks often need such comparisons, thus losing out on insights that may be gained from inter-species differences.

Next-generation sequencing and other modern genomic technologies distinguish this study even more.⁵ While many studies recognize the power of these methods, the hands-on approach used here, particularly in mapping the transcriptome alterations during ZGA, is admirable. This level of investigation is expected to offer complete knowledge of the process, putting the study on the leading edge of reproductive genetics. Furthermore, as mentioned in the essay, coordination with reproductive health professionals adds a crucial dimension. Bridging the gap between raw scientific data and its practical, clinical use is a common translational medicine difficulty. By collaborating with reproductive health professionals, the research assures that its results are scientifically sound and clinically useful. Such partnership increases the potential effect of the study by anchoring it in existing medical practices and patient requirements.

Incorporating ethical issues into the study framework indicates a level of forethought that could be improved in scientific inquiries. Given the delicate nature of genetic screening and its possible consequences for human lives, every thorough research in this arena must include the ethical implications. Addressing eugenics, informed consent and psychological consequences demonstrate a well-rounded and ethical study strategy. The article's study on ZGA and its involvement in genetic profiling, religious concerns, and screening is a groundbreaking investigation into a critical sector. Its strong methodology, collaborative approach, and ethical concerns place it at the forefront of reproductive genetics research. As the field evolves, this study will serve as a reference point, leading future research and changing therapeutic practices.

6. Conclusion

Zygotic Genome Activation is one of the most important stages of embryonic development. The pivotal moment in development is when the embryo begins its intrinsic genetic programming, shifting from maternal to zygotic control. The careful examination of this important process and its nuanced comprehension reveals its tremendous effect on the direction of early development, laying the groundwork for the complex organism to come.

With the rapid advancement of genomics and reproductive medicine, using ZGA in genetic screening has emerged as a critical concern. Techniques like PGD and PGS, which originally had restricted capabilities, are now on the verge of revolutionary advancements. By combining ZGA findings, these approaches have the potential to achieve exceptional precision, allowing doctors to probe deeper into embryo genetic repertoires than ever before. It may aid in the early detection of possible genetic abnormalities, even before they have the opportunity to develop. Early identification and advances in gene treatments may ultimately lead to approaches to correct or control these defects, providing prospective parents with better-informed options and improving reproductive outcomes.

However, using ZGA in genetic screening is challenging. As with many groundbreaking scientific endeavors, it is accompanied by many questions and complexity. While the procedure provides an excellent chance to learn about our genetic origins, it also raises the issue of how much interference is too much. When does our drive for knowledge and improving human health turn into playing God? The controversy over 'designer babies' is only one example of the many ethical quandaries we may face. This junction of fast scientific development and ethical problems will influence the future trajectory of ZGA and genetic screening research and applications. There is an unquestionable obligation on the part of researchers and doctors to ensure that the growth of knowledge does not come at the expense of sacrificing ethical standards. When paired with the ability to act, genetic screening can potentially change future generations' genetic destiny. The ethical components of such strong treatments, including informed consent, possible eugenics, psychological effects on parents, and social ramifications, cannot be overlooked. They need rigorous, global dialogue, necessitating cooperation among scientists, ethicists, politicians, and society.

Furthermore, as we enter this new age of embryonic genetics, information must be conveyed with clarity, compassion, and honesty. Prospective parents, who are often at the forefront of these breakthroughs, must be given thorough knowledge to empower them to make choices that are consistent with their values, beliefs, and the best interests of their future children. In hindsight, the discovery of ZGA and its implications for genetic screening represents both the wonder and the responsibility of scientific advancement. It provides a window into the complexities of our primordial genetic code, revealing truths that have long been hidden. With this increased knowledge, however, comes the responsibility to use it wisely, ensuring that it serves as a light of hope and development rather than guiding us into morally muddy seas.

At this stage, the future contains enormous potential. The symbiotic link between ZGA and genetic screening has the potential to revolutionize reproductive care. However, the legacy of these advances will be determined by our collective intelligence, ethics, and moderation. In sum, understanding ZGA and incorporating it into genetic screening is about more than simply interpreting the code of life; it is also about maintaining the sanctity and dignity of that existence.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

All data are presented in the paper.

Authors' contributions

FR, NHQ, AZ conducted the data analysis and wrote the first draft of the manuscript. FR and RK contributed to the draft review, editing, and validation. FR and NHQ, AZ participated in language editing. All authors were involved in drafting and revising the manuscript.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary material

The following are the Supplementary data to this article: