Systems Biology in Reproductive Medicine最新文献

{"title":"<i>ACE</i> gene and male infertility: a South Slavic case-control study and multi-omics data integration.","authors":"Tanja Kunej, Rebeka Podgrajsek, Helena Jaklic, Alenka Hodzic, Martin Stimpfel, Olivera Miljanovic, Momcilo Ristanovic, Ivana Novakovic, Dijana Plaseska-Karanfilska, Predrag Noveski, Sasa Ostojic, Alena Buretic-Tomljanovic, Antun Grskovic, Borut Peterlin","doi":"10.1080/19396368.2025.2566747","DOIUrl":"https://doi.org/10.1080/19396368.2025.2566747","url":null,"abstract":"<p><p>Components of the renin-angiotensin system (RAS) are expressed in both female and male reproductive tracts, with angiotensin I converting enzyme (ACE) being an important component for male reproductive function, as shown in animal models. The most studied <i>ACE</i> polymorphism is the Alu insertion-deletion (I/D), which has been proposed to have a negative effect on male fertility. Given the conflicting evidence in the literature, we conducted a multicentric case-control study to investigate the association between the <i>ACE</i> Alu I/D polymorphism and impaired spermatogenesis. Using PCR amplification and agarose electrophoresis, we genotyped the <i>ACE</i> gene Alu I/D polymorphism in 745 South Slavic men. The study group consisted of 457 patients with impaired spermatogenesis, 239 with non-obstructive azoospermia (NOA) and 218 with oligoasthenoteratozoospermia (OAT) and a control group of 288 fertile men. No association was found between the Alu I/D polymorphism and these semen phenotypes, suggesting that it is not associated with NOA or severe OAT in this cohort. To provide a broader regulatory context, we also developed an integrative atlas of <i>ACE</i> regulatory elements by in silico multi-omics analysis using genomics databases and bioinformatics tools. Data integration revealed various regulatory mechanisms at multiple omics levels, including genomics, epigenomics, miRNAomics, transcriptomics, proteomics and epiproteomics. These include genomic variants with predicted deleterious effects, a CpG island, microRNAs (miRNAs) and post-translational modifications (PTMs). In addition, protein interaction analysis revealed that ACE is indirectly linked to several proteins previously associated with male infertility and is also targeted by miRNA previously associated with oligozoospermia. This comprehensive, multi-faceted approach, combining genetic association analysis with bioinformatics, provides insights into <i>ACE</i> regulation in its broader molecular context. These results emphasize the importance of further integrative multi-omics and systems biology research to better understand the role of ACE in male reproductive function.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"524-537"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viruses and assisted reproductive technologies (ART).","authors":"Marina Leiva, Maria Lopez-Panades, Di Wang, Mar Domingo-Lopez, Judit Castillo, Ignasi Roig, Rafael Oliva, Meritxell Jodar","doi":"10.1080/19396368.2025.2531744","DOIUrl":"https://doi.org/10.1080/19396368.2025.2531744","url":null,"abstract":"<p><p>This comprehensive review reflects our current knowledge of viral infections in the context of assisted reproduction, highlighting the latest research and guidelines. It focuses on the major viral pathogens that have a significant impact on human reproduction. It examines their impact on both male and female reproductive systems, fertility outcomes, and pregnancy, with a particular emphasis on managing the risks of transmission in assisted reproductive technologies (ART). State-of-the-art screening protocols and preventive measures are outlined, highlighting the progress made in minimizing viral transmission and ensuring safe reproductive outcomes. By presenting the current landscape of viral management in reproductive health, this review underscores the need for continued vigilance, research, and innovation to face viral threats.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"246-278"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ovarian stimulation protocols in fresh cycles and in elective freeze-all cycles.","authors":"Ioannis E Messinis, Christina I Messini, George Anifandis","doi":"10.1080/19396368.2025.2540280","DOIUrl":"https://doi.org/10.1080/19396368.2025.2540280","url":null,"abstract":"<p><p>Ovarian stimulation is applied to women undergoing IVF treatment with the aim of selecting more than one follicle. Until a few years ago, fresh embryo transfer was the norm, but not without the risk of ovarian hyperstimulation syndrome (OHSS). In recent years, vitrification has allowed the successful freezing of all oocytes or embryos, thus favoring multiple embryo transfer in subsequent thawing cycles and eliminating the risk of OHSS. Certainly, excess embryos from fresh embryo transfer cycles can be also frozen and thawed in future transfers. In terms of the number of oocytes needed, research in recent years has shown differences between fresh embryo transfer cycles and elective freezing of all embryos, termed elective freeze-all cycles, with the fresh cycle requiring an optimal number to avoid OHSS, while in elective freeze-all cycles there appear to be no specific upper limit. Consequently, the approach to ovarian stimulation may also differ between the two types of cycles. Although GnRH antagonists are used in both cycles, in elective freezing cycles progestins tend to replace antagonists in preventing the endogenous LH surge. However, it is unclear whether prevention of the LH surge is required in such cycles, since luteinization affecting the endometrium is not clinically relevant, as no embryo transfer occurs. This narrative review describes the current experience in ovarian stimulation for IVF, highlighting the differences between fresh and elective freeze-all cycles and the potentially different approach.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"307-329"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early embryo development: the current perspective in molecular evaluation and clinical status.","authors":"Sevastiani Antonouli, Dimitrios Ioannou, Valentina Di Nisio, Christina Messini, Georgia Kokkali, Katerina Chatzimeletiou, Peter Sutovsky, Alexandos Daponte, George Anifandis","doi":"10.1080/19396368.2025.2551009","DOIUrl":"https://doi.org/10.1080/19396368.2025.2551009","url":null,"abstract":"<p><p>Early embryo development and competence mechanisms are paramount to ART's success but are still underexplored in human-relevant animal models. Clinical embryo evaluation remains largely based on subjectively evaluated morphological characteristics. In the current era of biomarkers and low-input high-throughput technologies, it is possible to investigate the multi-complex molecular landscape of the embryo during development from the zygote up to the blastocyst stage. The scope of this article is to review the underlying molecular mechanisms of pre-implantation embryo development. In addition, we briefly explore the latest advances in embryo quality assessment - including molecular and epigenetic evaluation and technical advances such as time-lapse imaging and artificial intelligence - together with clinical challenges for selecting the best embryo for single embryo transfer.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"356-370"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring ovarian aging: unraveling the link between mitochondria status and oocyte as a determinant of gamete quality.","authors":"Manuel Belli, Marta Gatti, Luigi Sansone, Matteo Antonio Russo, Maria Grazia Palmerini, Stefania Annarita Nottola, Mohammad Ali Khalili, Guido Macchiarelli","doi":"10.1080/19396368.2025.2562633","DOIUrl":"10.1080/19396368.2025.2562633","url":null,"abstract":"<p><p>The variation in reproductive age among individuals is significant, with many cases of infertility involving premature ovarian aging. This issue, combined with the societal trend of delaying childbearing, leads to age-related ovarian dysfunction. Ovarian aging is related to a decline of ovarian reserve, as oocyte quantity, quality, and precocious senescence, and may affect fertility and the overall individual well-being. Mitochondria play a central role in the maintenance of any cell health. Then mitochondrial dysfunctions may be responsible also for a negative impact on the quality, number, and function of oocytes, leading to different age-related reproductive disorders, impaired oogenesis, and embryogenesis. Although a large number of researches have shown clearly that mitochondrial dysfunction and morphology changes affect the maintenance and function of all major organs and tissues, such as the brain, heart, skeletal muscle, liver, and others the mechanisms contributing to early ovarian aging, a decrease of oocyte quality, and infertility remain unclear. In this review, we summarize the role of mitochondrial dysfunction in ovarian aging, presenting recent findings on morpho-functional changes in these organelles, and highlighting how their dysfunction accelerates ovary and cell senescence. We also explore their impact on oocyte functions. The reported data highlight the critical role of mitochondria in maintaining and enhancing oocyte quality, indicating that future studies should further focus on the mechanisms underlying mitochondrial damage and on identifying mitochondrial targets that may offer promising strategies to preserve, recover, and extend fertility in aging women.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"461-484"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel homozygous missense variants in <i>SUN5</i> and <i>DNAH10</i> associated with male infertility and oligoasthenoteratozoospermia.","authors":"Qi Fang, Lanxi Ran, Xinying Bi, Song Liu, Jing Wang, Tengyan Li, Jianyong Di, Ye Liu, Fengqin Xu, Binbin Wang","doi":"10.1080/19396368.2025.2500591","DOIUrl":"10.1080/19396368.2025.2500591","url":null,"abstract":"<p><p>Genetic variants are known causes of male infertility and oligoasthenoteratozoospermia (OAT), as shown by knockout mouse models and patients with infertility. However, most OAT cases lack a definitive genetic diagnosis. Peripheral blood and semen samples were collected from a patient with OAT. Semen analysis, Papanicolaou staining, transmission electron microscopy, whole-exome sequencing (WES), Sanger sequencing, and <i>in silico</i> analyses, such as conservative analysis and conformational analyses, were used to investigate the genetic causes of OAT. Semen analysis revealed a notable reduction in sperm count and motility, and defects in sperm morphology. Light and electron microscopy showed numerous defects in the head-to-tail coupling apparatus of the sperm, and a small number of structural defects in the sperm flagella. WES identified two novel homozygous missense variants <i>SUN5</i>: c.G703A/p.A235T and <i>DNAH10</i>: c.A1436G/p.Q479R. The p.A235T and p.Q479R variants were predicted to generate aberrant SUN5 and DNAH10 proteins using <i>in silico</i> analysis. Here, we report the identification of two novel deleterious variants of <i>SUN5</i> and <i>DNAH10</i> associated with OAT, expanding the mutant spectrum of male infertility.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"190-195"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of testis proteome alterations associated with male infertility in <i>Dcaf17</i>-deficient mice.","authors":"Bhavesh Mistry, Ayodele Alaiya, Raed Abu-Dawud, Nadya Alyacoub, Dilek Colak, Mohamed Rajab, Maha Alanazi, Zakia Shinwari, Hala Ahmed, Thuraya Alharbi, Junaid Kashir, Falah Almohanna, Abdullah Assiri","doi":"10.1080/19396368.2025.2504459","DOIUrl":"https://doi.org/10.1080/19396368.2025.2504459","url":null,"abstract":"<p><p>Disruption of <i>Dcaf17</i> in mice resulted in male infertility with severe spermatogenesis defects. To investigate the molecular basis of infertility phenotype, we examined testicular proteomes of wild-type (WT) and <i>Dcaf17^-/-</i> mice using a mass spectrometry-based approach. We identified 727 and 525 differentially expressed proteins (DEPs) in 3- and 8-week old testes of <i>Dcaf17^-/-</i> mice, respectively, with an adjusted p-value cut-off of ≤ 0.05. Among these, 299 and 298 DEPs had fold change of ≥ 1.5 between WT and <i>Dcaf17^-/-</i> testes at -3- and 8-week old, respectively. In the 3-week old <i>Dcaf17^-/-</i> testes, 59.5% of the DEPs were up-regulated, while 40.5% were down-regulated. Similarly, in the 8-week old <i>Dcaf17^-/-</i> testes, 83.9% and 16.1% DEPs were up-regulated and down-regulated, respectively. Functional annotation and network analyses highlighted that many DEPs were associated with key biological processes, including ubiquitination, RNA processing, translation, protein folding, protein stabilization, metabolic processes, oxidation-reduction processes and sper-matogenesis. Subsequent immunohistochemistry and immunoblotting analyses showed higher ubiquitin levels in <i>Dcaf17^-/-</i> testes compared to WT, suggesting potential impairment in ubiquitin proteasome system (UPS) due to DCAF17 loss of function. Our data provide a basis for further work to elucidate the molecular function(s) of DCAF17 in spermatogenesis and male fertility.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"206-228"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SBiRM: future innovation and practice in Personalized and Precision Reproductive Medicine.","authors":"Stephen A Krawetz, B Charlotte","doi":"10.1080/19396368.2024.2447691","DOIUrl":"https://doi.org/10.1080/19396368.2024.2447691","url":null,"abstract":"","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of the brain-placental axis, and its relevance to the health and disease of the offspring.","authors":"Susanta K Behura","doi":"10.1080/19396368.2025.2567543","DOIUrl":"https://doi.org/10.1080/19396368.2025.2567543","url":null,"abstract":"<p><p>The placenta develops as a transient organ during pregnancy to nurture the growing fetus. It supplies nutrients and oxygen to the fetus, collects fetal waste, and safeguards the fetus from infections and adverse pregnancy conditions. Emerging evidence suggests that the placenta plays adaptive functions to protect the developing brain from injury in adverse maternal conditions. Inadequate placental support can impact the developmental process of the brain, which increases the risk of brain diseases among the offspring. There is a remarkable coordination in gene expression between the placenta and fetal brain of mice, suggesting a robust regulation of the brain-placental axis. The deregulation of the brain-placental axis can have adverse effects on the fetal programming of brain development. Defective neuronal development of the fetus due to the abnormal or non-optimal placental functions can lead to an increased risk of different neuropsychiatric diseases in the adult life of the offspring. Thus, there is a growing interest to understand placental influences on fetal brain development and its links to the risk of brain diseases. Research on the brain-placental axis, also referred to as neuroplacentology, is a rapidly emerging interdisciplinary field that integrates concepts and tools from diverse areas, including reproductive biology, neuroscience, epigenetics, systems biology, and data sciences, among others. Recently, large-scale multiomics data and systems biology approaches have been applied to investigate the functional links between the placenta and fetal brain, and to dissect the cellular and molecular mechanisms of the regulation of the brain-placental axis. The primary objective of this review is to outline the current status and the future avenues of this emerging research field that holds huge potential to advance our knowledge about the role of the placenta in the developmental origin of brain health and disease.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"504-523"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic accuracy of plasma microRNA as a potential biomarker for detection of endometriosis.","authors":"Seyed Danial Mohammadi, Ashraf Moeini, Tayebeh Rastegar, Fardin Amidi, Mojtaba Saffari, Shahrzad Zhaeentan, Setareh Akhavan, Behnaz Moradi, Faezeh Heydarikhah, Nasrin Takzare","doi":"10.1080/19396368.2025.2465268","DOIUrl":"10.1080/19396368.2025.2465268","url":null,"abstract":"<p><p>Endometriosis is a complex condition with a wide range of clinical manifestations, presenting significant challenges, particularly for young women. Its diverse and often perplexing presentations pose difficulties within the medical community. Laparoscopy remains the gold-standard diagnostic tool for endometriosis. However, alternative diagnostic methods are valuable for monitoring disease progression, assessing the likelihood of recurrence, reducing the need for surgical procedures, and facilitating timely decisions regarding fertility concerns. Recent research highlights the potential of microRNAs (miRNAs) as an alternative diagnostic test for endometriosis. A case-control study was conducted at the infertility unit of Arash Women's Hospital, involving 50 female participants, 25 with endometriosis and 25 without it. Plasma samples were collected and analyzed for the expression levels of 16 miRNAs using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Diagnostic accuracy measures were evaluated to establish a reliable and comparable diagnostic framework. Compared to the control group, downregulation of 11 miRNAs and upregulation of 5 miRNAs were observed in the case group. Regarding expression patterns, evidence from this study indicates that half of the evaluated miRNAs fall into the high-agreement category with similar studies. Sensitivity (SN) of the evaluated miRNAs ranged from 64.0% to 88.0%, while specificity (SP) ranged from 56.0% to 88.0%. The area under the curve (AUC) was reported between 0.619 (miR-135a) and 0.846 (miR-340). These findings suggest that the evaluated miRNAs demonstrate moderate to acceptable diagnostic accuracy for endometriosis.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"71 1","pages":"61-75"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}