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Keywords = in vitro gametogenesis (IVG)

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31 pages, 3754 KiB  
Review
Artificial Gametogenesis and In Vitro Spermatogenesis: Emerging Strategies for the Treatment of Male Infertility
by Aris Kaltsas, Maria-Anna Kyrgiafini, Eleftheria Markou, Andreas Koumenis, Zissis Mamuris, Fotios Dimitriadis, Athanasios Zachariou, Michael Chrisofos and Nikolaos Sofikitis
Int. J. Mol. Sci. 2025, 26(15), 7383; https://doi.org/10.3390/ijms26157383 - 30 Jul 2025
Viewed by 827
Abstract
Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, [...] Read more.
Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article
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18 pages, 1258 KiB  
Review
Recent Developments in In Vitro Spermatogenesis and Future Directions
by In Ki Cho and Charles A. Easley
Reprod. Med. 2023, 4(3), 215-232; https://doi.org/10.3390/reprodmed4030020 - 11 Sep 2023
Cited by 11 | Viewed by 11619
Abstract
Recent developments in stem cell technologies have made significant advancements in the field of in vitro gametogenesis. In vitro gametogenesis (IVG) is a promising technology where functional gametes (sperm or egg cells) can be generated from stem cells. Scientists have made continuous advancements [...] Read more.
Recent developments in stem cell technologies have made significant advancements in the field of in vitro gametogenesis. In vitro gametogenesis (IVG) is a promising technology where functional gametes (sperm or egg cells) can be generated from stem cells. Scientists have made continuous advancements in the field and successfully derived fully functional sperm from stem cells in mice. Two recent papers generated excitement in IVG by generating bi-maternal and bi-paternal mice from embryonic stem cells (ESCs) and pluripotent stem cells (PSCs). IVG is a promising technology with potential applications that include infertility treatment, fertility preservation, same-sex reproduction, bypassing oocyte depletion in women with advanced age, conservation biology, genetic disorder prevention, and research into human germ cell development. In vitro spermatogenesis (IVS) is the attempt to recreate the process of spermatogenesis in a culture system. Spermatogenesis is essential for male fertility and reproductive health, but it can be impaired by various factors such as genetic defects, environmental toxicants, infections, aging, or medical therapies. Spermatogenesis is a complex and highly regulated process involving multiple cell proliferation, differentiation, and maturation stages. The main challenges of IVS are to provide a suitable microenvironment that mimics the testis in vivo, to support the survival and development of all the cell types involved in spermatogenesis, and to achieve complete and functional spermatogenesis. Therefore, there is a great interest in developing methods to study spermatogenesis in vitro, both for basic research and clinical applications. This review covers recent developments in in vitro spermatogenesis in the past two years. Advances in tissue engineering and regenerative medicine have introduced techniques like ex vivo tissue culture and technologies such as bioreactors, microfluidic systems, and organoids. Bioreactors and microfluidic systems replicate physiological conditions for tissue and cell cultivation, while organoids model organ functionality. Meanwhile, scaffolds, made from various materials, provide essential structural support, guiding the growth and organization of cells into functional tissues. Full article
(This article belongs to the Special Issue Reviews on Reproductive Biology and Medicine)
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13 pages, 631 KiB  
Review
In Vitro Gametogenesis in Oncofertility: A Review of Its Potential Use and Present-Day Challenges in Moving toward Fertility Preservation and Restoration
by Victoria G. Wesevich, Christopher Arkfeld and David B. Seifer
J. Clin. Med. 2023, 12(9), 3305; https://doi.org/10.3390/jcm12093305 - 6 May 2023
Cited by 7 | Viewed by 7095
Abstract
Current fertility preservation options are limited for cancer survivor patients who wish to have their own biological children. Human in vitro gametogenesis (IVG) has the hypothetical ability to offer a unique solution to individuals receiving treatment for cancer which subsequently shortens their reproductive [...] Read more.
Current fertility preservation options are limited for cancer survivor patients who wish to have their own biological children. Human in vitro gametogenesis (IVG) has the hypothetical ability to offer a unique solution to individuals receiving treatment for cancer which subsequently shortens their reproductive lifespan. Through a simple skin punch biopsy, a patient’s fertility could be restored via reprogramming of dermal fibroblast cells to induced pluripotent stem cells, then from primordial germ cell-like cells into viable oocytes and spermatocytes which could be used for embryogenesis. Induced pluripotent stem cells could also be used to form in vitro environments, similar to the ovary or testes, necessary for the maturation of oogonia. This would allow for the entire creation of embryos outside the body, ex vivo. While this area in stem cell biology research offers the potential to revolutionize reproduction as we know it, there are many critical barriers, both scientific and ethical, that need to be overcome to one day see this technology utilized clinically. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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19 pages, 1703 KiB  
Article
The Ethics of Genetic Cognitive Enhancement: Gene Editing or Embryo Selection?
by Marcelo de Araujo
Philosophies 2020, 5(3), 20; https://doi.org/10.3390/philosophies5030020 - 3 Sep 2020
Cited by 5 | Viewed by 21417
Abstract
Recent research with human embryos, in different parts of the world, has sparked a new debate on the ethics of genetic human enhancement. This debate, however, has mainly focused on gene-editing technologies, especially CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). Less attention has [...] Read more.
Recent research with human embryos, in different parts of the world, has sparked a new debate on the ethics of genetic human enhancement. This debate, however, has mainly focused on gene-editing technologies, especially CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). Less attention has been given to the prospect of pursuing genetic human enhancement by means of IVF (In Vitro Fertilisation) in conjunction with in vitro gametogenesis, genome-wide association studies, and embryo selection. This article examines the different ethical implications of the quest for cognitive enhancement by means of gene-editing on the one hand, and embryo selection on the other. The article focuses on the ethics of cognitive enhancement by means of embryo selection, as this technology is more likely to become commercially available before cognitive enhancement by means of gene-editing. This article argues that the philosophical debate on the ethics of enhancement should take into consideration public attitudes to research on human genomics and human enhancement technologies. The article discusses, then, some of the recent findings of the SIENNA Project, which in 2019 conducted a survey on public attitudes to human genomics and human enhancement technologies in 11 countries (France, Germany, Greece, the Netherlands, Poland, Spain, Sweden, Brazil, South Africa, South Korea, and United States). Full article
(This article belongs to the Special Issue Human Enhancement Technologies and Our Merger with Machines)
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