Frozen potential: embryo research at the crossroads of ethics, regulation and scientific opportunity.

In an era of expanding reproductive possibilities, the human embryo has come to represent both immense potential and profound constraint. Advances in medically assisted reproduction (MAR) have led to the cryopreservation of hundreds of thousands of embryos each year, yet many remain unused and are ultimately discarded. Meanwhile, studies aimed at understanding infertility, early human development and preventing miscarriage continue to face significant barriers, with only a small fraction of embryos ever donated to research.

Immune Dysregulation and Trophoblastic Dysfunction as a Potential Cause of Idiopathic Recurrent Pregnancy Loss.

Recurrent pregnancy loss (RPL) is a multifactorial condition affecting 1-5% of couples, often with unclear etiology. Idiopathic pregnancy losses (iPLs) are particularly challenging due to unknown molecular mechanisms. This study investigates the transcriptomic profiles of first-trimester products of conception (POC) from iPLs to uncover underlying molecular pathways.

Extended In Vitro Culture of Human Embryos.

Recent innovations in extended in vitro culture (IVC) systems have revolutionized our understanding of human peri-implantation development. Building on foundational animal studies, refined protocols now support human embryo culture beyond the blastocyst stage, providing unprecedented access to previously elusive developmental events. These systems have yielded critical insights into early morphogenetic processes, lineage specification, and tissue organization, significantly advancing developmental biology.

Stem cell-derived gametes: what to expect when expecting their clinical introduction.

Stem cell-derived (SCD)-gametes derived from induced or autologous (i.e. patient-specific) cells may help mitigate human fertility problems caused by physiological or social factors in the (near) future.

Building a human pluripotent stem cell-based gonadal niche: improving in vitro systems with in vivo insights.

Background: The gonadal somatic niche is crucial for sex determination and gamete formation throughout the human life cycle. However, key steps in gonadal somatic lineage differentiation occur during embryonic and foetal development, making them difficult to study in humans. In vitro differentiation models are therefore needed to investigate gonadal development, support in vitro gametogenesis, and study infertility.

Biphasic CAPA-IVM Improves Equine Oocyte Quality and Subsequent Embryo Development Without Inducing Genetic Aberrations.

In vitro maturation (IVM) of oocytes retrieved from ovum pick-up (OPU) or ovarian tissue (OT) is a standard approach for patients with specific conditions where prior hormonal stimulation is contraindicated. However, the developmental competence of oocytes matured in vitro is still inferior to that of oocytes matured in vivo. Capacitation IVM (CAPA-IVM) includes an extra step of pre-maturation culture (PMC) with c-type natriuretic peptide (CNP) as a meiotic arrestor to better synchronize cytoplasmic and nuclear maturity in oocytes by allowing the cytoplasm additional time to acquire essential components critical for optimal competency.

Characterization of somatic testicular cells during human development: fetal, peripubertal, adolescent and adult human testis from healthy and infertility related disease.

The transcription factor GATA4 is found in Sertoli and Leydig cells, whereas SOX9 is exclusive to Sertoli cells, being both factors essential for the normal development of murine and human fetal testis. In turn, the steroidogenic acute regulatory protein (STAR) is specifically expressed in Leydig cells. Nevertheless, the function of STAR, GATA4 and SOX9 in peripubertal, adolescent and adult testes in Klinefelter syndrome and azoospermic patients remains poorly understood.

An engineered tumor organoid model reveals cellular identity and signaling trajectories underlying SFPQ-TFE3 driven translocation RCC.

Translocation renal cell carcinoma (tRCC) is a rare, aggressive kidney cancer primarily occurring in children. They are genetically defined by translocations involving MiT/TFE gene family members or . The biology underlying tRCC development remains poorly understood, partly due to the lack of representative experimental models.

Human and non-human primate female in vitro gametogenesis toward meiotic entry: a systematic review.

In vitro gametogenesis offers a powerful platform to explore the complexities of female germline development while bypassing ethical and technical barriers in human and non-human primate research. This systematic review examined 23 articles that reported meiotic entry from differentiated pluripotent stem cells or ex vivo-cultured fetal germ cells from humans, cynomolgus monkeys or marmosets and were published between 2009 and 2025. By comparing methodologies and outcomes, the review highlighted current progress and ongoing challenges in inducing meiotic progression in primates.

removal of pro-fibrotic collagen and rescue of metabolic function in human ovarian fibrosis.

Tissue fibrosis, with the excessive accumulation of extracellular matrix, leads to organ dysfunction. The ovary shows signs of fibrosis from an early age, creating a permissive environment for ovarian cancer. A robust culture-platform to study human ovarian fibrosis would enable screens for antifibrotic drugs to prevent or even reverse this process.

In vitro growth of secondary follicles from cryopreserved-thawed ovarian cortex.

Study Question: Can secondary follicles be obtained from cultured cryopreserved-thawed human ovarian cortical tissue?

Summary Answer: We obtained high-quality secondary follicles from cultured cryopreserved-thawed human ovarian cortical tissue from cis female donors (cOVA), but not from trans masculine donors (tOVA) in the same culture conditions.

What Is Known Already: The in vitro growth of oocytes present in unilaminar follicles into metaphase II stage (MII) oocytes has been previously achieved starting from freshly obtained ovarian cortical tissue from adult cis female donors. This involved a multi-step culture protocol and the first step included the transition from unilaminar follicles to multilayered secondary follicles.

Ethical considerations on the moral status of the embryo and embryo-like structures†.

The current article provides an ethical reflection on the moral status of the human embryo, which is a crucial factor in determining permissible actions involving embryos and the extent of their protection. It advocates for the extension of the research period for embryos to 28-days post fertilization. It also states that integrated embryo-like structures (ELSs) should not currently be given the same moral status as natural embryos.

Human Ovarian Surface Epithelium Organoids as a Platform to Study Tissue Regeneration.

The ovarian surface epithelium (OSE), the outermost layer of the ovary, undergoes rupture during each ovulation and plays a crucial role in ovarian wound healing while restoring ovarian integrity. Additionally, the OSE may serve as the source of epithelial ovarian cancers. Although the OSE regenerative properties have been well studied in mice, understanding the precise mechanism of tissue repair in the human ovary remains hampered by limited access to human ovaries and suitable in vitro culture protocols.

Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth.

Mechanisms underlying human hepatocyte growth in development and regeneration are incompletely understood. In vitro, human fetal hepatocytes (FH) can be robustly grown as organoids, while adult primary human hepatocyte (PHH) organoids remain difficult to expand, suggesting different growth requirements between fetal and adult hepatocytes. Here, we characterize hepatocyte organoid outgrowth using temporal transcriptomic and phenotypic approaches.

Binucleated human hepatocytes arise through late cytokinetic regression during endomitosis M phase.

Binucleated polyploid cells are common in many animal tissues, where they arise by endomitosis, a non-canonical cell cycle in which cells enter M phase but do not undergo cytokinesis. Different steps of cytokinesis have been shown to be inhibited during endomitosis M phase in rodents, but it is currently unknown how human cells undergo endomitosis. In this study, we use fetal-derived human hepatocyte organoids (Hep-Orgs) to investigate how human hepatocytes initiate and execute endomitosis.

One-third of amenorrheic transmasculine people on testosterone ovulate.

Transmasculine people usually reach amenorrhea within 6 months of adequate testosterone treatment. It is often assumed that no ovulation occurs during amenorrhea. However, in this study, we report recent ovulatory activity in amenorrheic transmasculine people on testosterone therapy at gender-affirming oophorectomy.

Isolation and In Vitro Culture of Germ Cells and Sertoli Cells from Human Fetal Testis.

In the human fetal testis, fetal germ cells (FGCs) are progressively surrounded by supporting Sertoli cells inside seminiferous cords. During the second trimester, the FGCs develop asynchronously and can be observed in several stages of development. However, the mechanism that regulates the transition between the different developmental stages as well as the formation of spermatogonia is currently not well understood.

Characterization of the human fetal gonad and reproductive tract by single-cell transcriptomics.

During human fetal development, sex differentiation occurs not only in the gonads but also in the adjacent developing reproductive tract. However, while the cellular composition of male and female human fetal gonads is well described, that of the adjacent developing reproductive tract remains poorly characterized. Here, we performed single-cell transcriptomics on male and female human fetal gonads together with the adjacent developing reproductive tract from first and second trimesters, highlighting the morphological and molecular changes during sex differentiation.

Human fetal brain self-organizes into long-term expanding organoids.

Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization.

Modelling post-implantation human development to yolk sac blood emergence.

Implantation of the human embryo begins a critical developmental stage that comprises profound events including axis formation, gastrulation and the emergence of haematopoietic system. Our mechanistic knowledge of this window of human life remains limited due to restricted access to in vivo samples for both technical and ethical reasons. Stem cell models of human embryo have emerged to help unlock the mysteries of this stage.

Classification of Atretic Small Antral Follicles in the Human Ovary.

The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition.

Cell-cell interactions during the formation of primordial follicles in humans.

Gametogenesis is a complex and sex-specific multistep process during which the gonadal somatic niche plays an essential regulatory role. One of the most crucial steps during human female gametogenesis is the formation of primordial follicles, the functional unit of the ovary that constitutes the pool of follicles available at birth during the entire reproductive life. However, the relation between human fetal germ cells (hFGCs) and gonadal somatic cells during the formation of the primordial follicles remains largely unexplored.

Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures.

Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite-hepatocyte interaction is inadequate due to limitations of existing in vitro models. We explore the suitability of hepatocyte organoids (HepOrgs) for Pf-development and show that these cells permitted parasite invasion, differentiation and maturation of different Pf strains.