bims-cebooc 2025-07-06 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2025–07–06
eighteen papers selected by
Gabriele Zaffagnini, Universität zu Köln

Generation of germinal-vesicle oocytes from mouse embryonic stem cells under an ovarian soma-free condition.
Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos.
Spindle morphology changes between meiosis and mitosis driven by CK2 regulation of the Ran pathway.
Nucleosome organization of mouse embryos during pre-implantation development.
Sex-converted testis soma acquires female-specific behaviors and alters XY germline identity.
Trailer Hitch coordinates P-body organization and facilitates transcript-specific mRNA regulation through nuclear actin-mediated feedback loop.
Caspar modulates primordial germ cell fate both in Oskar-dependent and Oskar-independent manner.
Single-cell long-read Hi-C, scNanoHi-C2, details 3D genome reorganization in embryonic-stage germ cells.
Visualizing developmental dynamics of nuclear morphology and transport machinery in Drosophila.
Deciphering the role of cis-regulatory elements and TFAP2C in the activation of zygotic Sox2 expression in mouse preimplantation embryos.
Hybrid incompatibility emerges at the one-cell stage in interspecies Caenorhabditis embryos.
Cohesin variants and meiotic timing shape chromosome segregation accuracy.
A comprehensive review of histone modifications during mammalian oogenesis and early embryo development.
An ex vivo uterine system captures implantation, embryogenesis, and trophoblast invasion via maternal-embryonic signaling.
RNA binding protein HuR regulated by OIP5-AS1 may be involved in maternal transcript degradation during the human maternal-to-zygotic transition.
Mediators of maternal intergenerational epigenetic inheritance in mammals.
On Modeling Ovarian Aging and Menopause Timing.
Role of mitochondrial dynamics in mouse preimplantation embryonic development and its molecular mechanisms.

Dev Cell. 2025 Jun 27. pii: S1534-5807(25)00363-6. [Epub ahead of print]

Generation of germinal-vesicle oocytes from mouse embryonic stem cells under an ovarian soma-free condition.

Yoshiaki Nosaka, Masahiro Nagano, Yukihiro Yabuta, Baku Nakakita, So I Nagaoka, Ikuhiro Okamoto, Hiromichi Sasada, Ken Mizuta, Fumiya Umemura, Hiroto Kuma, Yasushi Okochi, Yoshitaka Katou, Bernard de Massy, Azusa Inoue, Akihito Horie, Masaki Mandai, Hiroshi Ohta, Mitinori Saitou.

  In vitro oogenesis provides a platform to elucidate the mechanisms of oocyte development and advance reproductive medicine. The prevalent in vitro oogenesis model requires ovarian somatic cells (OSCs) to support oocyte development; yet, complex three-dimensional oocyte-OSC interactions pose difficulties in systems regulation and mechanistic understanding. Here, we present an OSC-free system of in vitro oogenesis: upon optimized provision of retinoic acid and bone morphogenetic protein on feeders, mouse primordial germ-cell-like cells induced from embryonic stem cells propagate robustly, and enter/progress through meiotic prophase I, generating abundant fetal oocyte-like cells at diplotene arrest. With key cytokines, signaling activators, and antioxidants, they show prominent growth and differentiate into cells comparable to germinal-vesicle oocytes in morphology, transcriptome, and histone modification profiles, with competence to resume meiosis with germinal-vesicle breakdown. By reconstituting major phases of oogenesis with minimal components, our study creates a foundation for OSC-free in vitro oogenesis in mammals, including humans.

Keywords:  epigenetic programming; in vitro oogenesis; meiosis; mouse pluripotent stem cells; oocyte development; oocyte-like cells; ovarian soma-free; primordial germ cell-like cells

DOI:  https://doi.org/10.1016/j.devcel.2025.06.008
Nat Commun. 2025 Jul 01. 16(1): 5630

Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos.

Yong-Feng Wang, Yu-Ting Wan, Qian-Rong Qi, Qing Tian, Xin-Mei Liu, Qing-Zhen Xie, Ying Yin, Li-Quan Zhou.

Histone crotonylation, a conserved post-translational histone modification, plays a crucial role in transcriptional regulation. However, its function in early embryonic development remains largely unexplored. Here, we perform genome-wide mapping of histone crotonylation in mouse and human early embryos. Our analysis reveals that histone crotonylation is highly enriched at promoter regions and exhibits distinct dynamic patterns throughout embryogenesis. Notably, strong histone crotonylation signals are observed at the mouse 2-cell and human 4-to-8-cell stages, coinciding with zygotic genome activation. In mice, Echs1 knockdown in oocytes, which suppresses histone crotonylation, results in developmental arrest at the 2-cell stage. Further investigation demonstrates that reduced histone crotonylation impairs transcriptional activity at zygotic genome activation genes, retrotransposon elements, and ribosomal DNA loci. Moreover, early embryos from aged female mice exhibit significantly diminished histone crotonylation, while supplementation with exogenous sodium crotonate enhances blastocyst formation. Collectively, our findings establish histone crotonylation as a key regulatory mechanism in early mammalian embryogenesis by facilitating transcriptional activation of zygotic genome activation genes and repetitive elements.

DOI: https://doi.org/10.1038/s41467-025-60565-z
J Cell Biol. 2025 Aug 04. pii: e202407154. [Epub ahead of print]224(8):

Spindle morphology changes between meiosis and mitosis driven by CK2 regulation of the Ran pathway.

Helena Cantwell, Hieu Nguyen, Arminja N Kettenbach, Rebecca Heald.

The transition from meiotic divisions in the oocyte to embryonic mitoses is a critical step in animal development. Despite negligible changes to cell size and shape, following fertilization the small, barrel-shaped meiotic spindle is replaced by a large zygotic spindle that nucleates abundant astral microtubules at spindle poles. To probe underlying mechanisms, we applied a drug treatment approach using Ciona eggs and found that inhibition of casein kinase 2 (CK2) caused a shift from meiotic to mitotic-like spindle morphology with nucleation of robust astral microtubules, an effect reproduced in Xenopus egg cytoplasmic extracts. In both species, CK2 activity decreased at fertilization. Phosphoproteomic differences between Xenopus meiotic and mitotic extracts that also accompanied CK2 inhibition pointed to RanGTP-regulated factors as potential targets. Interfering with RanGTP-driven microtubule formation suppressed astral microtubule growth caused by CK2 inhibition. These data support a model in which CK2 activity attenuation at fertilization leads to activation of RanGTP-regulated microtubule effectors, inducing mitotic spindle morphology.

DOI: https://doi.org/10.1083/jcb.202407154
Sci Rep. 2025 Jul 01. 15(1): 21894

Nucleosome organization of mouse embryos during pre-implantation development.

Jitao Zeng, Xiaojuan Tu, Siming Qu, Xichan Chen, Ying Wang, Xiaona Liu, Enchuan Kang, Yi Tian, Qianming Xiang, Binbin Lai, Weiwu Gao, Bing Ni, Wei He.

  Sexual reproduction begins with sperm-oocyte fusion to form a zygote, where chromatin undergoes dramatic reorganization to establish totipotency. Although nucleosomes- the basic units of eukaryotic chromatin and key epigenetic regulators- are extensively remodeled during early embryogenesis, their dynamic repositioning mechanisms and biological implications remain unclear. Here, we employed single-cell MNase sequencing (scMNase-seq) to map genome-wide nucleosome positioning and chromatin accessibility in individual mammalian embryos. We found that nucleosome positioning mirrored somatic cell patterns until the 4-cell stage, with nucleosome depletion and phasing at CTCF sites not fully established until morula formation. By integrating H3K4me3 localization and transcriptomic data, we revealed that nucleosome sparsity at transcription start sites (TSS) and flanking regions correlated with expression levels of genes critical for preimplantation development. Notably, these nucleosome-depleted regions likely serve as regulatory hubs influencing histone modification dynamics. Our study systematically delineates nucleosome reorganization principles during mammalian embryogenesis and provides a high-resolution resource for understanding chromatin remodeling in early development.

Keywords:  Chromatin organization; Embryos; H3K4me3; Nucleosome position; scMNase-seq

DOI:  https://doi.org/10.1038/s41598-025-05642-5
Development. 2025 Jul 02. pii: dev.204785. [Epub ahead of print]

Sex-converted testis soma acquires female-specific behaviors and alters XY germline identity.

Tiffany V Roach, Sneh Harsh, Rajiv Sainath, Erika A Bach, Kari F Lenhart.

  Establishment and maintenance of cellular sex identity is essential for reproduction. Sex identity of somatic and germline cells must correspond for sperm or oocytes to be produced, with mismatched identity causing infertility in all organisms from flies to humans. In adult Drosophila testes, Chronologically inappropriate morphogenesis (Chinmo) is required for maintenance of male somatic identity. Loss of chinmo leads to feminization of the male soma, including adoption of female-specific cell morphologies and gene expression. However, the degree to which feminized somatic cells engage female-specific cellular behaviors or influence the associated XY germline is unknown. Using extended live imaging, we find that chinmo-depleted somatic cells acquire cell behaviors characteristic of ovarian follicle cells, including incomplete cytokinesis and rotational migration. Importantly, migration in both contexts require the basement membrane protein Perlecan and adhesion protein E-cadherin. Finally, we find that sex- converted soma non-autonomously induce expression of an early oocyte specification protein in XY germ cells. Taken together, our work reveals a dramatic transformation of somatic cell behavior during sex conversion and provides a powerful model to study soma-derived induction of oocyte identity.

Keywords:  Chinmo; Germline; Sex-determination; Somatic cell

DOI:  https://doi.org/10.1242/dev.204785
bioRxiv. 2025 Jun 20. pii: 2025.06.18.660414. [Epub ahead of print]

Trailer Hitch coordinates P-body organization and facilitates transcript-specific mRNA regulation through nuclear actin-mediated feedback loop.

Samantha N Milano, Livia V Bayer, Julie J Ko, Gwendolyn S Posner, Caroline E Casella, Diana P Bratu.

Processing bodies (P-bodies) are dynamic, membraneless organelles that mediate mRNA storage, translational repression, and decay. While the roles of individual P-body proteins in transcript recruitment are well characterized, how the emergent biophysical properties of P-bodies contribute to selective mRNA regulation remains poorly understood. Here, we identify the RNA-binding protein Trailer Hitch (Tral) as a key regulator of P-body composition and physical state during Drosophila melanogaster oogenesis. Loss of Tral disrupts P-body structure, leading to elevated levels of Cup and reduced levels of Me31B. This compositional shift is driven by degradation of twinstar mRNA, which encodes an actin regulator, resulting in reduced nuclear actin levels and altered transcription of P-body components. Using super-resolution microscopy, RNAi-mediated knockdowns, and chemical treatments, we show that Tral is also essential for transcript-specific mRNA partitioning into P-bodies. We find that in Tral-depleted egg chambers, twinstar mRNA exhibits reduced and mislocalized P-body association, bicoid mRNA dissociates from P-bodies and is degraded, and nanos mRNA remains stably localized. This suggests that selective mRNA retention within P-bodies is governed by a network of molecular interactions, including electrostatic forces, hydrophobic contacts, and direct protein:RNA binding, which are tuned by Tral. Together, our findings position Tral as a central coordinator of P-body autoregulation, integrating transcript stability, nuclear actin dynamics, and condensate organization to govern selective mRNA partitioning.

DOI: https://doi.org/10.1101/2025.06.18.660414
Biol Open. 2025 Jul 04. pii: bio.062119. [Epub ahead of print]

Caspar modulates primordial germ cell fate both in Oskar-dependent and Oskar-independent manner.

Subhradip Das, Adheena Elsa Roy, Kanika K, Girish Deshpande, Girish S Ratnaparkhi.

  Primordial Germ Cell (PGC) formation and specification is a fundamental conserved process as PGCs are the progenitors of germline stem cells (GSCs). In Drosophila melanogaster, maternally deposited Oskar (Osk) and centrosome dynamics are two independent determinants of PGC fate. Caspar, Drosophila homolog of Fas-associated factor 1 (FAF1), promotes PGC formation/specification and maintains the PGC count by modulating both the Osk levels and centrosome function. Consistently, casplof PGCs display reduction and inefficient release/ transmission of germ plasm. Defective centrosome migration and behavior are evident even prior to PGC formation engineered by Osk and its targets. Taken together with the inability of Osk to regulate nuclear and centrosome migration, our data demonstrate that Casp encodes a novel bi-modal regulator of PGC fate as it controls Osk levels likely by downregulating translational repressor, Smaug (Smg) and also influences nuclear/centrosome migration during early mitotic nuclear division cycles (NCs 6-9) which are Osk-independent. We discuss dual functionality of Casp vis-à-vis germline/soma segregation as it helps acquire both the PGCs and the surrounding soma their individual identities.

Keywords:  Centrosome; Germplasm; Migration; Oskar; PGC; Pole Cells

DOI:  https://doi.org/10.1242/bio.062119
Nat Struct Mol Biol. 2025 Jul 04.

Single-cell long-read Hi-C, scNanoHi-C2, details 3D genome reorganization in embryonic-stage germ cells.

Jiansen Lu, Wen Li, Fuchou Tang.

During mouse development, embryonic-stage germ cells (EGCs) make crucial fate decisions, with female EGCs embarking on meiosis whereas male EGCs enter mitotic arrest until birth. Despite increasing understanding of the reprogramming of epigenetic modifications, the dynamics of three-dimensional (3D) genome structures within individual EGCs remains elusive. Here we present a single-cell input, long-read Hi-C method, termed scNanoHi-C2. We use scNanoHi-C2 to systematically dissect the dynamics of EGC chromatin structures. We find that, despite changes in autosomes similar to spermatogenesis, the X chromosomes of female EGCs show enhanced specific interactions between B compartments. By reconstructing 3D genome models, we observe dynamic chromosome positioning during meiosis, showing that the neighborhood between nonhomologous chromosomes of EGCs is relatively random. Simultaneously, transposable elements undergo dramatic chromatin reorganization and display an asymmetric distribution of Alu/B2 elements around meiotic topologically associated domain boundaries. Moreover, we find that high-order interactions in EGCs at the mitosis stage are mainly enriched in the B compartment, whereas, after the mitosis-to-meiosis transition, enriched high-order interactions shift to refined A compartments, to potentially promote meiotic-specific transcription programs during global genomic condensation. We also reveal an unexpected chromatin structure in mitotic-arrested male EGCs distinct from the previously assumed G0 status, which may prime the unique genome structure for subsequent spermatogenesis. Altogether, our study highlights the potential of scNanoHi-C2 and reveals key features of the chromatin structure reprogramming in EGCs.

DOI: https://doi.org/10.1038/s41594-025-01604-7
Dev Biol. 2025 Jul 02. pii: S0012-1606(25)00186-1. [Epub ahead of print]

Visualizing developmental dynamics of nuclear morphology and transport machinery in Drosophila.

Yuki Shindo, Shruthi Balachandra, Amanda A Amodeo.

  Communication between the cytoplasm and the nucleus requires a continuous exchange of molecules across the nuclear envelope (NE). The nuclear pore complex (NPC) is the gateway embedded in the NE through which cargo moves, while transport receptors mediate the passage of macromolecules through the NPC. Although their essential role as the components of the nuclear transport machinery has been extensively studied, how these factors respond to developmental and environmental cues has been underexplored. Here we tag the nucleoporin Nup96 and the transport receptor Impβ with mEGFP and mScarlet-I at their endogenous loci in Drosophila. We demonstrate the functionality of these markers in multiple tissues and offer new options for better visualization of nuclear morphology in densely packed, complex tissues. Then, we characterize the spatiotemporal dynamics of these markers in multiple developmental contexts. We find that Nup96 and Impβ form cytoplasmic puncta, whose size, numbers, and co-localization patterns change dynamically during oogenesis and early embryogenesis. Moreover, we find that the abundance of NPCs per nucleus decreases during early embryogenesis, complementing the emerging model in which NPCs play a regulatory role in development. The tools and observations described here will be useful in understanding the dynamic regulation of nuclear morphology and transport machinery in development.

Keywords:  Drosophila; cytoplasmic puncta; early embryogenesis; importin; nuclear pore complex (NPC); nucleoporin; oogenesis

DOI:  https://doi.org/10.1016/j.ydbio.2025.07.001
Development. 2025 Jul 02. pii: dev.204626. [Epub ahead of print]

Deciphering the role of cis-regulatory elements and TFAP2C in the activation of zygotic Sox2 expression in mouse preimplantation embryos.

Jaehwan Kim, Chad S Driscoll, Lijia Li, Catherine A Wilson, Wei Xie, Jason G Knott.

  Cell-fate decisions in preimplantation embryos require the coordinated expression of pluripotency and lineage-specific transcription factors. SOX2 represents the first pluripotency regulator whose expression is restricted to the inside cells of mouse preimplantation embryos. However, the genetic mechanisms that activate the expression of zygotic Sox2 are poorly understood. Here we report that Sox2 expression in mouse embryos is controlled by the actions of key cis-regulatory elements, including a proximal promoter and super enhancer. We show that TFAP2C, a key trophoblast lineage regulator, binds to the Sox2 proximal promoter to activate its expression. Lastly, we provide evidence that TFAP2C and the HIPPO signaling pathway cooperatively regulate Sox2 expression. In summary, this work has important implications in understanding how conventional trophoblast transcription factors, such as TFAP2C, contribute to the activation of early pluripotency genes to facilitate divergent cellular states that support lineage formation.

Keywords:   Sox2 regulatory regions; HIPPO signaling; Pluripotency; Preimplantation embryo; TFAP2C

DOI:  https://doi.org/10.1242/dev.204626
Curr Biol. 2025 Jun 25. pii: S0960-9822(25)00759-6. [Epub ahead of print]

Hybrid incompatibility emerges at the one-cell stage in interspecies Caenorhabditis embryos.

Jessica Bloom, Rebecca A Green, Arshad Desai, Karen Oegema, Scott A Rifkin.

  Intrinsic reproductive isolation occurs when genetic divergence between populations disrupts hybrid development, preventing gene flow and reinforcing speciation.1,2,3,4 Molecular mechanisms explaining a few dozen cases of hybrid incompatibility have been uncovered in animals,5 including mismatches in zygotic gene regulation,6,7,8,9,10,11 symbiont-driven incompatibilities,12 nucleoporin mismatches affecting nuclear-cytoplasmic transport,13 and divergence in centromeric or heterochromatic regions and their regulatory proteins that lead to the inability of the oocyte cytoplasm to segregate sperm-derived chromosomes.14,15,16,17,18,19 Expanding mechanistic work to more diverse taxa is important for elucidating broader patterns of hybrid incompatibility. Here, we investigate hybrid incompatibility in Caenorhabditis elegans group nematodes. Within this group, most species pairs do not mate, and hybrids typically die during embryogenesis in those that do.20,21,22,23,24,25,26 Although individual embryos within a cross arrest at variable time points,27,28 we show that incompatibilities typically originate between fertilization and the 4-cell stage, prior to the onset of zygotic transcription.29,30,31,32 In Caenorhabditis, like most animals,33,34 sperm deliver chromatin and centrioles into the oocyte.35,36,37,38 After oocyte meiosis, the sperm chromatin acquires a nuclear envelope, and centrioles initiate centrosome formation.39,40,41 Centrosomes remain tethered to the sperm pronucleus, which positions them near the cortex to establish anterior-posterior polarity.42,43 We identify two key processes that are destabilized in hybrids: (1) oocyte control of sperm-derived pronuclear expansion and (2) polar body formation. When sperm pronuclear expansion is delayed, centrosomes detach, leading to defects in polarity establishment. Hybrid embryos typically experience one or more failures of early developmental events that accumulate and eventually kill them.

Keywords:  Caenorhabditis nematodes; cell polarity; centrosome attachment; evolutionary cell biology; evolutionary developmental biology; hybrid incompatibility; intrinsic reproductive isolation; mitotic spindle; polar body extrusion; sperm pronuclear expansion

DOI:  https://doi.org/10.1016/j.cub.2025.06.030
J Genet Genomics. 2025 Jun 27. pii: S1673-8527(25)00178-X. [Epub ahead of print]

Cohesin variants and meiotic timing shape chromosome segregation accuracy.

Yuanyuan Liu, Bohan Liu, Shuo Wang, Li Zhao, Qian Li, Feifei Qi, Ruoxi Wang, Jun Zhou, Jinmin Gao.

  The frequency of aneuploid gamete formation increases with maternal age, yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood. Using the multicellular organism Caenorhabditis elegans, we investigate the impact of mutations in the conserved cohesin complex on age-associated meiotic errors. Point mutations in the head domain of the cohesin component SMC-1, which alter local hydrophobicity, cause meiotic defects that vary with age. A severe mutation causes incomplete synapsis and defective crossover formation, and a minor one causes age-related diakinesis bivalent abnormalities. Notably, while the mild mutation causes defects only in aged worms, worms with the severe mutation exhibit significantly alleviated phenotypes with age. Genetic and cytological analyses suggest that this alleviation results from a slowed meiotic progression during early prophase, which restores impaired cohesin loading. These findings reveal that cohesin variants, meiotic progression speed during early prophase, and the overall duration of meiosis collectively shape the accuracy of meiotic chromosome segregation.

Keywords:  Caenorhabditis elegans; Chromosome segregation; Cohesin; Meiosis; Reproductive aging; SMC-1

DOI:  https://doi.org/10.1016/j.jgg.2025.06.003
Histochem Cell Biol. 2025 Jun 28. 163(1): 70

A comprehensive review of histone modifications during mammalian oogenesis and early embryo development.

Nazlican Bozdemir, Tuba Kablan, Efe Biyikli, Ozgur Cinar, Fatma Uysal.

  The success of both oogenesis and early embryo development relies heavily on dynamic epigenetic regulation in which gene activity changes without affecting the underlying DNA sequence. Epigenetics works through two main mechanisms: DNA methylation and histone modifications. DNA methylation typically leads to gene silencing, while histone modifications can either activate or repress genes depending on the specific modification, histone type, and targeted amino acid residue. Histone modifications affect important DNA regulatory processes in which the histone core area as well as the N-terminal tails that extend from the core region are vulnerable to a variety of posttranslational modifications (PTMs), including methylation, citrullination (deimination), acetylation, phosphorylation, ubiquitination, SUMOylation, ribosylation, and lactylation. This review article focuses on what is known about changes in the histone modifications and how these modifications and their responsible enzymes operate throughout mammalian oocyte maturation and early embryo development, highlighting their crucial roles in these processes.

Keywords:  Early embryo development; Epigenetics; Histone modifications; Oogenesis; Preimplantation embryos

DOI:  https://doi.org/10.1007/s00418-025-02398-x
Nat Commun. 2025 Jul 01. 16(1): 5755

An ex vivo uterine system captures implantation, embryogenesis, and trophoblast invasion via maternal-embryonic signaling.

Takehiro Hiraoka, Shizu Aikawa, Daisuke Mashiko, Tatsuya Nakagawa, Hiroki Shirai, Yasushi Hirota, Hiroshi Kimura, Masahito Ikawa.

Embryo implantation remains challenging to study because of its inaccessibility in situ despite its essentiality and clinical significance. Although recent studies on long-term culture of authentic and model embryos have provided significant advances in elucidating embryogenesis in vitro, they, without the uterus, cannot genuinely replicate implantation. Here, we have recapitulated bona fide implantation ex vivo at more than 90% efficiency followed by embryogenesis and trophoblast invasion using authentic mouse embryos and uterine tissue. We utilized air-liquid interface culture method with originally developed devices manufactured with polydimethylsiloxane. Notably, the system replicated the robust induction of a maternal implantation regulator COX-2 at the attachment interface, which was accompanied by trophoblastic AKT activation, suggesting a possible signaling that mediates maternal COX-2 and embryonic AKT1 that accelerates implantation. By expanding the ex vivo findings, embryonic AKT1 transduction ameliorated defective implantation of uterine origin by a COX-2 inhibitor in vivo. The system, proposing a potentially standard platform of embryogenesis, offers a concise, reproducible, and scalable screening system, suggesting significant implications for developmental biology and therapeutic strategies for recurrent implantation failure in assisted reproductive technology.

DOI: https://doi.org/10.1038/s41467-025-60610-x
BMC Genomics. 2025 Jul 01. 26(1): 600

RNA binding protein HuR regulated by OIP5-AS1 may be involved in maternal transcript degradation during the human maternal-to-zygotic transition.

Yan-Na Liu, Ke-Yi Li, Hao Wei, Wen-Xiu Li, Yue-Hua Zhang, Jia-Jun Qiu, Fanyi Zeng, Jing-Bin Yan.

   BACKGROUND: The maternal-to-zygotic transition (MZT) is a critical process in early human development, involving the degradation of maternal gene transcripts and activation of zygotic genes. Any disruption in the degradation of maternal transcripts may be associated with some reproductive disorders. However, the precise mechanism by which maternal gene transcripts are degraded during this transition remains unclear.
RESULTS: Through an analysis of weighted gene co-expression networks, an oocyte-specific module was identified, showing high consistency with the expression pattern of maternal transcripts degraded at the 8-cell stage, which is associated with the cell cycle and transcription factor binding. Within this module, a maternal long non-coding RNA known as OIP5 antisense RNA 1 (OIP5-AS1) was identified. It was observed that OIP5-AS1 can bind to the RNA binding protein human antigen R (HuR), potentially limiting its availability for other mRNAs and contributing to the degradation of maternal transcripts during MZT. Moreover, RNA immunoprecipitation sequencing in human induced pluripotent stem cells (iPSCs) revealed HuR and OIP5-AS1 are likely to tightly bind together and involved in functions related to the cell cycle and transcriptional regulation. Upon knocking down OIP5-AS1 and the ELAVL1 gene, which encodes the HuR protein in human iPSCs, a significant reduction in the expression levels of maternal transcripts was observed, suggesting an essential role of these factors in regulating maternal transcript stability during early development.
CONCLUSIONS: The HuR protein plays a critical role in influencing the degradation of maternal transcripts during the MZT in early human embryonic development. Understanding the role of OIP5-AS1 in regulating HuR protein could provide valuable insights into developmental biology and potentially lead to new therapeutic strategies for developmental disorders.

Keywords:  Early embryonic development; Long non-coding RNAs; Maternal transcript degradation; Maternal-to-zygotic transition; RNA binding protein

DOI:  https://doi.org/10.1186/s12864-025-11807-3
Epigenomics. 2025 Jul 03. 1-9

Mediators of maternal intergenerational epigenetic inheritance in mammals.

Christian Belton, Gavin Kelsey.

  Experimental models and epidemiological data suggest that environmental factors, for example, adverse nutrition prior to conception, can lead to phenotypes in offspring of exposed parents in the absence of continued exposure. As a result these phenotypes have been described as epigentically inherited. The mechanistic basis for such phenomena has not been established in most cases. In this review, we consider possible contributing mechanisms for environmentaly induced epigenetic inheritance, with a focus on maternally transmitted effects and by comparing to paradigms of epigenetic inheritance with a clear mechanistic understanding. Genomic imprinting has provided an important conceptual framework for how the epigenetic states of parental germlines can determine allelic expression in offspring, yet, generally speaking, imprinted genes appear resilient to epigenetic disruption from altered parental environments. Metastable epialleles are environmentally sensitive and variably expressed loci that can impact organism phenotype, but the nature of any epigenetic marker at these loci transferred to offspring is unclear. Studies of examples across these forms of epigenetic inheritance show predominant effects are mediated by oocyte factors involved inreprogramming of the genome post-fertilization, rather than direct effects on gametic DNA methylation, with the exception of genomic imprinting. The potential contribution of additional oocyte chromatin features to the specific liability of phenotypic effector genes and their potential to persist through this reprogramming, however, remains to be investigated.

Keywords:  Epigenetic inheritance; germline; imprinting; maternal effects; metastable epialleles

DOI:  https://doi.org/10.1080/17501911.2025.2525749
Bull Math Biol. 2025 Jun 28. 87(8): 104

On Modeling Ovarian Aging and Menopause Timing.

Sean D Lawley, Nanette Santoro, Joshua Johnson.

Mathematical modeling of ovarian aging and menopause timing has a long history, dating back a half-century to the models of Nobel Prize winner Robert G. Edwards. More recently, such models have been used to investigate clinical interventions for women, which underscores the importance of scientific rigor in model development and analysis. In this paper, we analyze a recent model published in the biophysics literature. We first correct an error which invalidates claims about menopause age in different populations. We then use stochastic analysis to show how this model is a reparameterization of a prior model and put it in the framework of several prior models, which enables the application of extreme value theory. We prove some general extreme value theory results and use them to obtain detailed estimates of menopause age in this model. In particular, we derive a new expected menopause age formula which is orders of magnitude more accurate than the previous heuristic estimate. We further obtain rigorous analytical estimates of the full menopause age distribution and all its moments. We conclude by using these mathematical results to elucidate the physiological sources of menopause age variability.

DOI: https://doi.org/10.1007/s11538-025-01481-7
Sci Rep. 2025 Jul 01. 15(1): 21751

Role of mitochondrial dynamics in mouse preimplantation embryonic development and its molecular mechanisms.

Xiaoyan Sun, Qingyang Li, Bo Chen.

  This study investigated the impact of mitochondrial dynamics on mouse preimplantation embryonic development and its underlying molecular mechanisms. Using pharmacological and genetic approaches, we demonstrated that balanced mitochondrial fusion and fission are essential for optimal embryonic development. Disruption of mitochondrial dynamics significantly impaired blastocyst formation, altered cell lineage allocation, and compromised energy metabolism. Our findings revealed that mitochondrial dynamics regulate gene expression through epigenetic modifications and influence cell survival through the modulation of apoptotic pathways. We also identified key metabolic intermediates and signaling pathways that mediate the effects of mitochondrial dynamics on embryonic development. These results provide new insights into the molecular mechanisms linking mitochondrial function to early embryonic development and suggest potential strategies for improving assisted reproductive technologies.

Keywords:  Apoptosis; Cell fate; Energy metabolism; Epigenetic modification; Mitochondrial dynamics; Mitochondrial fission; Mitochondrial fusion; Mouse embryo; Preimplantation embryonic development; Reproductive biology

DOI:  https://doi.org/10.1038/s41598-025-05622-9