bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–08–10
sixteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations.
  2. Eliminating separase inhibition reveals absence of robust cohesin protection in oocyte metaphase II.
  3. Evaluating Selective Quality Control in Mammalian Oogenesis: Evidence and Opportunities.
  4. Polycomb Repressive-Deubiquitinase Complex Safeguards Oocyte Epigenome and Female Fertility by Restraining Polycomb Activity.
  5. Context is everything: The role of polo-like kinase I during C. elegans oocyte meiosis.
  6. Basal autophagy during meiotic prophase I is required for accurate chromosome segregation in Drosophila oocytes and declines during oocyte aging.
  7. Preparation of Meiotic Chromosome Spreads from Mouse Oocytes for Assessment of Synapsis and Recombination.
  8. Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation.
  9. Generative model for the first cell fate bifurcation in mammalian development.
  10. Quantitative modeling of mRNA degradation reveals tempo-dependent mRNA clearance in early embryos.
  11. Unsaturated Fatty Acids Are Required for Germline Proliferation and Membrane Structural Integrity in Caenorhabditis elegans.
  12. Hypothesis: Germline rejuvenation during meiosis underlies animal oogenesis.
  13. The Drosophila ovarian terminal filament imports molecules needed to produce lipid droplets, the fusome, and functional germ cells.
  14. The Src family kinases contribute to MII arrest maintenance in aging porcine oocytes.
  15. Obox1 deficiency impairs fertility in female mice.
  16. Transcription Factor TCF12-Mediated Maternal Gene Expressions in Mouse Oocyte Are Prerequisites of Successful Fertilisation and Zygotic Genome Activation.
  1. Sci Adv. 2025 Aug 08. 11(32): eadw4954
    Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations.
    Barbara Arbeithuber, Kate Anthony, Bonnie Higgins, Peter Oppelt, Omar Shebl, Irene Tiemann-Boege, Francesca Chiaromonte, Thomas Ebner, Kateryna D Makova.
      Mitochondria, cellular powerhouses, harbor DNA [mitochondrial DNA (mtDNA)] inherited from the mothers. mtDNA mutations can cause diseases, yet whether they increase with age in human oocytes remains understudied. Here, using highly accurate duplex sequencing, we detected de novo mutations in single oocytes, blood, and saliva in women 20 to 42 years of age. We found that, with age, mutations increased in blood and saliva but not in oocytes. In oocytes, mutations with high allele frequencies were less prevalent in coding than noncoding regions, whereas mutations with low allele frequencies were more uniformly distributed along the mtDNA, suggesting frequency-dependent purifying selection. Thus, mtDNA in human oocytes is protected against accumulation of mutations with aging and having functional consequences. These findings are particularly timely as humans tend to reproduce later in life.
    DOI:  https://doi.org/10.1126/sciadv.adw4954
  2. EMBO J. 2025 Aug 05.
    Eliminating separase inhibition reveals absence of robust cohesin protection in oocyte metaphase II.
    Safia El Jailani, Damien Cladière, Elvira Nikalayevich, Sandra A Touati, Vera Chesnokova, Shlomo Melmed, Eulalie Buffin, Katja Wassmann.
      The meiotic segregation pattern to generate haploid gametes is mediated by step-wise cohesion removal by separase, first from chromosome arms in meiosis I, and then from the pericentromere in meiosis II. In mammalian oocytes, separase is tightly controlled during the hours-long prometaphase and until chromosome segregation in meiosis I, activated for a short time window, and again inhibited until metaphase II arrest is lifted by fertilization. Centromeric cohesin is protected from cleavage by Sgo2-PP2A in meiosis I. It remained enigmatic how tight control of alternating separase activation and inactivation is achieved during the two divisions in oocytes, and when cohesin protection is put in place and removed. Using complementation assays in knock-out mouse models, we established the contributions of cyclin B1 and securin for separase inhibition during both divisions. When eliminating separase inhibition, we found that cohesin is not robustly protected at meiosis I resumption and during metaphase II arrest. Importantly, in meiosis II, the sole event required for cleavage of pericentromeric cohesin besides separase activation is prior kinetochore individualization in meiosis I.
    Keywords:  Cohesin Protection; Kinetochore Individualization; Meiosis; Oocytes; Separase Inhibition
    DOI:  https://doi.org/10.1038/s44318-025-00522-0
  3. Annu Rev Genet. 2025 Aug 08.
    Evaluating Selective Quality Control in Mammalian Oogenesis: Evidence and Opportunities.
    Jay W Zussman, Dominic J Skinner, Daniel E Wagner, Stanislav Y Shvartsman, Diana J Laird.
      The formation and maintenance of the finite mammalian ovarian reserve are critical for fertility and species survival. Genetic and developmental studies have uncovered various mechanisms underlying oocyte development and maturation, revealing two curious features of the ovarian germline: (a) The establishment of the follicle reserve involves an initial massive overproduction of oocyte precursors, and (b) the total number of ovulated oocytes across an animal's fertile lifetime is a very small proportion of the initial ovarian reserve. Many have proposed that this indicates the existence of selective quality control to ensure gamete fitness. Here, we review the findings underlying the hypotheses for germline quality control during prepubertal development, homeostatic fertility, and reproductive aging. We evaluate whether the existing evidence base distinguishes the active selection of specific germ cell subsets from neutral dynamics. Throughout, we discuss strategies for applying statistical frameworks to evaluate selection in oogenesis and the implications of neutrality versus selection at various points in oocyte development.
    DOI:  https://doi.org/10.1146/annurev-genet-021925-093551
  4. bioRxiv. 2025 Jul 28. pii: 2025.07.24.666633. [Epub ahead of print]
    Polycomb Repressive-Deubiquitinase Complex Safeguards Oocyte Epigenome and Female Fertility by Restraining Polycomb Activity.
    Jinwen Kang, Peiyao Liu, Shoko Ichimura, Lauryn Cook, Zhiyuan Chen.
      Mouse oocytes exhibit a unique chromatin landscape characterized by broad H3K27ac and H3K27me3 domains, demarcating euchromatin and facultative heterochromatin, respectively. However, the mechanisms underlying this non-canonical landscape remain elusive. Here we report BAP1, a core component of the Polycomb Repressive-Deubiquitinase (PR-DUB) complex, as a key negative regulator of Polycomb activity during oogenesis. BAP1 restricts pervasive H2AK119ub1 accumulation in oocytes and protects oocyte-specific broad H3K27ac, particularly within gene-poor regions, from ectopic H3K27me3 deposition. While PR-DUB has been linked to gene repression, in oocytes BAP1 primarily promotes transcription and contributes minimally to Polycomb-mediated silencing. BAP1-dependent transcriptional activation is essential for oocyte developmental competence and female fertility. BAP1 loss disrupts the maternal-to-zygotic transition and impairs embryonic enhancer activation, ultimately compromising preimplantation development. Notably, while H3K27ac patterns are reset after fertilization, the aberrant H3K27me3 landscape established in BAP1-deficient oocytes persists in early embryos. Together, these findings reveal a critical role for PR-DUB in safeguarding the oocyte epigenome by protecting euchromatin from ectopic Polycomb activity, rather than enforcing transcriptional repression.
    DOI:  https://doi.org/10.1101/2025.07.24.666633
  5. J Cell Biol. 2025 Sep 01. pii: e202506208. [Epub ahead of print]224(9):
    Context is everything: The role of polo-like kinase I during C. elegans oocyte meiosis.
    Needhi Bhalla.
      Meiotic chromosome segregation in oocytes often relies on meiosis-specific modifications of mitotic molecular mechanisms to respond to the unique challenges of this asymmetric division. In this issue, Narula and Wignall (https://doi.org/10.1083/jcb.202503080) demonstrate how the conserved polo-like kinase in Caenorhabditiselegans, PLK-1, has been repurposed in unexpected ways to ensure accurate meiotic chromosome segregation during oogenesis.
    DOI:  https://doi.org/10.1083/jcb.202506208
  6. Mol Biol Cell. 2025 Aug 06. mbcE25050213
    Basal autophagy during meiotic prophase I is required for accurate chromosome segregation in Drosophila oocytes and declines during oocyte aging.
    Diana C Hilpert, Muhammad Abdul Haseeb, Sharon E Bickel.
      Meiotic segregation errors in human oocytes are the leading cause of miscarriages and trisomic pregnancies and their frequency increases exponentially for women in their thirties. One factor that contributes to increased segregation errors in aging oocytes is premature loss of sister chromatid cohesion. However, the mechanisms underlying age-dependent deterioration of cohesion are not well-defined. Autophagy, a cellular degradation process critical for cellular homeostasis, is known to decline with age in various organisms and cell types. Here we quantify basal autophagy in Drosophila oocytes and use GAL4/UAS inducible knockdown to ask whether disruption of autophagy in prophase oocytes impacts the fidelity of chromosome segregation. We find that individual knockdown of autophagy proteins in Drosophila oocytes during meiotic prophase causes a significant increase in segregation errors. In addition, Atg8a knockdown in prophase oocytes leads to premature loss of arm cohesion and missegregation of recombinant homologs during meiosis I. Using an oocyte aging paradigm that we have previously described, we show that basal autophagy decreases significantly when Drosophila oocytes undergo aging. Our data support the model that a decline in autophagy during oocyte aging contributes to premature loss of meiotic cohesion and segregation errors.
    DOI:  https://doi.org/10.1091/mbc.E25-05-0213
  7. J Vis Exp. 2025 Jul 18.
    Preparation of Meiotic Chromosome Spreads from Mouse Oocytes for Assessment of Synapsis and Recombination.
    Tegan S A Horan.
      Three critical and interdependent processes define meiotic prophase I: homologous chromosomes must pair together, a proteinaceous structure called the synaptonemal complex forms to tether homologs together (synapsis), and homologs undergo recombination, reciprocally exchanging genetic material to form crossovers (COs). Errors in these processes can result in premature ovarian insufficiency, aneuploidy, and ultimately, pregnancy loss and infertility. Meiotic recombination is particularly error-prone in oocytes, with over 7% of human oocytes containing at least one chromosome pair without a crossover, and between 20%-80% of eggs versus 2.5%-7% of sperm are aneuploid. However, it remains unclear why chromosomal errors show such striking sex disparities. The present protocol describes methods for the preparation and analysis of oocyte prophase I and metaphase I chromosome spreads from fetal and juvenile mice, respectively. To trace critical chromosome dynamics throughout meiotic prophase I, this protocol employs immunofluorescence staining of common markers for meiotic recombination (RAD51 for double strand breaks, MSH4 for CO intermediates, and MLH1/MLH3 to identify most COs) and synapsis (SYCP3 for chromosome axes, SYCP1 for synapsed regions, and HORMAD1 for asynapsed regions). Further, this protocol uses in vitro maturation of oocytes collected to assess the number of paired chromosomes (bivalents) and the total number of crossovers (chiasmata) in metaphase I. Together, these techniques provide a comprehensive and quantitative framework to examine mechanisms regulating early chromosome dynamics in female meiosis.
    DOI:  https://doi.org/10.3791/68749
  8. bioRxiv. 2025 Jul 28. pii: 2025.07.23.666394. [Epub ahead of print]
    Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation.
    Catherine A Tower, Gabriel Manske, Emily L Ferrell, Dilara N Anbarci, Kelsey Jorgensen, Binbin Ma, Mansour Aboelenain, Rajesh Ranjan, Saikat Chakraborty, Lindsay Moritz, Arunika Das, Michele Boiani, Ben E Black, Shawn Chavez, Erica E Marsh, Ariella Shikanov, Karen Schindler, Xin Chen, Saher Sue Hammoud.
      Across metazoan species, the centromere-specific histone variant CENP-A is essential for accurate chromosome segregation, yet its regulation at the parental-to-zygote transition in mammals is poorly understood. To address this, we developed a CENP-A-mScarlet knock-in mouse model, which revealed sex-specific dynamics: mature sperm retains 10% of the CENP-A levels present in MII-oocytes. However, in zygotes prior to the first mitosis, this difference is resolved, using maternally inherited cytoplasmic-CENP-A. Notably, the increase in CENP-A at paternal centromeres is independent of sensing CENP-A asymmetry or the presence of maternal chromosomes. Instead, CENP-A equalization relies on asymmetric recruitment of maternal CENP-C to paternal centromeres. Depletion of maternal CENP-A decreases total CENP-A in pronuclei without disrupting equalization. In contrast, reducing maternal CENP-C or disruption of its dimerization domains impairs CENP-A equalization and chromosome segregation. Therefore, maternal CENP-C acts a key epigenetic regulator that resets centromeric symmetry at fertilization to preserve genome integrity.
    Highlights: CENP-A asymmetry between sperm and oocyte centromeres is a conserved feature from flies to mammals including mice and humans.CENP-A asymmetry between parental centromeres is resolved prior to the first zygotic division via maternally inherited, cytoplasmic CENP-A.Zygotic CENP-A levels in zygotes are regulated in a pronucleus-autonomous manner.CENP-A equalization relies on asymmetric CENP-C recruitment to the paternal pronucleus and requires CENP-C dimerization.
    Key Terms: Centromere; CENP-A; CENP-C; sperm; oocyte; zygote; intergenerational; epigenetics; mouse.
    DOI:  https://doi.org/10.1101/2025.07.23.666394
  9. Development. 2025 Aug 05. pii: dev.204717. [Epub ahead of print]
    Generative model for the first cell fate bifurcation in mammalian development.
    Maria Avdeeva, Madeleine Chalifoux, Bradley Joyce, Stanislav Y Shvartsman, Eszter Posfai.
      The first cell fate bifurcation in mammalian development directs cells toward either the trophectoderm (TE) or inner cell mass (ICM) compartments in preimplantation embryos. This decision is regulated by the subcellular localization of a transcriptional co-activator YAP and takes place over several progressively asynchronous cleavage divisions. As a result of this asynchrony and variable arrangement of blastomeres, reconstructing the dynamics of the TE/ICM cell specification from fixed embryos is extremely challenging. To address this, we developed a live imaging approach and applied it to measure pairwise dynamics of nuclear YAP and its direct target genes, CDX2 and SOX2, key transcription factors of TE and ICM, respectively. Using these datasets, we constructed a generative model of the first cell fate bifurcation, which reveals the time-dependent statistics of the TE and ICM cell allocation. In addition to making testable predictions for the joint dynamics of the full YAP/CDX2/SOX2 motif, the model revealed the stochastic nature of the induction timing of the key cell fate determinants and identified the features of YAP dynamics that are necessary or sufficient for this induction. Notably, temporal heterogeneity was particularly prominent for SOX2 expression among ICM cells. As heterogeneities within the ICM have been linked to the initiation of the second cell fate decision in the embryo, understanding the origins of this variability is of key significance. The presented approach reveals the dynamics of the first cell fate choice and lays the groundwork for dissecting the next cell fate decisions in mouse development.
    Keywords:  Bayesian modeling; First cell fate decision; Live imaging; Mouse; Preimplantation
    DOI:  https://doi.org/10.1242/dev.204717
  10. Nucleic Acids Res. 2025 Jul 19. pii: gkaf737. [Epub ahead of print]53(14):
    Quantitative modeling of mRNA degradation reveals tempo-dependent mRNA clearance in early embryos.
    Mazal Tawil, Dina Alcalay, Pnina Greenberg, Shirel Har-Sheffer, Lior Fishman, Michal Rabani.
      As embryos transition from maternal to zygotic control, precise clearance of pre-loaded maternal mRNAs is essential for initiating new zygotic gene expression programs. Yet the kinetics of this process and how it adapts across different developmental speeds remain unclear. Here, we introduce QUANTA, a computational approach that uses time-series RNA-seq data to quantify mRNA turnover and polyadenylation dynamics of transcriptionally silent genes and find related regulatory motifs. Applying QUANTA to zebrafish, frog, mouse, and human embryos, we uncover a conserved regulatory logic: maternal mRNA degradation onset and rates align with species' developmental tempo. However, a subset of transcripts deviates from this pattern, suggesting species-specific kinetic tuning, which is further supported by the distinct use of destabilizing 3'UTR motifs in fast-developing species. Using temperature-based manipulation of zebrafish developmental speed and a high-throughput reporter assay, we reveal a regulatory logic of mRNA degradation scaling. Unstable mRNAs are not well-adapted to altered tempos, but scaling improves when enhancing stability through poly(A) tails or 3'UTR motifs. We demonstrate the tempo-sensitive function of 3'UTR motifs, linking regulatory sequences with developmental scaling. Our work establishes a quantitative framework for investigating mRNA turnover and reveals how clearance dynamics is tuned to match developmental pace.
    DOI:  https://doi.org/10.1093/nar/gkaf737
  11. bioRxiv. 2025 Jul 29. pii: 2025.07.24.666670. [Epub ahead of print]
    Unsaturated Fatty Acids Are Required for Germline Proliferation and Membrane Structural Integrity in Caenorhabditis elegans.
    Bernabe Battista, Laura I Lascarez-Lagunas, Diego de Mendoza, Monica P Colaiácovo.
      Unsaturated fatty acids (UFAs) are critical components of membrane lipids, but their specific roles in germline development and reproductive health remain poorly defined. Here, we investigated the consequences of UFA depletion in the Caenorhabditis elegan s germline using an auxin-inducible degron (AID) system to conditionally degrade FAT-7, the major Δ9 stearoyl-CoA desaturase, in a fat-5; fat-6 double mutant background. This strategy bypassed the lethality associated with complete loss of Δ9 desaturase activity, enabling analysis of UFA deficiency in adult animals. UFA depletion led to a dramatic reduction in brood size, elevated embryonic and larval lethality, and a severe loss of germline nuclei. We found that UFAs are essential for mitotic proliferation, DNA replication, and chromosome organization in the germline. Moreover, reduced UFA levels impaired meiotic progression, accompanied by loss of membrane integrity in the syncytial germline. Notably, UFA deficiency increased nuclear pore complex (NPC) signal intensity, suggesting alterations to the nuclear envelope (NE). Together, our findings demonstrate that UFAs are indispensable for germline maintenance, affecting cell cycle progression, chromosome organization, and membrane architecture. These results underscore a fundamental link between acyl chain composition and reproductive success, highlighting the critical role of lipid homeostasis in the germline.
    Summary: Unsaturated fatty acids (UFAs) are essential for fertility, but their role in germline maintenance remains unclear. In this study, we used Caenorhabditis elegans to examine how UFA depletion affects the germline. By conditionally disrupting UFA synthesis, we found that low UFA levels impair germline mitotic proliferation, DNA replication, meiotic progression, and germline membrane structures. These findings demonstrate that lipid composition is critical for germline maintenance and highlight a broader role for fatty acids in reproductive health, offering insights relevant to metabolic and fertility disorders in humans.
    DOI:  https://doi.org/10.1101/2025.07.24.666670
  12. Dev Biol. 2025 Aug 04. pii: S0012-1606(25)00213-1. [Epub ahead of print]
    Hypothesis: Germline rejuvenation during meiosis underlies animal oogenesis.
    Spradling A, Pathak M, Davidian A, Maurya B, Tiwari A, Yin Q, Fu Y, Mao A.
      Animal oogenesis utilizes features shared among diverse phylogenetic groups, whose functional roles in promoting progeny development have remained unclear. However, germ cells not only produce the next generation, they also maintain long term species integrity by fully restoring acquired damage that deviates from genomic specifications and by controlling parasitic elements that pose a multi-generational threat. Here we discuss how oogenesis "rejuvenates" the germline to sustain the effective immortality needed for species to survive, adapt and evolve. We argue that animal oocytes actively rebuild critical critical cellular components including organelles during meiosis, usually within an ancient syncytial format, the germline cyst, that enhances renewal mechanisms long inherent to meiosis in single-celled eukaryotes. The Balbiani body accumulates rejuvenated materials and connects them with germ cell inducers relatively early in oogenesis, to ensure genome-quality constituents are inherited by germ cells of the next generation. This strategy explains the existence of germ plasm and why the GV-Bb axis presages the embryo's animal-vegetal axis in diverse species. The advent of a more powerful rejuvenation system may have enabled the evolution of animals.
    DOI:  https://doi.org/10.1016/j.ydbio.2025.08.002
  13. bioRxiv. 2025 Jul 31. pii: 2025.07.30.667757. [Epub ahead of print]
    The Drosophila ovarian terminal filament imports molecules needed to produce lipid droplets, the fusome, and functional germ cells.
    Bhawana Maurya, Allan C Spradling.
      Insect ovarioles typically begin with a protruding stack of flat cells known as the terminal filament (TF) located just upstream from germline stem cells (GSCs) in the germarium. However, terminal filament function has not been clearly established. We selectively knocked down genes only in TF cells using GAL4 driven by the TF-specific transcription factor bric-a-brac 1 (bab1). TF-specific loss of transporters or vesicle trafficking genes showed that terminal filament cells import molecules, transfer them through the cellular stack, and deposit near the GSC niche, a process required for ongoing oocyte production and to generate germ cell lipid droplets and fusomes. Loss of organic anion transporter Oatp30B in the TF blocked the development of GSC daughters (cystoblasts), implicating the TF in importing molecules needed for cyst and oocyte development, possibly including an endogenous ouabain. These experiments show the terminal filament imports lipids into the ovary, and is essential for germ cell development =[]]''''''''and oocyte production.
    DOI:  https://doi.org/10.1101/2025.07.30.667757
  14. Theriogenology. 2025 Aug 02. pii: S0093-691X(25)00340-1. [Epub ahead of print]248 117614
    The Src family kinases contribute to MII arrest maintenance in aging porcine oocytes.
    Kateřina Kheilová, Jaroslav Petr, Dalibor Řehák, Eva Chmelíková, Markéta Sedmíková.
      Mature mammalian oocytes arrest meiosis in metaphase II (MII). If the oocyte is not fertilized, it can spontaneously break the MII arrest. Spontaneous activation and postovulatory aging hinder precisely timed and regulated embryonic development. To elucidate the role of Src family protein tyrosine kinases (SFKs) in porcine oocyte MII arrest, activation, and aging, we used a specific SFK inhibitor and immunolocalization. The 24h-prolonged oocyte culture in the presence of SFK inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) increased (P < 0.05) the proportion of spontaneously activated porcine oocytes compared to controls. Further culture with PP2 inhibitor led to an increase (P < 0.05) in the parthenogenetic embryos and a decrease (P < 0.05) in lytic oocytes. SFK inhibition did not affect (P > 0.05) the proportion of ionophore A23187-activated oocytes. SFKs were localized in the perichromosomal region, in the pronuclei, in the cytoplasm, and on the plasma membrane of oocytes and parthenogenetic embryos after 24, 48, and 72 h of prolonged in vitro culture. The greatest SFKs fluorescence was detected after a 24h-prolonged culture on the plasma membrane of MII oocytes. In embryos and fragmented oocytes, intense fluorescence was detected in the cleavage furrow region and on the membrane of apoptotic vesicles, respectively. Our results reveal the involvement of SFKs in MII arrest maintenance, though they don't appear to modulate the early processes of ionophore-stimulated parthenogenetic activation. Changes in the distribution of SFKs during prolonged culture suggest their role in signaling cascades associated with actin filament cytoskeleton organization.
    Keywords:  Meiotic arrest; Pig; Postovulatory aging; Tyrosine kinases
    DOI:  https://doi.org/10.1016/j.theriogenology.2025.117614
  15. Fundam Res. 2025 Jul;5(4): 1570-1580
    Obox1 deficiency impairs fertility in female mice.
    Li Wu, Jiacheng Shen, Zhenzhen Hou, Yinli Zhang, Yan Bi, Ran Zhang, Heping Bai, Wen Ye, Kang Chen, Jiang Zhu, Chenxiang Xi, Yiliang Xu, Xiaochen Kou, Yanhong Zhao, Chong Li, Hengyu Fan, Rongrong Le, Yixuan Wang, Xiaocui Xu, Shaohua Xu, Hong Wang, Shaorong Gao, Lan Kang.
      OBOX1 is a maternal factor involved in oogenesis and follicle development, yet its specific role remains unclear. Here, we demonstrated that Obox1 knockout female mice exhibit subfertility, characterized by reduced litter size and impaired ovulation. These oocytes show minimal disruption in early embryonic development post-fertilization. However, Obox1 deficiency leads to decreased levels of gonadotropins and female sex hormones, especially the luteinizing hormone (LH). Exogenous human chorionic gonadotropin (hCG) administration during superovulation failed to rescue the ovulation defect. Post-ovulation, the ovulation-related genes and serum progesterone levels were significantly reduced in Obox1-deficienct ovaries, accompanied by dysregulated steroidogenesis-related gene expression. Transcriptomic profiling of Obox1 deficient metaphase II (MII) oocytes revealed downregulation of genes involved in mitochondrial energy metabolism and biosynthesis, and upregulation of genes associated with cell transport, transcription, RNA processing, translation. Further investigation revealed that follistatin gene expression was upregulated in both MII oocytes and ovaries of Obox1 deficient mice, along with increased expression of Gdf9, Bmp15, Foxl2, and NOTCH signaling components. These findings suggest that Obox1 is essential for maintaining hormonal balance and ovulatory function through regulating oocyte-granulosa cell interactions and steroid hormone synthesis.
    Keywords:  Aberrant steroidogenesis; Abnormal luteinization; Hormone deficiency; Oocyte-granulosa cell interactions; Subfertility
    DOI:  https://doi.org/10.1016/j.fmre.2025.04.008
  16. Cell Prolif. 2025 Aug 03. e70110
    Transcription Factor TCF12-Mediated Maternal Gene Expressions in Mouse Oocyte Are Prerequisites of Successful Fertilisation and Zygotic Genome Activation.
    Lan-Rui Cao, Chi Zhang, Zuo-Qi Deng, Yue-Xin Qiu, Zhao Zhang, Heng-Yu Fan, Jing Li, Hong-Bo Wu.
      The maternal gene products stored in oocytes control the initial development of multicellular animals. Alteration within the dual allelic variants of transcription factor TCF12 causes female infertility; however, its impact on female reproduction is still unknown. In this study, we provide evidence that TCF12 is abundantly expressed within the nucleus of oocytes during growth at the germinal vesicle (GV) stage, recognising and binding to the functional domain of target genes to moderate transcriptional activity. The absence of Tcf12 in oocytes during the primordial follicular phase causes female sterility. Tcf12 does not participate in meiotic maturation; however, unlike Tcf3, it is essential for fertilisation and preimplantation development. Tcf12 maintains fertilisation competence by controlling the proper expression and location of cortical granules and protease ovastacin (encoded by Astl). In contrast, zygotes without TCF12 have a prolonged mitotic cell cycle upon a decrease in protein phosphatase 2A (PP2A) activity inhibition, resulting in zygotic genome activation (ZGA) failure during the 2-cell stage. Maternal knockout embryos gradually lose their developmental potential in subsequent developmental processes. These observations indicate that the maternal effect induced by Tcf12 ensures preimplantation development.
    Keywords:  cell cycle; fertilisation; oocyte; preimplantation embryos; reproduction; transcription factor; zygotic genome activation
    DOI:  https://doi.org/10.1111/cpr.70110
This page is being maintained by Thomas Krichel. It was last updated on 2025‒08‒10 at 7:24.