bims-cebooc 2025-03-16 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2025–03–16
sixteen papers selected by
Gabriele Zaffagnini, Universität zu Köln

GSK3 coordinately regulates mitochondrial activity and nucleotide metabolism in quiescent oocytes.
Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.
Single-nucleus multiomics reveals the gene regulatory networks underlying sex determination of murine primordial germ cells.
A versatile cohesion manipulation system reveals CENP-A dysfunction accelerates female reproductive age-related egg aneuploidy.
Dysregulation of the actin cytoskeleton and FMRP causes polar body protrusion defects in human fragile X premutation and aged oocytes.
Generation of primordial germ cell-like cells by two germ plasm components, dnd1 and nanos3, in medaka (Oryzias latipes).
Overlapping and separable activities of BRA-2 and HIM-17 promote occurrence and regulation of pairing and synapsis during Caenorhabditis elegans meiosis.
FG repeats drive co-clustering of nuclear pores and P granules in the C. elegans germline.
Follicular metabolic dysfunction, oocyte aneuploidy and ovarian aging: a review.
The asymmetric expression of HSPA2 in blastomeres governs the first embryonic cell-fate decision.
Inhibition of HDAC4 in granulosa cells improved co-cultured oocyte maturation in vitro independent of LH in porcine.
A nuclear pore-anchored condensate enables germ granule organization and transgenerational epigenetic inheritance.
Generative model for the first cell fate bifurcation in mammalian development.
Geometric, cell cycle and maternal-to-zygotic transition-associated YAP dynamics during preimplantation embryo development.
Hyper-ovulation in an ovarian-specific transgenic mouse model.
Multifaceted regulation of asymmetric cell division by the actin cytoskeleton.

Biol Open. 2025 Mar 06. pii: bio.061815. [Epub ahead of print]

GSK3 coordinately regulates mitochondrial activity and nucleotide metabolism in quiescent oocytes.

Leah Eller, Lei Wang, Mehmet Oguz Gok, Helin Hocaoglu, Shenlu Qin, Parul Gupta, Matthew H Sieber.

  As cells transition between periods of growth and quiescence, their metabolic demands change. During this transition, cells must coordinate changes in mitochondrial function with the induction of biosynthetic processes. Mitochondrial metabolism and nucleotide biosynthesis are key rate-limiting factors in regulating early growth. However, it remains unclear what coordinates these mechanisms in developmental systems. Here, we show that during quiescence, as mitochondrial activity drops, nucleotide breakdown increases. However, at fertilization, mitochondrial oxidative metabolism and nucleotide biosynthesis are coordinately activated to support early embryogenesis. We have found that the serine/threonine kinase GSK3 is a key factor in coordinating mitochondrial metabolism with nucleotide biosynthesis during transitions between quiescence and growth. Silencing GSK3 in quiescent oocytes causes increased levels of mitochondrial activity and a shift in the levels of several redox metabolites. Interestingly, silencing GSK3 in quiescent oocytes also leads to a precocious induction of nucleotide biosynthesis in quiescent oocytes. Taken together, these data indicate that GSK3 functions to suppress mitochondrial oxidative metabolism and prevent the premature onset of nucleotide biosynthesis in quiescent eggs. These data reveal a key mechanism that coordinates mitochondrial function and nucleotide synthesis with fertilization.

Keywords:  Drosophila; Embryo; Metabolism; Mitochondria; Oocyte

DOI:  https://doi.org/10.1242/bio.061815
Nat Med. 2025 Mar 11.

Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.

Estonian Biobank Research Team

The genetic background of many female reproductive health diagnoses remains uncharacterized, compromising our understanding of the underlying biology. Here, we map the genetic architecture across 42 female-specific health conditions using data from up to 293,618 women from two large population-based cohorts, the Estonian Biobank and the FinnGen study. Our study illustrates the utility of genetic analyses in understanding women's health better. As specific examples, we describe genetic risk factors for ovarian cysts that elucidate the genetic determinants of folliculogenesis and, by leveraging population-specific variants, uncover new candidate genes for uterine fibroids. We find that most female reproductive health diagnoses have a heritable component, with varying degrees of polygenicity and discoverability. Finally, we identify pleiotropic loci and genes that function in genital tract development (WNT4, PAX8, WT1, SALL1), hormonal regulation (FSHB, GREB1, BMPR1B, SYNE1/ESR1) and folliculogenesis (CHEK2), underlining their integral roles in female reproductive health.

DOI: https://doi.org/10.1038/s41591-025-03543-8
Elife. 2025 Mar 10. pii: RP96591. [Epub ahead of print]13

Single-nucleus multiomics reveals the gene regulatory networks underlying sex determination of murine primordial germ cells.

Adriana K Alexander, Karina F Rodriguez, Yu-Ying Chen, Ciro Amato, Martin A Estermann, Barbara Nicol, Xin Xu, Humphrey H C Yao.

  Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial germ cells (PGCs) are the bipotential precursors of mature gametes that commit to an oogenic or spermatogenic fate in response to sex-determining cues from the fetal gonad. The critical processes required for PGCs to integrate and respond to signals from the somatic environment in gonads are not well understood. In this study, we developed the first single-nucleus multiomics map of chromatin accessibility and gene expression during murine PGC development in both XX and XY embryos. Profiling of cell-type-specific transcriptomes and regions of open chromatin from the same cell captured the molecular signatures and gene networks underlying PGC sex determination. Joint RNA and ATAC data for single PGCs resolved previously unreported PGC subpopulations and cataloged a multimodal reference atlas of differentiating PGC clusters. We discovered that regulatory element accessibility precedes gene expression during PGC development, suggesting that changes in chromatin accessibility may prime PGC lineage commitment prior to differentiation. Similarly, we found that sexual dimorphism in chromatin accessibility and gene expression increased temporally in PGCs. Combining single-nucleus sequencing data, we computationally mapped the cohort of transcription factors that regulate the expression of sexually dimorphic genes in PGCs. For example, the gene regulatory networks of XX PGCs are enriched for the transcription factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, and ZFX. Sex-specific enrichment of the forkhead-box and POU6 families of transcription factors was also observed in XY PGCs. Finally, we determined the temporal expression patterns of WNT, BMP, and RA signaling during PGC sex determination, and our discovery analyses identified potentially new cell communication pathways between supporting cells and PGCs. Our results illustrate the diversity of factors involved in programming PGCs toward a sex-specific fate.

Keywords:  developmental biology; germ cell; gonad; mouse; ovary; primordial germ cells; sex differentiation; single cell sequencing; testis

DOI:  https://doi.org/10.7554/eLife.96591
bioRxiv. 2025 Feb 27. pii: 2025.02.27.640570. [Epub ahead of print]

A versatile cohesion manipulation system reveals CENP-A dysfunction accelerates female reproductive age-related egg aneuploidy.

Jiyeon Leem, Tom Lemonnier, Ani Khutsaidze, Lei Tian, Xiaojun Xing, Suxia Bai, Timothy Nottoli, Binyam Mogessie.

Female reproductive aging is accompanied by a dramatic rise in the incidence of egg aneuploidy. Premature loss of chromosome cohesion proteins and untimely separation of chromosomes is thought to underly high rates egg aneuploidy during maternal aging. However, because chromosome cohesion loss occurs gradually over female reproductive lifespan and cytoskeletal defects alone can predispose eggs to chromosomal abnormalities, the root causes of exponential rise in egg aneuploidy at advanced reproductive ages remain a mystery. Here, we applied high-resolution live imaging to visualize for the first time cohesion protein dynamics underpinning meiotic chromosome segregation. To discover proteins whose dysfunction accelerates aneuploidies associated with female reproductive aging, we innovated the first experimental system in which chemically induced cohesion reduction rapidly triggers aging-like chromosomal abnormalities in young eggs. By integrating this direct cohesion manipulation system with quantitative high-resolution microscopy and targeted protein degradation tools, we identified the centromeric protein CENP-A as a new factor whose aging-like depletion causes a dramatic rise in premature separation of sister chromatids. Our work illuminates cohesion loss-independent origins of age-related egg aneuploidy and provides new avenues to discover therapeutic targets for extending the female reproductive lifespan.

DOI: https://doi.org/10.1101/2025.02.27.640570
bioRxiv. 2025 Feb 26. pii: 2025.02.23.639319. [Epub ahead of print]

Dysregulation of the actin cytoskeleton and FMRP causes polar body protrusion defects in human fragile X premutation and aged oocytes.

Kelly McCarter, Madhura Deshpande, Phillip Romanski, Christina Anna Stratopoulou, Nikica Zaninovic, Momina Tareen, Razan Al-Mousawi, Daylon James, Advaitha Madireddy, Zev Rosenwaks, Jeannine Gerhardt.

Women carrying the fragile X premutation (55-200 CGG repeat expansion, PM) are at risk for developing fragile X-associated primary ovarian insufficiency (FXPOI), which is preceded by fragile X-associated diminished ovarian reserve (FXDOR). So far, the cause of FXDOR/FXPOI could not be comprehensively examined due to the scarcity of human ovarian tissue and oocytes. From studies in model systems, it was proposed that molecular abnormalities within the ovaries or a diminished primordial follicle pool cause FXDOR/FXPOI. To elucidate the defects instigating FXDOR/FXPOI, we examined human oocytes obtained from PM carriers undergoing in vitro fertilization (IVF). We found that the number of MII oocytes was reduced suggesting that the maturation of the oocytes is constrained in PM carriers. Furthermore, immature PM oocytes contained abnormal inclusions, irregular ubiquitin levels and DNA breaks. Despite these defects PM oocytes passed the DNA damage checkpoints. However, in anaphase I PM oocytes failed to initiate the protrusion of the first polar body. In addition, these oocytes amassed bundle actin structures, lacked an actin cap and had elevated profilin1 level. Profilin1 limits the formation of branched actin structures which are necessary for actin cap formation and membrane protrusions. Surprisingly, our results suggest that in PM oocytes an increase in FMRP elevates the profilin1 translation, which leads to the cytoskeleton defects and deficiencies in formation of the first polar body. We also analyzed the decline of MII oocytes in aging human ovaries. Similar, we found that the profilin1 expression and formation of the actin cytoskeleton were dysregulated due to appearance of cytoplasmatic FMRP foci in aged human oocytes. Thus, these results reveal that defects during anaphase I hinder the maturation of human oocytes resulting in FXDOR/FXPOI in PM carriers and a reduction in mature oocytes in women with advanced maternal age.

DOI: https://doi.org/10.1101/2025.02.23.639319
iScience. 2025 Mar 21. 28(3): 111977

Generation of primordial germ cell-like cells by two germ plasm components, dnd1 and nanos3, in medaka (Oryzias latipes).

Toshiya Nishimura, Takafumi Fujimoto.

  In teleost fish, primordial germ cells (PGCs), the precursors of eggs and sperm, develop from cells that inherit maternal germ plasm (GP). Although numerous GP component genes have been identified, the minimum set of genes essential for germline formation remains unknown. Herein, we provide evidence that dnd1 and nanos3 synergistically induce PGC-like cells from the blastomeres of medaka embryos. One-cell stage embryos injected with dnd1 and nanos3 mRNA (DN-OE) showed developmental arrest before gastrulation and upregulation of PGC markers. Transplantation experiments revealed that most transplanted DN-OE blastomeres migrated into the gonadal ridge of host embryos, resulting in the production of functional eggs and sperm. Furthermore, the combination of genome editing and PGC induction techniques successfully generated transgenic knock-in medaka, demonstrating enhanced, precise, and stable gene integration. Identifying essential GP genes for PGC formation advances our understanding of germ cell development mechanisms and their biotechnological applications.

Keywords:  Developmental biology; Developmental genetics; Genetics; Genomics; Molecular genetics; Zoology

DOI:  https://doi.org/10.1016/j.isci.2025.111977
Nat Commun. 2025 Mar 13. 16(1): 2516

Overlapping and separable activities of BRA-2 and HIM-17 promote occurrence and regulation of pairing and synapsis during Caenorhabditis elegans meiosis.

Jitka Blazickova, Shalini Trivedi, Richard Bowman, Sowmya Sivakumar Geetha, Silma Subah, Michelle Scuzzarella, Alexander Chang, Uma R Chandran, Judith L Yanowitz, Sarit Smolikove, Verena Jantsch, Monique Zetka, Nicola Silva.

Faithful meiotic segregation requires pairwise alignment of the homologous chromosomes and their synaptonemal complex (SC) mediated stabilization. Here, we investigate factors that promote and coordinate these events during C. elegans meiosis. We identify BRA-2 (BMP Receptor Associated family member 2) as an interactor of HIM-17, previously shown to promote double-strand break formation. We found that loss of bra-2 impairs synapsis elongation without affecting homolog recognition, chromosome movement or SC maintenance. Epistasis analyses reveal previously unrecognized activities for HIM-17 in regulating homolog pairing and SC assembly in a partially overlapping manner with BRA-2. We show that removing bra-2 or him-17 restores nuclear clustering, recruitment of PLK-2 at the nuclear periphery, and abrogation of ectopic synapsis in htp-1 mutants, suggesting intact CHK-2-mediated signaling and presence of a barrier that prevents SC polymerization in the absence of homology. Our findings shed light on the regulatory mechanisms ensuring faithful pairing and synapsis.

DOI: https://doi.org/10.1038/s41467-025-57862-y
Development. 2025 Mar 10. pii: dev.204585. [Epub ahead of print]

FG repeats drive co-clustering of nuclear pores and P granules in the C. elegans germline.

Laura L Thomas, Devavrat M Bodas, Geraldine C Seydoux.

  Condensates that accumulate small RNA biogenesis factors (nuage) are common in germ cells and often associate with nuclei. In the C. elegans germline, P granules overlay large clusters of nuclear pores and this organization has been proposed to facilitate surveillance of nascent transcripts by Argonaute proteins enriched in P granules. We report that co-clustering of nuclear pores and P granules depends on FG repeat containing nucleoporins and FG repeats in the Vasa class helicase GLH-1. Mutants that prevent co-clustering are fertile under standard growth conditions and only mis-regulate a minority of genes, including replication-dependent histones. Our observations suggest that association with nuclear pores, while non-essential for genome surveillance, may serve to tune mRNA flow through P granules and other nuage condensates.

Keywords:   C. elegans ; Germ granule; Histone; Nuclear pore; P granule

DOI:  https://doi.org/10.1242/dev.204585
J Ovarian Res. 2025 Mar 12. 18(1): 53

Follicular metabolic dysfunction, oocyte aneuploidy and ovarian aging: a review.

Die Wu, Chuanming Liu, Lijun Ding.

  With the development of modern society and prolonged education, more women choose to delay their childbearing age, which greatly increases the number of women aged older than 35 years with childbearing needs. However, with increasing age, the quantity and quality of oocytes continue to fall, especially with increasing aneuploidy, which leads to a low in vitro fertilization (IVF) success rate, high abortion rate and high teratogenesis rate in assisted reproduction in women with advanced maternal age. In addition to genetics and epigenetics, follicular metabolism homeostasis is closely related to ovarian aging and oocyte aneuploidy. Glucose, lipid, and amino acid metabolism not only provide energy for follicle genesis but also regulate oocyte development and maturation. This review focuses on the relationships among follicular metabolism, oocyte aneuploidy, and ovarian aging and discusses potential therapeutic metabolites for ovarian aging.

Keywords:  DNA repair; Epigenetics; Genetics; Infertility; Meiotic defects; Metabolism; Mitochondrial quality; Ovarian aging

DOI:  https://doi.org/10.1186/s13048-025-01633-2
Elife. 2025 Mar 10. pii: RP100730. [Epub ahead of print]13

The asymmetric expression of HSPA2 in blastomeres governs the first embryonic cell-fate decision.

Jiayin Gao, Jiawei Wang, Shiyu Liu, Jinzhu Song, Chuanxin Zhang, Boyang Liu, Keliang Wu.

  The first cell-fate decision is the process by which cells of an embryo take on distinct lineage identities for the first time, thus representing the beginning of developmental patterning. Here, we demonstrate that the molecular chaperone heat shock protein A2 (HSPA2), a member of the 70 kDa heat shock protein (HSP70) family, is asymmetrically expressed in the late 2-cell stage of mouse embryos. The knockdown of Hspa2 in one of the 2-cell blastomeres prevented its progeny predominantly towards the inner cell mass (ICM) fate. In contrast, the overexpression of Hspa2 in one of the 2-cell blastomeres did not induce the blastomere to differentiate towards the ICM fate. Furthermore, we demonstrated that HSPA2 interacted with CARM1 and its levels correlated with ICM-associated genes. Collectively, our results identify HSPA2 as a critical early regulator of the first cell-fate decision in mammalian 2-cell embryos.

Keywords:  CARM1; HSPA2; developmental biology; embryo; first cell-fate decision; inner cell mass; mouse

DOI:  https://doi.org/10.7554/eLife.100730
Development. 2025 Mar 11. pii: dev.204618. [Epub ahead of print]

Inhibition of HDAC4 in granulosa cells improved co-cultured oocyte maturation in vitro independent of LH in porcine.

Zhenzi Zuo, Yibing Bao, Lin Lin, Hengxing Li, Tengteng Wang, Guoliang Xia, Chao Wang.

  In domestic animals, the mechanisms by which the luteinizing hormone (LH) surge induces oocyte meiosis resumption and maturation through follicular somatic cells remain unclear. Given the pivotal roles of histone deacetylases (HDACs) in regulating gametogenesis, this study investigated the roles of HDACs in follicular granulosa cells (GCs) in mediating LH action during oocyte maturation in pigs. The results showed that histone deacetylase 4 (HDAC4) levels in cultured GCs increased in a time-dependent manner with follicle-stimulating hormone (FSH) stimulation but significantly decreased with LH treatment. The LH-induced reduction of HDAC4 was mediated by the accumulation of extracellular signal-regulated kinase 1/2 (ERK1/2), which subsequently increased H3K18 acetylation and promoted the recruitment of SMAD family member 3 (SMAD3) to the promoter of the EGF-like growth factor amphiregulin (Areg). Notably, specific inhibition of HDAC4 promoted oocyte maturation independently of LH in vitro, and the developmental potential of these matured oocytes was comparable to those induced by LH in vitro. In conclusion, HDAC4 in follicular somatic cells serves as a gonadotrophin-responsive epigenetic modification factor that negatively regulates oocyte meiosis resumption in pigs.

Keywords:  AREG; H3K18ac; HDAC4; Porcine oocyte; SMAD3

DOI:  https://doi.org/10.1242/dev.204618
Nat Struct Mol Biol. 2025 Mar 13.

A nuclear pore-anchored condensate enables germ granule organization and transgenerational epigenetic inheritance.

Pu Lu, Boyuan Deng, Xinru Li, Xufang Niu, Yanhong Qiu, Yuntao Liang, Yonglin Liang, Guorun Tang, Zhongping Yuan, Guanzheng Luo, Scott Kennedy, Gang Wan.

Biomolecular condensates, such as stress and germ granules, often contain subcompartments. For instance, the Caenorhabditis elegans germ granule, which localizes near the outer nuclear membrane of germ cell nuclei, is composed of at least four ordered compartments, each housing distinct sets of proteins and RNAs. How these compartments form and why they are spatially ordered remains poorly understood. Here, we show that the conserved DEAD-box RNA helicase DDX-19 defines another compartment of the larger C. elegans germ granule, which we term the D compartment. The D compartment exhibits properties of a liquid condensate and forms between the outer nuclear pore filament and other compartments of the germ granule. Two nuclear pore proteins, NPP-14 and GLEL-1, are required for its formation, suggesting that the D compartment localizes adjacent to the outer nuclear membrane through interactions with the nuclear pore. The loss of DDX-19, NPP-14 or GLEL-1 leads to functional defects, including aberrant formation of the other four germ granule compartments, a loss of germline immortality and dysregulation of small RNA-based transgenerational epigenetic inheritance programs. Hence, we propose that a function of the D compartment is to anchor larger germ granules to nuclear pores, enabling germ granule compartmentalization and promoting transgenerational RNA surveillance.

DOI: https://doi.org/10.1038/s41594-025-01515-7
bioRxiv. 2025 Feb 25. pii: 2025.02.24.639895. [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 asyn-chronous 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 bifurcations in mouse development.

DOI: https://doi.org/10.1101/2025.02.24.639895
bioRxiv. 2025 Feb 27. pii: 2025.02.27.640568. [Epub ahead of print]

Geometric, cell cycle and maternal-to-zygotic transition-associated YAP dynamics during preimplantation embryo development.

Madeleine Chalifoux, Maria Avdeeva, Eszter Posfai.

  During the first cell fate decision in mammalian embryos the inner cell mass cells, which will give rise to the embryo proper and other extraembryonic tissues, segregate from the trophectoderm cells, the precursors of the placenta. Cell fate segregation proceeds in a gradual manner encompassing two rounds of cell division, as well as cell positional and morphological changes. While it is known that the activity of the Hippo signaling pathway and the subcellular localization of its downstream effector YAP dictate lineage specific gene expression, the response of YAP to these dynamic cellular changes remains incompletely understood. Here we address these questions by quantitative live imaging of endogenously tagged YAP while simultaneously monitoring geometric cellular features and cell cycle progression throughout cell fate segregation. We apply a probabilistic model to our dynamic data, providing a quantitative characterization of the mutual effects of YAP and cellular relative exposed area, which has previously been shown to correlate with subcellular YAP localization in fixed samples. Additionally, we study how nuclear YAP levels are influenced by other factors, such as the decreasing pool of maternally provided YAP that is partitioned to daughter cells through cleavage divisions, cell cycle-associated nuclear volume changes, and a delay after divisions in adjusting YAP levels to new cell positions. Interestingly, we find that establishing low nuclear YAP levels required for the inner cell mass fate is largely achieved by passive cell cycle-associated mechanisms. Moreover, contrary to expectations, we find that mechanical perturbations that result in cell shape changes do not influence YAP localization in the embryo. Together our work identifies how various inputs are integrated over a dynamic developmental time course to shape the levels of a key molecular determinant of the first cell fate choice.

Keywords:  YAP; cell fate; dynamic Bayesian networks; live imaging; mouse; preimplantation

DOI:  https://doi.org/10.1101/2025.02.27.640568
bioRxiv. 2025 Feb 25. pii: 2025.02.21.639591. [Epub ahead of print]

Hyper-ovulation in an ovarian-specific transgenic mouse model.

Luis C Muñiz, James Reilly, Melissa Spigelman, Carlos A Molina.

Ovulation is a fundamental prerequisite for achieving successful reproduction. In vertebrates, ovulation is controlled by the cyclical action of hormones, particularly the gonadotropins such as follicle stimulating hormone (FSH) and luteinizing hormone (LH). A critical component of the intracellular activity of these two hormones is relayed by the second messenger cAMP. Although it is well established that a family of transcription factors facilitate cAMP mediated gene expression, it remains unknown how these factors directly affect ovulation. In particular, the Inducible cAMP Early Repressor (ICER) has been implicated in the transcriptional repression of FSH inducible genes during folliculogenesis. Here we show, using an ovarian-specific transgenic mouse model that ICER potentiates ovulation. We observed a twofold rate increase in ovulation for transgenic mice when compared to the wild type in response to exogenous gonadotropin treatment. Furthermore, mature cycling transgenic mice display a significantly enhanced ovulation rate compared to the wild-type. The observed changes in ovulation in the transgenic females are accompanied by altered gonadotropins production and gene expression. Most significantly, the expression of inhibin alpha subunit (INHA) was found to be about 5-fold higher in the transgenic mice. These observations may aid in unraveling some of the molecular mechanisms underlying ovulation and be relevant to the development of novel reproductive technologies.
Summary Sentence: Generation of an FSH inducible ovarian specific FLAG-ICER-II© Tg Mice results in hyper-ovulation upon gonadotropin stimulation.

DOI: https://doi.org/10.1101/2025.02.21.639591
Curr Opin Cell Biol. 2025 Mar 07. pii: S0955-0674(25)00029-8. [Epub ahead of print]94 102491

Multifaceted regulation of asymmetric cell division by the actin cytoskeleton.

Peishan Yi, Guangshuo Ou, Wei Li.

Asymmetric cell division (ACD) is essential for generating cell diversity in multicellular eukaryotes, yet the underlying mechanisms remain largely unresolved. Well-established models of ACD, such as microtubule-based spindle displacement in Caenorhabditis elegans embryos and preprophase band assembly in plants provide valuable insights but fail to fully explain asymmetry establishment in others. In this article, we discuss how actin-dependent mechanisms govern ACD in model systems, highlighting emerging commonalities and differences. Given its broad impact, the actin cytoskeleton may play a more significant role in ACD than currently recognized, serving as a fundamental component during organismal development across kingdoms.

DOI: https://doi.org/10.1016/j.ceb.2025.102491