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Article
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A conserved NR5A1-responsive enhancer regulates SRY in testis-determination
Disease-causing variants define a conserved and unique NR5A1 responsive enhancer for SRY expression to initiate testis-determination in humans. Modelling regulatory variants causing sex-reversal provides a tool to understand global enhancer activity.
- Denis Houzelstein
- , Caroline Eozenou
- & Ken McElreavey
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Article
| Open Access
p53 regulates diverse tissue-specific outcomes to endogenous DNA damage in mice
DNA repair deficiency can cause tissue-specific phenotypes in humans and mice. Here, the authors find that p53 drives different, but tissue-specific responses despite the same defect in DNA repair. p53 drives blood stem cell loss but restrains liver polyploidisation in the absence of Ercc1.
- Ross J. Hill
- , Nazareno Bona
- & Gerry P. Crossan
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Article
| Open Access
JAK-STAT-dependent contact between follicle cells and the oocyte controls Drosophila anterior-posterior polarity and germline development
The authors identified a cell population in Drosophila follicles that elaborate filopodia penetrating the oocyte they are contacting. These somatic cells are essential during oogenesis to regulate polarity and germline development of the future embryo.
- Charlotte Mallart
- , Sophie Netter
- & Marianne Malartre
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Article
| Open Access
Nutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control
The quality of germline mitochondria is essential for producing healthy oocytes. Here, Ng, Chan and Pek report a stable intron that modulates germline mitochondrial quality control during fasting, heat stress and aging.
- Annabel Qi En Ng
- , Seow Neng Chan
- & Jun Wei Pek
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Article
| Open Access
Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation
The activity of Drosophila male germline stem cells is tightly regulated by a cluster of somatic niche cells. Here they find that Dpp induces opposed cellular responses in stem cells versus in differentiating descendants, thereby ensuring spatial control of the niche with a single factor.
- Sharif M. Ridwan
- , Autumn Twillie
- & Mayu Inaba
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Article
| Open Access
HRDE-2 drives small RNA specificity for the nuclear Argonaute protein HRDE-1
Argonaute proteins are loaded with small RNAs to confer target RNA specificity and proper gene silencing. Here, the authors establish that HRDE-2 recruits the unloaded nuclear Argonaute HRDE-1 to germ granules to facilitate correct small RNA loading.
- Shihui Chen
- & Carolyn M. Phillips
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Article
| Open Access
RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis
Gene expression dynamics are tightly regulated during spermatogenesis, with disruptions resulting in infertility. Here they identify a critical role for RNA PolII pausing in spermatogenesis and show that loss of the RNA PolII pausing factor NELF causes meiotic arrest.
- Emily G. Kaye
- , Kavyashree Basavaraju
- & Prabhakara P. Reddi
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Article
| Open Access
Derivation of human primordial germ cell-like cells in an embryonic-like culture
Derivation of human primordial germ cell-like cells (hPGCLCs) is critical for reproductive medicine. Here, authors report the induction of hPGCLCs in a bioengineered human pluripotent stem cell culture that mimics peri-implantation human development.
- Sajedeh Nasr Esfahani
- , Yi Zheng
- & Jianping Fu
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Article
| Open Access
The evolution of centriole degradation in mouse sperm
Centrioles have a conserved structure and function but have diversified in sperm. Here the authors provide insight into the molecular mechanisms and adaptive evolution underlying this diversification.
- Sushil Khanal
- , Ankit Jaiswal
- & Tomer Avidor-Reiss
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Article
| Open Access
STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation
The sperm flagellum is composed of tubulin-based microtubules and is critical for sperm motility and thus male fertility. Here, the authors show that STYXL1 regulates CCT complex-facilitated tubulin folding and is essential for sperm flagella formation.
- Yu Chen
- , Mengjiao Luo
- & Xuejiang Guo
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Article
| Open Access
Maternal vitamin B1 is a determinant for the fate of primordial follicle formation in offspring
The authors show that maternal high-fat diet influences offspring’s ovarian reserve through maternal-embryonic cross-talk in mice and that maternal vitamin B1 supplementation could rescue ovarian primordial follicle reserve in mouse offspring.
- Wen-Xiang Liu
- , Hai-Ning Liu
- & Teng Zhang
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Article
| Open Access
STRA8–RB interaction is required for timely entry of meiosis in mouse female germ cells
Female germ cells initiate meiosis within a limited time period in the fetal ovary. Here the authors show that the interaction between STRA8 and RB ensures precise timing of meiosis initiation and highlight the regulatory mechanisms underlying female-specific meiotic initiation in mice.
- Ryuki Shimada
- , Yuzuru Kato
- & Kei-ichiro Ishiguro
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Article
| Open Access
Metabolic regulation of proteome stability via N-terminal acetylation controls male germline stem cell differentiation and reproduction
How cellular metabolism is connected to differentiation remains poorly understood. Here the authors report a regulatory cascade in which circulating citrate regulates sperm production by controlling protein stability via a specific protein post-translational modification.
- Charlotte M. François
- , Thomas Pihl
- & Bruno Hudry
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Article
| Open Access
ALKBH5 controls the meiosis-coupled mRNA clearance in oocytes by removing the N 6-methyladenosine methylation
N6-methyladenosine (m6A) maintains maternal RNA stability in oocytes. Here, the authors identify demethylase ALKBH5 as a key determinant of oocyte quality and unveil the facilitating role of ALKBH5-mediated m6A removal in maternal RNA decay.
- Long Bai
- , Yu Xiang
- & Yimin Zhu
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Article
| Open Access
C. elegans germ granules sculpt both germline and somatic RNAome
Germ granules are membraneless organelles that act as organizing centers for small RNA biogenesis during germline development. Here they show the LOTUS domain protein eggd-1 organizes germ granules, and reveal a germ line-to-soma communication pathway activated upon perturbation of germ granules.
- Ian F. Price
- , Jillian A. Wagner
- & Wen Tang
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Article
| Open Access
The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters
The role of PIWI proteins in mammalian reproduction remains poorly understood. Here, using golden hamsters, the authors establish expression profiles for all four PIWIs during gametogenesis and characterize their associated reproductive defects.
- Xiaolong Lv
- , Wen Xiao
- & Ligang Wu
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Article
| Open Access
SYPL1 defines a vesicular pathway essential for sperm cytoplasmic droplet formation and male fertility
The cytoplasmic droplet is an elusive structure of mammalian sperm. Here, the authors uncover a key gene that defines a vesicular pathway essential for cytoplasmic droplet formation and male fertility.
- Jiali Liu
- , Louis Hermo
- & Chen Chen
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Article
| Open Access
Biophysical ordering transitions underlie genome 3D re-organization during cricket spermiogenesis
Orsi et al. identify an elegant solution to DNA packing in cricket sperm nuclei, whereby relatively simple biophysical changes in chromatin properties result in a liquid crystal-like twisted spool organization that favors ultracompaction.
- Guillermo A. Orsi
- , Maxime M. C. Tortora
- & Benjamin Loppin
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Article
| Open Access
Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice
Generation of mature oocytes requires tight regulation of a discontinuous meiotic cell cycle. Here they show that the acetyltransferase Nat10 mediates modification of RNAs targeted for degradation and find that this process is essential for female oocyte meiosis and maturation.
- Xue Jiang
- , Yu Cheng
- & Jianqiang Bao
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Article
| Open Access
Divergent molecular signatures in fish Bouncer proteins define cross-fertilization boundaries
The egg membrane protein Bouncer is an important mediator of gamete interaction and prevents cross-fertilisation between medaka and zebrafish. This study demonstrates unique functional and structural differences in Bouncer proteins of these and other distantly related fish species which may determine which species can hybridize.
- Krista R. B. Gert
- , Karin Panser
- & Andrea Pauli
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Article
| Open Access
Higher-order epistasis shapes natural variation in germ stem cell niche activity
Stem cell niches regulate proliferation of stem cells, but variation in this control across natural populations has not been explored. Here they combine quantitative genetics and gene editing to show that natural variation in C. elegans germ stem cell niche activity is shaped by complex gene-gene interactions.
- Sarah R. Fausett
- , Asma Sandjak
- & Christian Braendle
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Article
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Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility
Testis-specific serine/threonine kinases have been associated with male infertility, but the mechanism for this connection is unclear. Here they identify a Drosophila homolog, dTSSK, which is essential for male fertility in fruit flies and has functionally conserved catalytic activity with human TSSKs.
- Xuedi Zhang
- , Ju Peng
- & Guanjun Gao
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Article
| Open Access
Single-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis
Germ cells undergo dramatic chromatin and transcriptomic changes during spermatogenesis, though how this is controlled is not well established. Here they show that RNA-binding protein DDX43 directs the spermatid differentiation trajectory and regulates chromatin remodeling in spermiogenesis, which is partially mediated by its target gene Elfn2.
- Huanhuan Tan
- , Weixu Wang
- & Ke Zheng
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Article
| Open Access
A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility
Mammalian sperm need to be matured in the epididymis to achieve potential for fertility. Here the authors identify NICOL as a secreted protein that acts on the epididymis to trigger its functional differentiation and induce sperm maturation.
- Daiji Kiyozumi
- , Kentaro Shimada
- & Masahito Ikawa
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Article
| Open Access
DNMT1 mutant ants develop normally but have disrupted oogenesis
The role of DNA methylation in insects is poorly understood. Here, the authors knock out the DNA methyltransferase DNMT1 in an ant and find no obvious effects on development, rather showing that this enzyme seems to play a crucial role during early oogenesis.
- Iryna Ivasyk
- , Leonora Olivos-Cisneros
- & Daniel J. C. Kronauer
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Article
| Open Access
ARRDC5 expression is conserved in mammalian testes and required for normal sperm morphogenesis
Male organisms produce huge numbers of sperm each day, with defects in the process resulting infertility. Here they show that arrestin domain-containing 5 (ARRDC5) is a testis-specific molecule required for mammalian spermatogenesis.
- Mariana I. Giassetti
- , Deqiang Miao
- & Jon M. Oatley
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Perspective
| Open Access
Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development
Increasing evidence suggests parental environmental stressors can influence offspring health and disease outcomes. In this perspective, the authors provide an update of the paternal epigenetic inheritance field and propose links between paternally transmitted epigenetic influences and functional changes to the embryo.
- Ariane Lismer
- & Sarah Kimmins
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Article
| Open Access
A-MYB and BRDT-dependent RNA Polymerase II pause release orchestrates transcriptional regulation in mammalian meiosis
During spermatogenic meiosis, chromatin changes due to transcription, homologous recombination, and chromosome synapsis must be coordinated. Here they show that A-MYC and BRDT regulate release of paused RNA PolII to induce a transcriptional burst during pachytene of prophase I.
- Adriana K. Alexander
- , Edward J. Rice
- & Charles G. Danko
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Article
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Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity
Male meiosis relies on canonical centrosomes for spindle formation, but how this differs from acentrosomal oocyte meiosis is unclear. Here they show that spindle formation in sperm relies on DYNLRB2, similar to the activity of DYNLRB1 in mitotic cells.
- Shuwen He
- , John P. Gillies
- & Hiroki Shibuya
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Article
| Open Access
The m6A reader PRRC2A is essential for meiosis I completion during spermatogenesis
Modification of RNA with m6A has been shown to be important during spermatogenesis. Here they identify post-transcriptional functions of PRRC2A, showing it promotes transcriptome transition from spermatogonia to spermatocytes and the translation of genes related to cell division.
- Xinshui Tan
- , Caihong Zheng
- & Fengchao Wang
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Article
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CENP-F-dependent DRP1 function regulates APC/C activity during oocyte meiosis I
Spindle assembly checkpoint controls anaphase onset and guarantees appropriate chromosome segregation. Here, the authors report that dynamin-related protein 1 is recruited to kinetochores by CENP-F to regulate metaphase-to-anaphase transition by controlling APC/C activity in mouse oocyte meiosis
- Cheng-Jie Zhou
- , Xing-Yue Wang
- & Cheng-Guang Liang
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Article
| Open Access
Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation
Here the authors show that active DNA damage response signaling is required both to initiate and maintain meiotic sex chromosome inactivation via a dynamic and reversible process.
- Hironori Abe
- , Yu-Han Yeh
- & Satoshi H. Namekawa
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Article
| Open Access
TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks
TOPOVIBL and REC114 are required for meiotic DNA double-strand breaks (DSBs). This study shows that TOPOVIBL forms a complex with REC114 and mice carrying mutations that disrupt the interaction show DSB defects with distinct outcomes in males and females.
- Alexandre Nore
- , Ariadna B. Juarez-Martinez
- & Bernard de Massy
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Article
| Open Access
Eya-controlled affinity between cell lineages drives tissue self-organization during Drosophila oogenesis
Oogenesis depends on close interaction between germ cells and the surrounding somatic niche. Here the authors demonstrate that Eya controls bilateral affinity at the germline-soma interface to generate self-organizing inter-lineage units that ensure oocyte maturation.
- Vanessa Weichselberger
- , Patrick Dondl
- & Anne-Kathrin Classen
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Article
| Open Access
BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency
Primary ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction that results in infertility. Here they show that BCN1 mutation results in premature ovarian follicle activation and atresia through dysregulation of ferroptosis.
- Feixia Wang
- , Yifeng Liu
- & Dan Zhang
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Article
| Open Access
Single-cell transcriptome and translatome dual-omics reveals potential mechanisms of human oocyte maturation
Development of methods for simultaneous single cell analysis of transcription and translation is still underway. Here, Hu et al. develop single-cell transcriptome and translatome dual-omics on human oocytes, which enables them to identify OOSP2 as an induction factor during human oocyte maturation.
- Wenqi Hu
- , Haitao Zeng
- & Kehkooi Kee
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Article
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Cytoplasmic forces functionally reorganize nuclear condensates in oocytes
Cytoskeletal activity generates mechanical forces known to agitate and displace membrane-bound organelles in the cytoplasm. In oocytes, Al Jord et al. discover that these cytoplasmic forces functionally remodel nuclear RNA-processing condensates across scales for developmental success.
- Adel Al Jord
- , Gaëlle Letort
- & Marie-Hélène Verlhac
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Article
| Open Access
PRC1-mediated epigenetic programming is required to generate the ovarian reserve
In humans, the ovarian reserve is maintained over decades by meiotic arrest of oocytes. Here the authors show that Polycomb Repressive Complex 1 (PRC1)-mediated epigenetic programming is essential for formation of ovarian reserve and thus female reproductive lifespan.
- Mengwen Hu
- , Yu-Han Yeh
- & Satoshi H. Namekawa
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Article
| Open Access
Histone H3K36me2 and H3K36me3 form a chromatin platform essential for DNMT3A-dependent DNA methylation in mouse oocytes
DNMT3A is known to methylate DNA at histone H3 lysine 36 (H3K36me3)-marked transcriptionally active regions in mouse oocytes. Here the authors show that DNMT3A is also guided by H3K36me2 to methylate broad domains in genic and intergenic loci, as well as on the X chromosome. These two histone marks together comprise the minimal chromatin signature for global DNA methylation in mouse oocytes.
- Seiichi Yano
- , Takashi Ishiuchi
- & Hiroyuki Sasaki
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Article
| Open Access
Highly conserved shifts in ubiquitin-proteasome system (UPS) activity drive mitochondrial remodeling during quiescence
Dynamic regulation of cellular proteostasis is linked to the metabolic state of quiescent cells in vivo. Here, the authors show, in multiple organisms, that shifts in the ubiquitin-proteome system are coupled to mitochondrial metabolic changes and subsequent respiratory quiescence.
- Sibiao Yue
- , Lei Wang
- & Matthew H. Sieber
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Article
| Open Access
Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing
The regulatory mechanisms contributing to male reproductive ageing are unknown. Here, the authors show that Nestin-dependent mito-ER contacts (MERCs) regulate stem Leydig cell (SLC) senescence and provide insights into SLCs-targeting therapies.
- Senyu Yao
- , Xiaoyue Wei
- & Jiancheng Wang
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Article
| Open Access
hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells
Coordinated regulation of alternative splicing is essential for germ cell development. Here, the authors report that hnRNPH1 interacts with alternative splicing factors PTBP2 and SRSF3 in the germline to regulate pre-mRNA alternative splicing.
- Shenglei Feng
- , Jinmei Li
- & Shuiqiao Yuan
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Article
| Open Access
Dynamic mRNA degradome analyses indicate a role of histone H3K4 trimethylation in association with meiosis-coupled mRNA decay in oocyte aging
Developmental potential of oocytes decreases in women of advanced age. Here the authors observe impaired meiosis-coupled mRNA decay and reduced CXXC1-maintained histone H3K4 trimethylation in old oocytes of mouse and humans.
- Yun-Wen Wu
- , Sen Li
- & Qian-Qian Sha
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Article
| Open Access
BMP4 drives primed to naïve transition through PGC-like state
Multiple pluripotent states have been described in mouse and human stem cells. Here the authors describe trajectories during BMP4 induced primed to naïve transition, which bifurcates into naïve and trophoblast-like branches with a PGC-like intermediate at the naïve branch.
- Shengyong Yu
- , Chunhua Zhou
- & Jing Liu
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Article
| Open Access
3D chromatin remodelling in the germ line modulates genome evolutionary plasticity
The role of genome folding in the heritability and evolvability of structural variations is not well understood. Here the authors investigate the impact of the three-dimensional genome topology of germ cells in the formation and transmission of gross structural genomic changes detected from comparing whole-genome sequences of 14 rodent species.
- Lucía Álvarez-González
- , Frances Burden
- & Aurora Ruiz-Herrera
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Article
| Open Access
Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles
CRISPR gene drives are genetic elements capable of quickly spreading through populations and they offer promising solutions for curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations. Here the authors present a method for overcoming resistance alleles “double-tap,” that encodes additional gRNAs in the gene drive that target the most common generated resistance alleles.
- Alena L. Bishop
- , Víctor López Del Amo
- & Valentino M. Gantz
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Article
| Open Access
Distinctive molecular features of regenerative stem cells in the damaged male germline
Male germline regeneration after damage is dependent on spermatogonial stem cells (SSCs) but pathways mediating the regenerative response are unclear. Here the authors define roles for growth factor signalling and mTORC1 in SSC-driven regeneration.
- Hue M. La
- , Jinyue Liao
- & Robin M. Hobbs
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Article
| Open Access
Epigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice
Here the authors show that a high-fat diet in pregnant mice can release silencing of the imprinted Dlk1 locus in multiple generations of offspring. They found that this occurs via changes in microRNA expression at the locus of interest, as well as transcriptional changes across the genome, in the developing oocytes.
- Mathew Van de Pette
- , Andrew Dimond
- & Amanda G. Fisher
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Article
| Open Access
CEP128 is involved in spermatogenesis in humans and mice
CEP128 is a centrosomal protein important for the organization of centriolar microtubules. Here, the authors show that a CEP128 variant observed in human male siblings causes reduced sperm counts and morphologically abnormal sperm when modeled in mice, suggesting a role for CEP128 in male fertility.
- Xueguang Zhang
- , Lingbo Wang
- & Ying Shen
Combined and differential roles of ADD domains of DNMT3A and DNMT3L on DNA methylation landscapes in mouse germ cells