RESUMO
Following the fertilization of an egg by a single sperm, the egg coat or zona pellucida (ZP) hardens and polyspermy is irreversibly blocked. These events are associated with the cleavage of the N-terminal region (NTR) of glycoprotein ZP2, a major subunit of ZP filaments. ZP2 processing is thought to inactivate sperm binding to the ZP, but its molecular consequences and connection with ZP hardening are unknown. Biochemical and structural studies show that cleavage of ZP2 triggers its oligomerization. Moreover, the structure of a native vertebrate egg coat filament, combined with AlphaFold predictions of human ZP polymers, reveals that two protofilaments consisting of type I (ZP3) and type II (ZP1/ZP2/ZP4) components interlock into a left-handed double helix from which the NTRs of type II subunits protrude. Together, these data suggest that oligomerization of cleaved ZP2 NTRs extensively cross-links ZP filaments, rigidifying the egg coat and making it physically impenetrable to sperm.
Assuntos
Glicoproteínas da Zona Pelúcida , Humanos , Masculino , Sêmen , Espermatozoides/química , Espermatozoides/metabolismo , Zona Pelúcida/química , Zona Pelúcida/metabolismo , Glicoproteínas da Zona Pelúcida/química , Glicoproteínas da Zona Pelúcida/metabolismo , Óvulo/química , Óvulo/metabolismo , FemininoRESUMO
Animal fertilization relies on hundreds of sperm racing toward the egg, whereas, in angiosperms, only two sperm cells are delivered by a pollen tube to the female gametes (egg cell and central cell) for double fertilization. However, unsuccessful fertilization under this one-pollen-tube design can be detrimental to seed production and plant survival. To mitigate this risk, unfertilized-gamete-controlled extra pollen tube entry has been evolved to bring more sperm cells and salvage fertilization. Despite its importance, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we report that, in Arabidopsis, the central cell secretes peptides SALVAGER1 and SALVAGER2 in a directional manner to attract pollen tubes when the synergid-dependent attraction fails or is terminated by pollen tubes carrying infertile sperm cells. Moreover, loss of SALs impairs the fertilization recovery capacity of the ovules. Therefore, this research uncovers a female gamete-attraction system that salvages seed production for reproductive assurance.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Animais , Arabidopsis/fisiologia , Fertilização , Tubo Polínico , Sementes , Células Germinativas VegetaisRESUMO
Most human embryos are aneuploid. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but its origin remains elusive. Human zygotes that cluster their nucleoli at the pronuclear interface are thought to be more likely to develop into healthy euploid embryos. Here, we show that the parental genomes cluster with nucleoli in each pronucleus within human and bovine zygotes, and clustering is required for the reliable unification of the parental genomes after fertilization. During migration of intact pronuclei, the parental genomes polarize toward each other in a process driven by centrosomes, dynein, microtubules, and nuclear pore complexes. The maternal and paternal chromosomes eventually cluster at the pronuclear interface, in direct proximity to each other, yet separated. Parental genome clustering ensures the rapid unification of the parental genomes on nuclear envelope breakdown. However, clustering often fails, leading to chromosome segregation errors and micronuclei, incompatible with healthy embryo development.
Assuntos
Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/genética , Aneuploidia , Animais , Bovinos , Nucléolo Celular/metabolismo , Núcleo Celular/metabolismo , Centrossomo/metabolismo , Segregação de Cromossomos/fisiologia , Cromossomos/metabolismo , Fertilização/genética , Humanos , Masculino , Microtúbulos/metabolismo , Mitose , Oócitos/metabolismo , Espermatozoides/metabolismo , Zigoto/metabolismoRESUMO
The paternal genome undergoes a massive exchange of histone with protamine for compaction into sperm during spermiogenesis. Upon fertilization, this process is potently reversed, which is essential for parental genome reprogramming and subsequent activation; however, it remains poorly understood how this fundamental process is initiated and regulated. Here, we report that the previously characterized splicing kinase SRPK1 initiates this life-beginning event by catalyzing site-specific phosphorylation of protamine, thereby triggering protamine-to-histone exchange in the fertilized oocyte. Interestingly, protamine undergoes a DNA-dependent phase transition to gel-like condensates and SRPK1-mediated phosphorylation likely helps open up such structures to enhance protamine dismissal by nucleoplasmin (NPM2) and enable the recruitment of HIRA for H3.3 deposition. Remarkably, genome-wide assay for transposase-accessible chromatin sequencing (ATAC-seq) analysis reveals that selective chromatin accessibility in both sperm and MII oocytes is largely erased in early pronuclei in a protamine phosphorylation-dependent manner, suggesting that SRPK1-catalyzed phosphorylation initiates a highly synchronized reorganization program in both parental genomes.
Assuntos
Cromatina/metabolismo , Protaminas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Núcleo Celular/metabolismo , Cromatina/fisiologia , Montagem e Desmontagem da Cromatina/genética , Montagem e Desmontagem da Cromatina/fisiologia , Fertilização/genética , Histonas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oócitos/metabolismo , Oócitos/fisiologia , Fosforilação , Protamina Quinase/genética , Protamina Quinase/metabolismo , Protaminas/genética , Proteínas Serina-Treonina Quinases/fisiologia , Splicing de RNA/genética , Splicing de RNA/fisiologia , Espermatozoides/metabolismo , Fatores de Transcrição/metabolismo , Zigoto/metabolismoRESUMO
Fertilization is a multistep process that culminates in the fusion of sperm and egg, thus marking the beginning of a new organism in sexually reproducing species. Despite its importance for reproduction, the molecular mechanisms that regulate this singular event, particularly sperm-egg fusion, have remained mysterious for many decades. Here, we summarize our current molecular understanding of sperm-egg interaction, focusing mainly on mammalian fertilization. Given the fundamental importance of sperm-egg fusion yet the lack of knowledge of this process in vertebrates, we discuss hallmarks and emerging themes of cell fusion by drawing from well-studied examples such as viral entry, placenta formation, and muscle development. We conclude by identifying open questions and exciting avenues for future studies in gamete fusion.
Assuntos
Fertilização , Interações Espermatozoide-Óvulo , Animais , Masculino , Mamíferos , Reprodução , Interações Espermatozoide-Óvulo/fisiologia , Espermatozoides/fisiologiaRESUMO
Recognition between sperm and the egg surface marks the beginning of life in all sexually reproducing organisms. This fundamental biological event depends on the species-specific interaction between rapidly evolving counterpart molecules on the gametes. We report biochemical, crystallographic, and mutational studies of domain repeats 1-3 of invertebrate egg coat protein VERL and their interaction with cognate sperm protein lysin. VERL repeats fold like the functionally essential N-terminal repeat of mammalian sperm receptor ZP2, whose structure is also described here. Whereas sequence-divergent repeat 1 does not bind lysin, repeat 3 binds it non-species specifically via a high-affinity, largely hydrophobic interface. Due to its intermediate binding affinity, repeat 2 selectively interacts with lysin from the same species. Exposure of a highly positively charged surface of VERL-bound lysin suggests that complex formation both disrupts the organization of egg coat filaments and triggers their electrostatic repulsion, thereby opening a hole for sperm penetration and fusion.
Assuntos
Fertilização , Invertebrados/fisiologia , Vertebrados/fisiologia , Sequência de Aminoácidos , Animais , Evolução Biológica , Proteínas do Ovo/química , Proteínas do Ovo/metabolismo , Humanos , Invertebrados/química , Invertebrados/genética , Masculino , Modelos Moleculares , Mucoproteínas/química , Mucoproteínas/metabolismo , Óvulo/química , Óvulo/metabolismo , Alinhamento de Sequência , Especificidade da Espécie , Espermatozoides/química , Espermatozoides/metabolismo , Vertebrados/genética , Difração de Raios X , Glicoproteínas da Zona Pelúcida/química , Glicoproteínas da Zona Pelúcida/metabolismoRESUMO
The epigenetic information present in mammalian gametes and whether it is transmitted to the progeny are relatively unknown. We find that many promoters in mouse sperm are occupied by RNA polymerase II (Pol II) and Mediator. The same promoters are accessible in GV and MII oocytes and preimplantation embryos. Sperm distal ATAC-seq sites containing motifs for various transcription factors are conserved in monkeys and humans. ChIP-seq analyses confirm that Foxa1, ERα, and AR occupy distal enhancers in sperm. Accessible sperm enhancers containing H3.3 and H2A.Z are also accessible in oocytes and preimplantation embryos. Furthermore, their interactions with promoters in the gametes persist during early development. Sperm- or oocyte-specific interactions mediated by CTCF and cohesin are only present in the paternal or maternal chromosomes, respectively, in the zygote and 2-cell stages. These interactions converge in both chromosomes by the 8-cell stage. Thus, mammalian gametes contain complex patterns of 3D interactions that can be transmitted to the zygote after fertilization.
Assuntos
Fator de Ligação a CCCTC/genética , Fator 3-beta Nuclear de Hepatócito/genética , Oócitos/metabolismo , Espermatozoides/metabolismo , Zigoto/metabolismo , Animais , Sequência de Bases , Fator de Ligação a CCCTC/metabolismo , Cromatina/química , Cromatina/metabolismo , Sequência Conservada , Embrião de Mamíferos , Desenvolvimento Embrionário/genética , Elementos Facilitadores Genéticos , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Fator 3-beta Nuclear de Hepatócito/metabolismo , Humanos , Macaca mulatta , Masculino , Camundongos , Oócitos/citologia , Oócitos/crescimento & desenvolvimento , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Homologia de Sequência do Ácido Nucleico , Espermatozoides/citologia , Espermatozoides/crescimento & desenvolvimento , Dedos de Zinco/genética , Zigoto/citologia , Zigoto/crescimento & desenvolvimentoRESUMO
The Toarcian Oceanic Anoxic Event (T-OAE; ~183 Mya) was a globally significant carbon-cycle perturbation linked to widespread deposition of organic-rich sediments, massive volcanic CO2 release, marine faunal extinction, sea-level rise, a crisis in carbonate production related to ocean acidification, and elevated seawater temperatures. Despite recognition of the T-OAE as a potential analog for future ocean deoxygenation, current knowledge on the severity of global ocean anoxia is limited largely to studies of the trace element and isotopic composition of black shales, which are commonly affected by local processes. Here, we present the first carbonate-based uranium isotope (δ238U) record of the T-OAE from open marine platform limestones of the southeastern Tethys Ocean as a proxy for global seawater redox conditions. A significant negative δ238U excursion (~0.4) is recorded just prior to the onset of the negative carbon isotope excursion comprised within the T-OAE, followed by a long-lived recovery of δ238U values, thus confirming that the T-OAE represents a global expansion of marine anoxia. Using a Bayesian inverse isotopic mass balance model, we estimate that anoxic waters covered ~6 to 8% of the global seafloor during the peak of the T-OAE, which represents 28 to 38 times the extent of anoxia in the modern ocean. These data, combined with δ238U-based estimates of seafloor anoxic area for other CO2-driven Phanerozoic OAEs, suggest a common response of ocean anoxia to carbon release, thus improving prediction of future anthropogenically induced ocean deoxygenation.
RESUMO
Extending and safeguarding tropical forest ecosystems is critical for combating climate change and biodiversity loss. One of its constituents, lianas, is spreading and increasing in abundance on a global scale. This is particularly concerning as lianas negatively impact forests' carbon fluxes, dynamics, and overall resilience, potentially exacerbating both crises. While possibly linked to climate-change-induced atmospheric CO2 elevation and drought intensification, the reasons behind their increasing abundance remain elusive. Prior research shows distinct physiological differences between lianas and trees, but it is unclear whether these differences confer a demographic advantage to lianas with climate change. Guided by extensive datasets collected in Panamanian tropical forests, we developed a tractable model integrating physiology, demography, and epidemiology. Our findings suggest that CO2 fertilization, a climate change factor promoting forest productivity, gives lianas a demographic advantage. Conversely, factors such as extreme drought generally cause a decrease in liana prevalence. Such a decline in liana prevalence is expected from a physiological point of view because lianas have drought-sensitive traits. However, our analysis underscores the importance of not exclusively relying on physiological processes, as interactions with demographic mechanisms (i.e., the forest structure) can contrast these expectations, causing an increase in lianas with drought. Similarly, our results emphasize that identical physiological responses between lianas and trees still lead to liana increase. Even if lianas exhibit collinear but weaker responses in their performance compared to trees, a temporary liana prevalence increase might manifest driven by the faster response time of lianas imposed by their distinct life-history strategies than trees.
Assuntos
Mudança Climática , Árvores , Árvores/fisiologia , Árvores/crescimento & desenvolvimento , Florestas , Secas , Clima Tropical , Biodiversidade , EcossistemaRESUMO
Only 30% of embryos from in vitro fertilized oocytes successfully implant and develop to term, leading to repeated transfer cycles. To reduce time-to-pregnancy and stress for patients, there is a need for a diagnostic tool to better select embryos and oocytes based on their physiology. The current standard employs brightfield imaging, which provides limited physiological information. Here, we introduce METAPHOR: Metabolic Evaluation through Phasor-based Hyperspectral Imaging and Organelle Recognition. This non-invasive, label-free imaging method combines two-photon illumination and AI to deliver the metabolic profile of embryos and oocytes based on intrinsic autofluorescence signals. We used it to classify i) mouse blastocysts cultured under standard conditions or with depletion of selected metabolites (glucose, pyruvate, lactate); and ii) oocytes from young and old mouse females, or in vitro-aged oocytes. The imaging process was safe for blastocysts and oocytes. The METAPHOR classification of control vs. metabolites-depleted embryos reached an area under the ROC curve (AUC) of 93.7%, compared to 51% achieved for human grading using brightfield imaging. The binary classification of young vs. old/in vitro-aged oocytes and their blastulation prediction using METAPHOR reached an AUC of 96.2% and 82.2%, respectively. Finally, organelle recognition and segmentation based on the flavin adenine dinucleotide signal revealed that quantification of mitochondria size and distribution can be used as a biomarker to classify oocytes and embryos. The performance and safety of the method highlight the accuracy of noninvasive metabolic imaging as a complementary approach to evaluate oocytes and embryos based on their physiology.
Assuntos
Blastocisto , Oócitos , Animais , Blastocisto/metabolismo , Camundongos , Oócitos/metabolismo , Feminino , Organelas/metabolismo , Imagem Óptica/métodosRESUMO
Cytosolic sensing of nucleic acids initiates tightly regulated programs to limit infection. Oocyte fertilization represents a scenario wherein inappropriate responses to exogenous yet non-pathogen-derived nucleic acids would have negative consequences. We hypothesized that germ cells express negative regulators of nucleic acid sensing (NAS) in steady state and applied an integrated data-mining and functional genomics approach to identify a rheostat of DNA and RNA sensing-the inflammasome component NLRP14. We demonstrated that NLRP14 interacted physically with the nucleic acid sensing pathway and targeted TBK1 (TANK binding kinase 1) for ubiquitination and degradation. We further mapped domains in NLRP14 and TBK1 that mediated the inhibitory function. Finally, we identified a human nonsense germline variant associated with male sterility that results in loss of NLRP14 function and hyper-responsiveness to nucleic acids. The discovery points to a mechanism of nucleic acid sensing regulation that may be of particular importance in fertilization.
Assuntos
Fertilização/imunologia , Células Germinativas/imunologia , Inflamassomos/imunologia , Ácidos Nucleicos/imunologia , Nucleosídeo-Trifosfatase/imunologia , Células A549 , Animais , Chlorocebus aethiops , Citosol/imunologia , Citosol/metabolismo , Feminino , Fertilização/genética , Expressão Gênica/imunologia , Células Germinativas/metabolismo , Mutação em Linhagem Germinativa/imunologia , Células HEK293 , Humanos , Immunoblotting , Infertilidade Masculina/genética , Infertilidade Masculina/imunologia , Inflamassomos/genética , Inflamassomos/metabolismo , Masculino , Ácidos Nucleicos/metabolismo , Nucleosídeo-Trifosfatase/genética , Nucleosídeo-Trifosfatase/metabolismo , Ligação Proteica/imunologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Células VeroRESUMO
Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. How their biosynthesis is regulated during spermiogenesis has largely remained elusive. Here, we show that 1700029I15Rik knockout male mice are severely subfertile and their spermatozoa do not fuse with eggs. 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. It interacts with proteins involved in N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. The ablation of 1700029I15Rik destabilizes non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for N-glycosylation. The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. Our results support for a specific, 1700029I15Rik-mediated pathway underpinning the biosynthesis of acrosomal membrane proteins during spermiogenesis.
Assuntos
Acrossomo , Proteínas de Membrana , Animais , Masculino , Camundongos , Acrossomo/metabolismo , Mamíferos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Knockout , Sêmen/metabolismo , Proteínas de Plasma Seminal/metabolismo , Interações Espermatozoide-Óvulo , Espermatozoides/metabolismo , Óvulo/metabolismoRESUMO
Increasing Asian dust fluxes, associated with late Cenozoic cooling and intensified glaciations, are conventionally thought to drive iron fertilization of phytoplankton productivity in the North Pacific, contributing to ocean carbon storage and drawdown of atmospheric CO2. During the early Pleistocene glaciations, however, productivity remained low despite higher Asian dust fluxes, only displaying glacial stage increases after the mid-Pleistocene climate transition (~800 ka B.P.). We solve this paradox by analyzing an Asian dust sequence, spanning the last 3.6 My, from the Tarim Basin, identifying a major switch in the iron composition of the dust at ~800 ka, associated with expansion of Tibetan glaciers and enhanced production of freshly ground rock minerals. This compositional shift in the Asian dust was recorded synchronously in the downwind, deep sea sediments of the central North Pacific. The switch from desert dust, containing stable, highly oxidized iron, to glacial dust, richer in reactive reduced iron, coincided with increased populations of silica-producing phytoplankton in the equatorial North Pacific and increased primary productivity in more northerly locations, such as the South China Sea. We calculate that potentially bioavailable Fe2+ flux to the North Pacific was more than doubled after the switch to glacially- sourced dust. These findings indicate a positive feedback between Tibetan glaciations, glaciogenic production of dust with enhanced iron bioavailability, and changes in North Pacific iron fertilization. Notably, this strengthened link between climate and eolian dust coincided with the mid-Pleistocene transition to increased storage of C in the glacial North Pacific and more intense northern hemisphere glaciations.
RESUMO
Physical exercise is a robust lifestyle intervention known for its enhancement of cognitive abilities. Nevertheless, the extent to which these benefits can be transmitted across generations (intergenerational inheritance to F1, and transgenerational to F2 and beyond) remains a topic of limited comprehension. We have already shown that cognitive improvements resulting from physical exercise can be inherited from parents to their offspring, proving intergenerational effects. So, we set out to explore whether these enhancements might extend transgenerationally, impacting the F2 generation. In this study, we initially examined the behavioral traits of second generation (F2) male mice, whose grandfathers (F0) had an exercise intervention. Our findings revealed that F2 mice with physically active grandpaternal F0 progenitors displayed significantly improved memory recall, encompassing both spatial and non-spatial information when compared to their counterparts from sedentary F0 progenitors, and proving for the first time the transgenerational inheritance of physical exercise induced cognitive enhancement. Surprisingly, while F2 memory improved (as was the case with F1), adult hippocampal neurogenesis remained unchanged between experimental and control groups (unlike in F1). Additionally, our analysis of small RNA sequences in the hippocampus identified 35 differentially expressed miRNAs linked to important brain function categories. Notably, two of these miRNAs, miRNA-144 and miRNA-298, displayed a robust negative correlation with cognitive performance. These findings highlight the enduring transgenerational transmission of cognitive benefits associated with exercise, even after two generations, suggesting that moderate exercise training can have lasting positive effects, possibly orchestrated by a specific set of miRNAs that exert their influence across multiple generations.
Assuntos
Cognição , Hipocampo , Condicionamento Físico Animal , Animais , Masculino , Camundongos , Cognição/fisiologia , Condicionamento Físico Animal/fisiologia , Hipocampo/fisiologia , Hipocampo/metabolismo , Feminino , Neurogênese/fisiologia , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/genéticaRESUMO
The Dobbs decision of the United States Supreme Court and the actions of several state legislatures have made it risky, if not outright dangerous, to teach factual material concerning human embryology. At some state universities, for instance, if a professor's lecture is felt to teach or discuss abortion (as it might when teaching about tubal pregnancies, hydatidiform moles, or eneuploidy), that instructor risks imprisonment for up to 14 years (Gyori, 2023). Some states' new censorship rules have thus caused professors to drop modules on abortion from numerous science and humanities courses. In most states, instructors can still teach about human embryonic development and not risk putting their careers or livelihoods in jeopardy. However, even in many of these institutions, students can bring a professor to a disciplinary hearing by claiming that the instructor failed to provide ample trigger warnings on such issues. This essay attempts to provide some strategies wherein human embryology and the ethical issues surrounding it might be taught and students may be given resources to counter unscientific falsehoods about fertilization and human development. This essay provides evidence for teaching the following propositions. Mis-information about human biology and medicine is rampant on the internet, and there are skills that can be taught to students that will help them determine which sites should trusted. This is a skill that needs to be taught as part of science courses.
Assuntos
Embriologia , Humanos , Estados Unidos , Embriologia/educação , Início da Vida Humana , Aborto Induzido/educação , Feminino , Gravidez , EnsinoRESUMO
Testis angiotensin-converting enzyme (tACE) plays a critical role in male fertility, but the mechanism is unknown. By using ACE C-domain KO (CKO) mice which lack tACE activity, we found that ATP in CKO sperm was 9.4-fold lower than WT sperm. Similarly, an ACE inhibitor (ACEi) reduced ATP production in mouse sperm by 72%. Metabolic profiling showed that tACE inactivation severely affects oxidative metabolism with decreases in several Krebs cycle intermediates including citric acid, cis-aconitic acid, NAD, α-ketoglutaric acid, succinate, and L-malic acid. We found that sperms lacking tACE activity displayed lower levels of oxidative enzymes (CISY, ODO1, MDHM, QCR2, SDHA, FUMH, CPT2, and ATPA) leading to a decreased mitochondrial respiration rate. The reduced energy production in CKO sperms leads to defects in their physiological functions including motility, acrosine activity, and fertilization in vitro and in vivo. Male mice treated with ACEi show severe impairment in reproductive capacity when mated with female mice. In contrast, an angiotensin II receptor blocker (ARB) had no effect. CKO sperms express significantly less peroxisome proliferators-activated receptor gamma (PPARγ) transcription factor, and its blockade eliminates the functional differences between CKO and WT sperms, indicating PPARγ might mediate the effects of tACE on sperm metabolism. Finally, in a cohort of human volunteers, in vitro treatment with the ramipril or a PPARγ inhibitor reduced ATP production in human sperm and hence its motility and acrosine activity. These findings may have clinical significance since millions of people take ACEi daily, including men who are reproductively active.
Assuntos
Fertilização , PPAR gama , Peptidil Dipeptidase A , Espermatozoides , Animais , Feminino , Humanos , Masculino , Camundongos , Trifosfato de Adenosina/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Fertilização/genética , PPAR gama/genética , PPAR gama/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/enzimologia , Camundongos Endogâmicos C57BL , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Proteínas Mitocondriais/genética , Técnicas de Inativação de Genes , Fosforilação OxidativaRESUMO
Potatoes (Solanum tuberosum L.) are a fundamental staple for millions of people worldwide. They provide essential amino acids, vitamins, and starch - a vital component of the human diet, providing energy and serving as a source of fiber. Unfortunately, global warming is posing a severe threat to this crop, leading to significant yield losses, and thereby endangering global food security. Industrial agriculture traditionally relies on excessive nitrogen (N) fertilization to boost yields. However, it remains uncertain whether this is effective in combating heat-related yield losses of potato. Therefore, our study aimed to investigate the combinatory effects of heat stress and N fertilization on potato tuber formation. We demonstrate that N levels and heat significantly impact tuber development. The combination of high N and heat delays tuberization, while N deficiency initiates early tuberization, likely through starvation-induced signals, independent of SELF-PRUNING 6A (SP6A), a critical regulator of tuberization. We also found that high N levels in combination with heat reduce tuber yield rather than improve it. However, our study revealed that SP6A overexpression can promote tuberization under these inhibiting conditions. By utilizing the excess of N for accumulating tuber biomass, SP6A overexpressing plants exhibit a shift in biomass distribution towards the tubers. This results in an increased yield compared to wild-type plants. Our results highlight the role of SP6A overexpression as a viable strategy for ensuring stable potato yields in the face of global warming. As such, our findings provide insights into the complex factors impacting potato crop productivity.
Assuntos
Solanum tuberosum , Humanos , Temperatura , Nitrogênio/metabolismo , Fertilização , Tubérculos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Distyly is an iconic floral polymorphism governed by a supergene, which promotes efficient pollen transfer and outcrossing through reciprocal differences in the position of sexual organs in flowers, often coupled with heteromorphic self-incompatibility. Distyly has evolved convergently in multiple flowering plant lineages, but has also broken down repeatedly, often resulting in homostylous, self-compatible populations with elevated rates of self-fertilization. Here, we aimed to study the genetic causes and genomic consequences of the shift to homostyly in Linum trigynum, which is closely related to distylous Linum tenue. Building on a high-quality genome assembly, we show that L. trigynum harbors a genomic region homologous to the dominant haplotype of the distyly supergene conferring long stamens and short styles in L. tenue, suggesting that loss of distyly first occurred in a short-styled individual. In contrast to homostylous Primula and Fagopyrum, L. trigynum harbors no fixed loss-of-function mutations in coding sequences of S-linked distyly candidate genes. Instead, floral gene expression analyses and controlled crosses suggest that mutations downregulating the S-linked LtWDR-44 candidate gene for male self-incompatibility and/or anther height could underlie homostyly and self-compatibility in L. trigynum. Population genomic analyses of 224 whole-genome sequences further demonstrate that L. trigynum is highly self-fertilizing, exhibits significantly lower genetic diversity genome-wide, and is experiencing relaxed purifying selection and less frequent positive selection on nonsynonymous mutations relative to L. tenue. Our analyses shed light on the loss of distyly in L. trigynum, and advance our understanding of a common evolutionary transition in flowering plants.
Assuntos
Flores , Genoma de Planta , Flores/genéticaRESUMO
The CatSper cation channel is essential for sperm capacitation and male fertility. The multi-subunit CatSper complexes form highly organized calcium signaling nanodomains on flagellar membranes. Here, we report identification of an uncharacterized protein, C2CD6, as a subunit of the mouse CatSper complex. C2CD6 contains a calcium-dependent, membrane-targeting C2 domain. C2CD6 associates with the CatSper calcium-selective, core-forming subunits. Deficiency of C2CD6 depletes the CatSper nanodomains from the flagellum and results in male sterility. C2CD6-deficient sperm are defective in hyperactivation and fail to fertilize oocytes both in vitro and in vivo. CatSper currents are present but at a significantly lower level in C2CD6-deficient sperm. Transient treatments with either Ca2+ ionophore, starvation, or a combination of both restore the fertilization capacity of C2CD6-deficient sperm. C2CD6 interacts with EFCAB9, a pH-dependent calcium sensor in the CatSper complex. We postulate that C2CD6 facilitates incorporation of the CatSper complex into the flagellar plasma membrane and may function as a calcium sensor. The identification of C2CD6 may enable the long-sought reconstitution of the CatSper ion channel complex in a heterologous system for male contraceptive development.
Assuntos
Canais de Cálcio , Infertilidade Masculina , Cauda do Espermatozoide , Animais , Feminino , Masculino , Camundongos , Potenciais de Ação , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Infertilidade Masculina/genética , Camundongos Endogâmicos C57BL , Multimerização Proteica , Transporte Proteico , Motilidade dos Espermatozoides , Cauda do Espermatozoide/metabolismo , Cauda do Espermatozoide/fisiologiaRESUMO
In most sexually reproducing animals, sperm entry provides the signal to initiate the final stages of female meiosis. In Caenorhabditis elegans, this signal is required for completion of female anaphase I and entry into meiosis II (MII). memi-1/2/3 (meiosis-to-mitosis) encode maternal components that facilitate this process; memi-1/2/3(RNAi) results in a skipped-MII phenotype. Previously, we used a gain-of-function mutation, memi-1(sb41), to identify genetic suppressors that represent candidates for the sperm-delivered signal. Herein, we characterize two suppressors of memi-1(sb41): gskl-1 and gskl-2. Both genes encode functionally redundant sperm glycogen synthase kinase, type 3 (GSK3) protein kinases. Loss of both genes causes defects in male spermatogenesis, sperm pseudopod treadmilling and paternal-effect embryonic lethality. The two kinases locate within the pseudopod of activated sperm, suggesting that they directly or indirectly regulate the sperm cytoskeletal polymer major sperm protein (MSP). The GSK3 genes genetically interact with another memi-1(sb41) suppressor, gsp-4, which encodes a sperm-specific PP1 phosphatase, previously proposed to regulate MSP dynamics. Moreover, gskl-2 gsp-4; gskl-1 triple mutants often skip female MII, similar to memi-1/2/3(RNAi). The GSK3 kinases and PP1 phosphatases perform similar sperm-related functions and work together for post-fertilization functions in the oocyte that involve MEMI.