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Recent breakthroughs in stem cell differentiation and reprogramming suggest that functional human gametes could soon be created in vitro. While the ethical debate on the uses of in vitro generated gametes (IVG) was originally constrained by the fact that they could be derived only from embryonic stem cell lines, the advent of somatic cell reprogramming, with the possibility to easily derive human induced pluripotent stem cells from any individual, affords now a major leap in the feasibility of IVG derivation and in the scope of their potential applications. In this paper we develop an ethical framework, rooted in recent scientific evidence, to support a robust experimental pipeline that could enable the first-in-human use of IVG. We then apply this framework to the following objectives: (1) a clarification of the genetic parenting options afforded by IVG, along with their ethical underpinnings; (2) a defence of the use of IVG to remedy infertility, broadening their scope to same-sex couples; (3) an assessment of the most far-reaching implications of IVG for multiplex parenting. These include, first, the liberation of parenting roles from the constraints of biological generations in vivo, allowing multiple individuals to engage in genetic parenting together, thus blurring the distinction between biological and social generations. Second, we discuss the conflation of IVG with sequencing technology and its implications for the possibility that prospective parents may choose among a hitherto unprecedented number of potential children. In view of these perspectives, we argue that, contrary to the exhausted paradigm according to which society lags behind science, IVG may represent instead a salient and most visible instance where biotechnological ingenuity could be used in pursuit of social experimentation.

Background The artificial induction of unreduced (2n) gametes, due to first division restitution (FDR) or second division restitution (SDR), is an important method to produce triploids in higher plants. It is crucial to evaluate the genetic composition and heterozygosity transmission of induced 2n gametes with different formation mechanisms. Results Here, we produced 110 triploids by pollinating the female inflorescence of Populus alba × P. glandulosa with gibberellin-induced 2n pollen of Populus bolleana . The genetic composition and heterozygosity of the induced 2n pollen were inferred from SSR marker analysis of the triploid offspring, using 27 primer pairs distributed across nine Populus chromosomes. This revealed that, among the 110 hybrid triploids, 70 triploids did originate from FDR-type 2n pollen and the other 40 from SDR-type 2n pollen. The FDR-type and SDR-type 2n pollen transmitted a substantially different level of parental heterozygosity (0.7545 and 0.3167, respectively) in P. bolleana . Additionally, compared with the low coefficient of variation (CV = 12.82%) for heterozygosity transmitted by FDR-type 2n pollen, there was much higher coefficient of variation (CV = 48.82%) for that transmitted by SDR-type 2n pollen. Conclusions Our findings provide a valuable reference point for bolstering suitable applications of 2n gametes in future research, and can help foster new strategies of triploid breeding in plants. Clinical trial nubmer Not applicable.

Fertilization involving unreduced (2n) gametes is considered the dominant mechanism of polyploid formation in angiosperms; however, our knowledge of the prevalence of and evolutionary mechanisms maintaining 2n gametes in natural populations is limited. We hypothesize that 2n gametes are deleterious consequences of meiotic errors maintained by mutation–selection balance and should increase in species with relaxed opportunities for selection on sexual processes (asexuality), reduced efficacy of selection (asexuality, selfing) and increased genome instability (high chromosome number). We used flow cytometry to estimate male 2n gamete production in 60 populations from 24 species of Brassicaceae. We quantified variation in 2n gamete production within and among species, and examined associations with life history, reproductive mode, genome size and chromosomal number while accounting for phylogeny. Most individuals produced < 2% 2n male gametes, whereas a small number had > 5% (up to 85%) production. Variation in 2n gamete production was significant among species and related to reproductive system; asexual species produced significantly more 2n gametes than mixed-mating and outcrossing species. Our results, unique in their multi-species perspective, are consistent with 2n gametes being deleterious but maintained when opportunities for selection are limited. Rare individuals with elevated 2n gamete production may be key contributors to polyploid formation.

Companies and academic laboratories are pursuing the production of gametes from stem cells. Researchers should be active participants in discussions about speculative scenarios, to avoid this endeavor to accommodate genetic parenthood undermines the value it is meant to serve, because of either unrealistic or insufficient ethical reflection.

Sexual reproduction involves the fusion of two gametes of opposite sex. Although the sperm-expressed fusogen HAPLESS 2 (HAP2) or GENERATIVE CELL SPECIFIC 1 (GCS1) plays a vital role in this process in many eukaryotic organisms and an understanding of its regulation is emerging in unicellular systems [J. Zhang et al., Nat. Commun. 12, 4380 (2021); J. F. Pinello et al. Dev. Cell 56, 3380–3392.e9 (2021)], neither HAP2/GCS1 interactors nor mechanisms for delivery and activation at the fusion site are known in multicellular plants. Here, we show that Arabidopsis thaliana HAP2/GCS1 interacts with two sperm DUF679 membrane proteins (DMP8 and DMP9), which are required for the EGG CELL 1 (EC1)-induced translocation of HAP2/GCS1 from internal storage vesicle to the sperm plasma membrane to ensure successful fertilization. Our studies in Arabidopsis and tobacco provide evidence for a conserved function of DMP8/9-like proteins as HAP2/GCS1 partner in seed plants. Our data suggest that seed plants evolved a DMP8/9-dependent fusogen translocation process to achieve timely acquisition of sperm fusion competence in response to egg cell–derived signals, revealing a previously unknown critical step for successful fertilization.

Polyploids, organisms with more than two sets of chromosomes, are widespread in flowering plants, including many important crop species. Increases in ploidy level are believed to arise commonly through the production of gametes that have not had their ploidy level reduced during meiosis. Although there have been cytological descriptions of unreduced gamete formation in a number of plants, until recently none of the underlying genes or molecular mechanisms involved in unreduced gamete production have been described. The recent discovery of several genes in which mutations give rise to a high frequency of unreduced gametes in the model plant Arabidopsis thaliana opens the door to the elucidation of this important event and its manipulation in crop species. Here this recent progress is reviewed and the identified genes and the mechanism by which the loss of protein function leads to the formation of unreduced gametes are discussed. The potential to use the knowledge gained from Arabidopsis mutants to design tools and develop techniques to engineer unreduced gamete production in important crop species for use in plant breeding is also discussed.

Polyploidization is associated with lineage-specific changes that promote divergence and speciation. Knowledge about the establishment of neopolyploids is fragmentary. We use an open-source multi-agent software to build a scalable easy-to-use command center for analysing complex diploid-polyploid interactions. The workspace is a multilayered environment whose eco-variables fluctuate between generations. Reproductive syndromes, recombinant/clonal inheritance and complex traits (adaptivity, niche breadth, dispersal) are used to elicit fitness values and monitor population spatial dynamics. Neopolyploidization was recurrent, polytopic and heterogeneous in time. Increasing rates of unreduced gametes accelerated the establishment of neopolyploids but removed the role of triploids. Under standard rates and heterogeneous environment, model-based evidence shows that (1) a large proportion of polyploidization events are unsuccessful, (2) parental traits and local conditions prime a loss of diploid fitness that benefited eco-geographic structured polyploid success, (3) self-fertility and apomixis improve the rate of polyploidization, and shorten the time required for demographic establishment, and (4) ecological niche shifts promote cytotype coexistence, but niche expansion favors establishment and foster cytotype displacement. The modelling framework offers opportunities for in-depth lineage-specific analyses of the spatiotemporal dynamics and evolutionary differentiation in diploid-polyploid systems.

Polyploidization is a widespread phenomenon, especially in flowering plants that have all undergone at least one event of whole genome duplication during their evolutionary history. Consequently, a large range of plants, including many of the world's crops, combines more than two sets of chromosomes originating from the same (autopolyploids) or related species (allopolyploids). Depending on the polyploid formation pathway, different patterns of recombination will be promoted, conditioning the level of heterozygosity. A polyploid population harboring a high level of heterozygosity will produce more genetically diverse progenies. Some of these individuals may show a better adaptability to different ecological niches, increasing their chance for successful establishment through natural selection. Another condition for young polyploids to survive corresponds to the formation of well-balanced gametes, assuring a sufficient level of fertility. In this review, we discuss the consequences of polyploid formation pathways, meiotic behavior and recombination regulation on the speciation success and maintenance of polyploid species.

In the plant kingdom, events of whole genome duplication or polyploidization are generally believed to occur via alterations of the sexual reproduction process. Thereby, diploid pollen and eggs are formed that contain the somatic number of chromosomes rather than the gametophytic number. By participating in fertilization, these so-called 2n gametes generate polyploid offspring and therefore constitute the basis for the establishment of polyploidy in plants. In addition, diplogamete formation, through meiotic restitution, is an essential component of apomixis and also serves as an important mechanism for the restoration of F1 hybrid fertility. Characterization of the cytological mechanisms and molecular factors underlying 2n gamete formation is therefore not only relevant for basic plant biology and evolution, but may also provide valuable cues for agricultural and biotechnological applications (e.g. reverse breeding, clonal seeds). Recent data have provided novel insights into the process of 2n pollen and egg formation and have revealed multiple means to the same end. Here, we summarize the cytological mechanisms and molecular regulatory networks underlying 2n gamete formation, and outline important mitotic and meiotic processes involved in the ectopic induction of sexual polyploidization.

Parental environmental factors, including diet, body composition, metabolism, and stress, affect the health and chronic disease risk of people throughout their lives, as captured in the Developmental Origins of Health and Disease concept. Research across the epidemiological, clinical, and basic science fields has identified the period around conception as being crucial for the processes mediating parental influences on the health of the next generation. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune, and neurological morbidities, often termed developmental programming. We review periconceptional induction of disease risk from four broad exposures: maternal overnutrition and obesity; maternal undernutrition; related paternal factors; and the use of assisted reproductive treatment. Studies in both humans and animal models have demonstrated the underlying biological mechanisms, including epigenetic, cellular, physiological, and metabolic processes. We also present a meta-analysis of mouse paternal and maternal protein undernutrition that suggests distinct parental periconceptional contributions to postnatal outcomes. We propose that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.