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An unintended consequence of global change is an increase in opportunities for hybridization among previously isolated lineages. Here we illustrate how global change can facilitate the breakdown of reproductive barriers and the formation of hybrids, drawing on the flora of the British Isles for insight. Although global change may ameliorate some of the barriers preventing hybrid establishment, for example by providing new ecological niches for hybrids, it will have limited effects on environment-independent post-zygotic barriers. For example, genic incompatibilities and differences in chromosome numbers and structure within hybrid genomes are unlikely to be affected by global change.Wethus speculate that global change will have a larger effect on eroding pre-zygotic barriers (eco-geographical isolation and phenology) than post-zygotic barriers, shifting the relative importance of these two classes of reproductive barriers from what is usually seen in naturally produced hybrids where pre-zygotic barriers are the largest contributors to reproductive isolation. Although the long-term fate of neo-hybrids is still to be determined, the massive impact of global change on the dynamics and distribution of biodiversity generates an unprecedented opportunity to study large numbers of unpredicted, and often replicated, hybridization ‘experiments’, allowing us to peer into the birth and death of evolutionary lineages.

Background and Objectives: Fertilized zygotes normally display two pronuclei (PN), but abnormal fertilization patterns (0, 1 or >2PN) are observed daily in IVF labs. Multiple PN zygotes (>2) are generally discarded due to an increased risk of aneuploidy. However, the decision to transfer or not transfer 1PN-derived embryos remains controversial. The aims of our study were to analyze the neonatal outcomes of fresh or frozen–thawed embryos derived from 1PN zygotes, and to evaluate the influence of the fertilization method. Materials and Methods: Data were retrospectively collected from cycles performed between January 2018 and December 2022. Fresh cycles were analyzed for the comparative fate of 1PN zygotes (n = 1234) following conventional in vitro fertilization (cIVF; n = 648) or intracytoplasmic sperm injection (ICSI; n = 586), as well as the results of the 64 transfers of 1PN-derived embryos (pregnancy rate (PR) and neonatal outcomes). This pregnancy follow-up was also applied to 167 transfers of frozen–thawed 1PN-derived embryos. Results: In fresh cycles, 46% of the 1PN zygotes in the cIVF group developed into embryos of sufficient quality to be transferred or frozen (day 3 or 5/6). This rate was lower in the fresh ICSI cycles (33%). Blastulation rate was also significantly higher in the cIVF group (44%) in comparison to the ICSI group (20%). The fresh single embryo transfers (32 per group) allowed seven pregnancies in the cIVF group (PR = 21.9%) as compared to four pregnancies in the ICSI group (PR = 12.5%). In the cIVF group, five deliveries of healthy newborns were achieved, but only one in the ICSI group. In frozen/thawed cycles, 36 pregnancies were obtained out of the 167 transfers. A non-significant difference was observed between embryos derived from cIVF cycles (PR = 26%) and ICSI cycles (PR = 16%) with 18 and 8 healthy babies born, respectively. Conclusions: We observed better outcomes for 1PN zygotes in cIVF cycles in comparison to ICSI cycles. Our center policy to transfer good-quality 1PN-derived embryos allowed the birth of 32 healthy babies.

Survey of postzygotic mosaic mutations (PZMs) in 5,947 trios with autism spectrum disorders (ASD) discovers differences in mutational properties between germline mutations and PZMs. Spatiotemporal analyses of the PZMs also revealed the association of the amygdala with ASD and implicated risk genes, including recurrent potential gain-of-function mutations in SMARCA4 . We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls ( P < 1 × 10 −6 ), and genes carrying these PZMs were enriched for expression in the amygdala ( P = 5.4 × 10 −3 ). Two genes ( KLF16 and MSANTD2 ) were significantly enriched for PZMs genome-wide, and other PZMs involved genes ( SCN2A , HNRNPU and SMARCA4 ) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.

Zygotes are used to create genetically modified animals by electroporation using the CRISPR-Cas9 system. Such zygotes in rats are obtained from superovulated female rats after mating. Recently, we reported that in vivo- fertilized zygotes had higher cryotolerance and developmental ability than in vitro- fertilized zygotes in Sprague Dawley (SD) and Fischer 344 rats. To apply the in vitro -fertilized zygotes in creating genetically modified rats, we need to address their low cryotolerance and developmental ability. Hence, we evaluated the effects of warming solutions containing different sucrose concentrations (0–0.3 M) and the oocyte donor’s age (3–7-week-old SD rats) on the viability of vitrified-warmed zygotes after in vitro fertilization and on developmental ability by embryo transfer in SD rats. A warming solution containing 0.1 M sucrose enhanced the survival rate of vitrified-warmed zygotes and their rate of development to two-cell embryos. Additionally, zygotes derived from 6- and 7-week-old female rats had higher cryotolerance and developmental ability than those from 3-week-old ones. Next, vitrified-warmed rat zygotes produced using the optimized protocol underwent genome editing by electroporation with Cas9 ribonucleoprotein and gRNA introduced to disrupt the Tyr gene. We then found that 86.5% of the pups derived from zygotes demonstrated mutation of the targeted gene. Therefore, the improved protocol for vitrifying and warming rat zygotes is useful for preserving and producing genetically modified rats.

Summary Modest dietary restriction extends lifespan (LS) in a diverse range of taxa and typically has a larger effect in females than males. Traditionally, this has been attributed to a stronger trade-off between LS and reproduction in females than in males that is mediated by the intake of calories. Recent studies, however, suggest that it is the intake of specific nutrients that extends LS and mediates this trade-off. Here, we used the geometric framework (GF) to examine the sex-specific effects of protein (P) and carbohydrate (C) intake on LS and reproduction in Drosophila melanogaster. We found that LS was maximized at a high intake of C and a low intake of P in both sexes, whereas nutrient intake had divergent effects on reproduction. Male offspring production rate and LS were maximized at the same intake of nutrients, whereas female egg production rate was maximized at a high intake of diets with a P:C ratio of 1:2. This resulted in larger differences in nutrient-dependent optima for LS and reproduction in females than in males, as well as an optimal intake of nutrients for lifetime reproduction that differed between the sexes. Under dietary choice, the sexes followed similar feeding trajectories regulated around a P:C ratio of 1:4. Consequently, neither sex reached their nutritional optimum for lifetime reproduction, suggesting intralocus sexual conflict over nutrient optimization. Our study shows clear sex differences in the nutritional requirements of reproduction in D. melanogaster and joins the growing list of studies challenging the role of caloric restriction in extending LS.

Elevated concentrations of serum non-esterified fatty acids (NEFA), associated with maternal disorders such as obesity and type II diabetes, alter the ovarian follicular micro-environment and have been associated with subfertility arising from reduced oocyte developmental competence. We have asked whether elevated NEFA concentrations during oocyte maturation affect the development and physiology of zygotes formed from such oocytes, using the cow as a model. The zygotes were grown to blastocysts, which were evaluated for their quality in terms of cell number, apoptosis, expression of key genes, amino acid turnover and oxidative metabolism. Oocyte maturation under elevated NEFA concentrations resulted in blastocysts with significantly lower cell number, increased apoptotic cell ratio and altered mRNA abundance of DNMT3A, IGF2R and SLC2A1. In addition, the blastocysts displayed reduced oxygen, pyruvate and glucose consumption, up-regulated lactate consumption and higher amino acid metabolism. These data indicate that exposure of maturing oocytes to elevated NEFA concentrations has a negative impact on fertility not only through a reduction in oocyte developmental capacity but through compromised early embryo quality, viability and metabolism.

In flowering plants, the asymmetrical division of the zygote is the first hallmark of apical-basal polarity of the embryo and is controlled by a MAP kinase pathway that includes the MAPKKK YODA (YDA). In Arabidopsis, YDA is activated by the membrane-associated pseudokinase SHORT SUSPENSOR (SSP) through an unusual parent-of-origin effect: SSP transcripts accumulate specifically in sperm cells but are translationally silent. Only after fertilization is SSP protein transiently produced in the zygote, presumably from paternally inherited transcripts. SSP is a recently diverged, Brassicaceae-specific member of the BRASSINOSTEROID SIGNALING KINASE (BSK) family. BSK proteins typically play broadly overlapping roles as receptor-associated signaling partners in various receptor kinase pathways involved in growth and innate immunity. This raises two questions: How did a protein with generic function involved in signal relay acquire the property of a signal-like patterning cue, and how is the early patterning process activated in plants outside the Brassicaceae family, where SSP orthologs are absent? Here, we show that Arabidopsis BSK1 and BSK2, two close paralogs of SSP that are conserved in flowering plants, are involved in several YDA-dependent signaling events, including embryogenesis. However, the contribution of SSP to YDA activation in the early embryo does not overlap with the contributions of BSK1 and BSK2. The loss of an intramolecular regulatory interaction enables SSP to constitutively activate the YDA signaling pathway, and thus initiates apical-basal patterning as soon as SSP protein is translated after fertilization and without the necessity of invoking canonical receptor activation.

This multicenter cohort study on embryo assessment and outcome data from 11,744 IVF/ICSI cycles with 104,830 oocytes and 42,074 embryos, presents the effect of women's age on oocyte, zygote, embryo morphology and cleavage parameters, as well as cycle outcome measures corrected for confounding factors as center, partner's age and referral diagnosis. Cycle outcome data confirmed the well-known effect of women's age. Oocyte nuclear maturation and proportion of 2 pro-nuclear (2PN) zygotes were not affected by age, while a significant increase in 3PN zygotes was observed in both IVF and ICSI (p<0.0001) with increasing age. Maternal age had no effect on cleavage parameters or on the morphology of the embryo day 2 post insemination. Interestingly, initial hCG value after single embryo transfer followed by ongoing pregnancy was increased with age in both IVF (p = 0.007) and ICSI (p = 0.001) cycles. For the first time, we show that a woman's age does impose a significant footprint on early embryo morphological development (3PN). In addition, the developmentally competent embryos were associated with increased initial hCG values as the age of the women increased. Further studies are needed to elucidate, if this increase in initial hCG value with advancing maternal age is connected to the embryo or the uterus.

A comparison of eudicot and monocot model plants explores recent advances and open questions on gene regulatory networks during zygote development, parental influences on early embryogenesis, zygotic genome activation, and cell fate determination.

The causes of embryonic arrest during pre-implantation development are poorly understood. Attempts to correlate patterns of oocyte gene expression with successful embryo development have been hampered by the lack of reliable and nondestructive predictors of viability at such an early stage. Here we report that zygote viscoelastic properties can predict blastocyst formation in humans and mice within hours after fertilization, with >90% precision, 95% specificity and 75% sensitivity. We demonstrate that there are significant differences between the transcriptomes of viable and non-viable zygotes, especially in expression of genes important for oocyte maturation. In addition, we show that low-quality oocytes may undergo insufficient cortical granule release and zona-hardening, causing altered mechanics after fertilization. Our results suggest that embryo potential is largely determined by the quality and maturation of the oocyte before fertilization, and can be predicted through a minimally invasive mechanical measurement at the zygote stage. Reliable assessments of oocyte developmental potential are lacking, making it difficult to select the best quality embryos for transfer after in vitro fertilization. Here, the authors show that a non-invasive measurement of viscoelastic properties predicts developmental potential in both humans and mice.