Long-Term Phenotypic and Proteomic Changes Following Vitrified Embryo Transfer in the Rabbit Model

[EN] This study was conducted to demonstrate how a vitrified embryo transfer procedure incurs phenotypic and molecular changes throughout life. This study reports the first evidence describing that embryonic manipulation during a vitrified embryo transfer cycle induced molecular modifications, concerning oxidative phosphorylation and dysregulations in zinc and lipid metabolism in liver tissue, which has been reported as responsible for postnatal variations of the phenotype. Nowadays, assisted reproductive technologies (ARTs) are considered valuable contributors to our past, but a future without their use is inconceivable. However, in recent years, several studies have evidenced a potential impact of ART on long-term development in mammal species. To date, the long-term follow-up data are still limited. So far, studies have mainly focused on in vitro fertilization or in vitro culture, with information from gametes/embryos cryopreservation field being practically missing. Herein, we report an approach to determine whether a vitrified embryo transfer procedure would have long-term consequences on the offspring. Using the rabbit as a model, we compared animals derived from vitrified-transferred embryos versus those naturally conceived, studying the growth performance, plus the weight throughout life, and the internal organs/tissues phenotype. The healthy status was assessed over the hematological and biochemical parameters in peripheral blood. Additionally, a comparative proteomic analysis was conducted in the liver tissue to investigate molecular cues related to vitrified embryo transfer in an adult tissue. After vitrified embryo transfer, birth weight was increased, and the growth performance was diminished in a sex-specific manner. In addition, vitrified-transferred animals showed significantly lower body, liver and heart weights in adulthood. Molecular analyses revealed that vitrified embryo transfer triggers reprogramming of the liver proteome. Functional analysis of the differentially expressed proteins showed changes in relation to oxidative phosphorylation and dysregulations in the zinc and lipid metabolism, which has been reported as possible causes of a disturbed growth pattern. Therefore, we conclude that vitrified embryo transfer is not a neutral procedure, and it incurs long-term effects in the offspring both at phenotypic and molecular levels. These results described a striking example of the developmental plasticity exhibited by the mammalian embryo.Funding from the Ministry of Economy, Industry and Competitiveness (Research project: AGL2017-85162-C2-1-R and AGL2014-53405-C2-1-P) is acknowledged. X.G.D. was supported by a research grant from the Ministry of Economy, Industry and Competitiveness (BES-2015-072429).Garcia-Dominguez, X.; Marco-Jiménez, F.; Peñaranda, D.; Vicente Antón, JS. (2020). Long-Term Phenotypic and Proteomic Changes Following Vitrified Embryo Transfer in the Rabbit Model. 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Feed restriction regime in a rabbit line selected for growth rate alters oocyte maturation manifested by alteration in msy2 gene expression

[EN] Young rabbit females selected for growth rate may have nutritional needs, which may not be met with the common practice of feed restriction during rearing in commercial rabbit production. The aim of this study was to analyse whether two different feeding programmes: ad libitum or restricted (130 g/day) feeding, applied in young rabbit females for 1 month at the end of rearing, could modulate the origin of ovulation process and the quality of the oocytes. At 16 weeks of age, 34 females were randomly assigned to restricted or ad libitum feeding, maintaining these conditions for a month. Then, in an initial experiment, transcriptional profiling of hypothalamus-hypophysis tissue was performed to assess failure to ovulate. In the second experiment, the gene expression analysis of some candidate genes related to oocytes quality was performed. Our results demonstrated that neither of the two feeding programmes modified the transcription of hypothalamus-hypophysis tissue, while the only differences in MSYR expression were found in in vivo mature oocytes ready for successful fertilization. Specifically, MSYR was over-expressed in oocytes from females fed ad libitum. MSYR is one of the most abundant proteins in the oocyte and has proven to be a key regulator of maternal RNA transcription and translation. This finding suggests that MSYR gene is a promising gene in our understanding of the relationship between high growth rate and reproductive performance decline.This work was supported by the Spanish Research Projects AGL2014-53405-C2-P and AGL2011-30170-C02-01 (CICYT). Carmen Naturil was supported by a research grant from the Education Ministry of the Valencian Regional Government (programme VALi+d. ACIF/2013/296).Naturil Alfonso, C.; Peñaranda, D.; Vicente Antón, JS.; Marco-Jiménez, F. (2017). 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Abelian duality on globally hyperbolic spacetimes

We study generalized electric/magnetic duality in Abelian gauge theory by combining techniques from locally covariant quantum field theory and Cheeger-Simons differential cohomology on the category of globally hyperbolic Lorentzian manifolds. Our approach generalizes previous treatments using the Hamiltonian formalism in a manifestly covariant way and without the assumption of compact Cauchy surfaces. We construct semi-classical configuration spaces and corresponding presymplectic Abelian groups of observables, which are quantized by the CCR-functor to the category of C*-algebras. We demonstrate explicitly how duality is implemented as a natural isomorphism between quantum field theories. We apply this formalism to develop a fully covariant quantum theory of self-dual fields

Lack of Methyl-CpG Binding Protein 2 (MeCP2) Affects Cell Fate Refinement During Embryonic Cortical Development

During differentiation, neurons progressively restrict their fate repressing the expression of specific genes. Here we describe the involvement in such developmental steps of the methyl-CpG binding protein 2 (MeCP2), an epigenetic factor that participates to chromatin folding and transcriptional regulation. We previously reported that, due to transcriptional impairments, the maturation of Mecp2 null neurons is delayed. To evaluate whether this could stem from altered progenitors proliferation and differentiation, we investigated whether lack of Mecp2 affects these features both in vitro and in vivo. We show that in Mecp2 null embryonic cortexes the expression of genes defining the identity of proliferating neuroprogenitors is enriched and that their permanence in the G1 phase is prolonged. Moreover, the number of cells transitioning from a stage of maturation to a more mature one is increased in Mecp2 null embryonic cortices, in line with the central role of G1 for cell identity refinement. We thus suggest that, possibly due to the lack of proper transcriptional control normally exerted by Mecp2, fate refinement is impaired in developing null cells. We propose that the maturation delay affecting the developing Mecp2 null cortex originates, at least in part, from deranged mechanisms of cell fate refinement

Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer

[EN] The advent of assisted reproductive technologies (ART) in mammals involved an extraordinary change in the environment where the beginning of a new organism takes place. Under in vitro conditions, in which ART is currently being performed, it likely fails to mimic optimal in vivo conditions. This suboptimal environment could mediate in the natural developmental trajectory of the embryo, inducing lasting effects until later life stages that may be inherited by subsequent generations (transgenerational effects). Therefore, we evaluated the potential transgenerational effects of embryo exposure to the cryopreservation-transfer procedure in a rabbit model on the offspring phenotype, molecular physiology of the liver (transcriptome and metabolome) and reproductive performance during three generations (F1, F2 and F3). The results showed that, compared to naturally-conceived animals (NC group), progeny generated after embryo exposure to the cryopreservation-transfer procedure (VT group) exhibited lower body growth, which incurred lower adult body weight in the F1 (direct effects), F2 (intergenerational effects) and F3 (transgenerational effects) generations. Furthermore, VT animals showed intergenerational effects on heart weight and transgenerational effects on liver weight. The RNA-seq data of liver tissue revealed 642 differentially expressed transcripts (DETs) in VT animals from the F1 generation. Of those, 133 were inherited from the F2 and 120 from the F3 generation. Accordingly, 151, 190 and 159 differentially accumulated metabolites (DAMs) were detected from the F1, F2 and F3, respectively. Moreover, targeted metabolomics analysis demonstrated that transgenerational effects were mostly presented in the non-polar fraction. Functional analysis of molecular data suggests weakened zinc and fatty acid metabolism across the generations, associated with alterations in a complex molecular network affecting global hepatic metabolism that could be associated with the phenotype of VT animals. However, these VT animals showed proper reproductive performance, which verified a functional health status. In conclusion, our results establish the long-term transgenerational effects following a vitrified embryo transfer procedure. We showed that the VT phenotype could be the result of the manifestation of embryonic developmental plasticity in response to the stressful conditions during ART procedures.Funding from the Ministry of Economy, Industry and Competitiveness (Research project: AGL2014-53405-C2-1-P) and Generalitat Valenciana (Research project: Prometeo II 2014/036) is acknowledged. X.G.D. was supported by a research grant from the Ministry of Economy, Industry and Competitiveness (BES-2015-072429). 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Early Embryo Exposure to Assisted Reproductive Manipulation Induced Subtle Changes in Liver Epigenetics with No Apparent Negative Health Consequences in Rabbit

[EN] Embryo manipulation is a requisite step in assisted reproductive technology (ART). Therefore, it is of great necessity to appraise the safety of ART and investigate the long-term effect, including lipid metabolism, on ART-conceived offspring. Augmenting our ART rabbit model to investigate lipid metabolic outcomes in offspring longitudinally, we detected variations in hepatic DNA methylation ART offspring in the F3 generation for embryonic exposure (multiple ovulation, vitrification and embryo transfer). Through adult liver metabolomics and proteomics, we identified changes mainly related to lipid metabolism (e.g., polyunsaturated fatty acids, steroids, steroid hormone). We also found that DNA methylation analysis was linked to changes in lipid metabolism and apoptosis genes. Nevertheless, these differences did not apparently alter the general health status. Thus, our findings suggest that ART is likely to be a player in embryo epigenetic events related to hepatic homeostasis alteration in adulthood.This research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO), Spain, grant number AGL2014-53405-C2-1-P and by Conselleria d'Educacio, Investigacio, Cultura i Esport, Spain, grant number Prometeo II 2014/036. Ximo Garcia-Dominguez was supported by a research grant from the Ministry of Economy, Industry and Competitiveness of Spain (BES-2015-072429).García-Domínguez, X.; Diretto, G.; Peñaranda, D.; Frusciante, S.; García-Carpintero, V.; Cañizares Sales, J.; Vicente Antón, JS.... (2021). Early Embryo Exposure to Assisted Reproductive Manipulation Induced Subtle Changes in Liver Epigenetics with No Apparent Negative Health Consequences in Rabbit. International Journal of Molecular Sciences. 22(18):1-17. https://doi.org/10.3390/ijms22189716S117221

Effect of embryo vitrification on the steroid biosynthesis of liver tissue in rabbit offspring

[EN] Preimplantation embryo manipulations during standard assisted reproductive technologies (ART) have significant repercussions on offspring. However, few studies to date have investigated the potential long-term outcomes associated with the vitrification procedure. Here, we performed an experiment to unravel the particular effects related to stress induced by embryo transfer and vitrification techniques on offspring phenotype from the foetal period through to prepuberal age, using a rabbit model. In addition, the focus was extended to the liver function at prepuberal age. We showed that, compared to naturally conceived animals (NC), offspring derived after embryo exposure to the transfer procedure (FT) or cryopreservation-transfer procedure (VT) exhibited variation in growth and body weight from foetal life to prepuberal age. Strikingly, we found a nonlinear relationship between FT and VT stressors, most of which were already present in the FT animals. Furthermore, we displayed evidence of variation in liver function at prepuberal age, most of which occurred in both FT and VT animals. The present major novel finding includes a significant alteration of the steroid biosynthesis profile. In summary, here we provide that embryonic manipulation during the vitrification process is linked with embryo phenotypic adaptation detected from foetal life to prepuberal age and suggests that this phenotypic variation may be associated, to a great extent, with the effect of embryo transfer.This research was funded by Conselleria d'Educacio, Investigacio, Cultura i Esport, Spain, grant number AICO/2019/272. Ximo Garcia-Dominguez was supported by a research grant from the Ministry of Economy, Industry and Competitiveness of Spain (BES-2015-072429).Marco-Jiménez, F.; Garcia-Dominguez, X.; Domínguez-Martínez, M.; Viudes-De-Castro, MP.; Diretto, G.; Peñaranda, D.; Vicente Antón, JS. (2020). Effect of embryo vitrification on the steroid biosynthesis of liver tissue in rabbit offspring. International Journal of Molecular Sciences. 21(22):1-17. https://doi.org/10.3390/ijms21228642S1172122Novakovic, B., Lewis, S., Halliday, J., Kennedy, J., Burgner, D. P., Czajko, A., … Saffery, R. (2019). Assisted reproductive technologies are associated with limited epigenetic variation at birth that largely resolves by adulthood. Nature Communications, 10(1). doi:10.1038/s41467-019-11929-9Roseboom, T. J. (2018). Developmental plasticity and its relevance to assisted human reproduction. Human Reproduction, 33(4), 546-552. doi:10.1093/humrep/dey034Fleming, T. P., Watkins, A. J., Velazquez, M. A., Mathers, J. C., Prentice, A. M., Stephenson, J., … Godfrey, K. M. (2018). Origins of lifetime health around the time of conception: causes and consequences. The Lancet, 391(10132), 1842-1852. doi:10.1016/s0140-6736(18)30312-xDulioust, E., Toyama, K., Busnel, M. C., Moutier, R., Carlier, M., Marchaland, C., … Auroux, M. (1995). Long-term effects of embryo freezing in mice. Proceedings of the National Academy of Sciences, 92(2), 589-593. doi:10.1073/pnas.92.2.589Auroux, M., Cerutti, I., Ducot, B., & Loeuillet, A. (2004). Is embryo-cryopreservation really neutral? Reproductive Toxicology, 18(6), 813-818. doi:10.1016/j.reprotox.2004.04.010Vicente, J. S., Saenz-de-Juano, M. D., Jiménez-Trigos, E., Viudes-de-Castro, M. P., Peñaranda, D. S., & Marco-Jiménez, F. (2013). Rabbit morula vitrification reduces early foetal growth and increases losses throughout gestation. Cryobiology, 67(3), 321-326. doi:10.1016/j.cryobiol.2013.09.165Saenz-de-Juano, M. D., Marco-Jimenez, F., Schmaltz-Panneau, B., Jimenez-Trigos, E., Viudes-de-Castro, M. P., Peñaranda, D. S., … Vicente, J. S. (2014). Vitrification alters rabbit foetal placenta at transcriptomic and proteomic level. REPRODUCTION, 147(6), 789-801. doi:10.1530/rep-14-0019Saenz-de-Juano, M. D., Vicente, J. S., Hollung, K., & Marco-Jiménez, F. (2015). Effect of Embryo Vitrification on Rabbit Foetal Placenta Proteome during Pregnancy. PLOS ONE, 10(4), e0125157. doi:10.1371/journal.pone.0125157Berntsen, S., & Pinborg, A. (2018). Large for gestational age and macrosomia in singletons born after frozen/thawed embryo transfer (FET) in assisted reproductive technology (ART). Birth Defects Research, 110(8), 630-643. doi:10.1002/bdr2.1219Maheshwari, A., Pandey, S., Amalraj Raja, E., Shetty, A., Hamilton, M., & Bhattacharya, S. (2017). Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Human Reproduction Update, 24(1), 35-58. doi:10.1093/humupd/dmx031Garcia-Dominguez, X., Vicente, J. S., & Marco-Jiménez, F. (2020). Developmental Plasticity in Response to Embryo Cryopreservation: The Importance of the Vitrification Device in Rabbits. Animals, 10(5), 804. doi:10.3390/ani10050804Kohda, T. (2013). Effects of embryonic manipulation and epigenetics. Journal of Human Genetics, 58(7), 416-420. doi:10.1038/jhg.2013.61Canovas, S., Ross, P. J., Kelsey, G., & Coy, P. (2017). DNA Methylation in Embryo Development: Epigenetic Impact of ART (Assisted Reproductive Technologies). BioEssays, 39(11), 1700106. doi:10.1002/bies.201700106Canovas, S., Ivanova, E., Romar, R., García-Martínez, S., Soriano-Úbeda, C., García-Vázquez, F. A., … Coy, P. (2017). DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids. eLife, 6. doi:10.7554/elife.23670Ivanova, E., Canovas, S., Garcia-Martínez, S., Romar, R., Lopes, J. S., Rizos, D., … Coy, P. (2020). DNA methylation changes during preimplantation development reveal inter-species differences and reprogramming events at imprinted genes. Clinical Epigenetics, 12(1). doi:10.1186/s13148-020-00857-xGarcía-Martínez, S., Sánchez Hurtado, M. A., Gutiérrez, H., Sánchez Margallo, F. M., Romar, R., Latorre, R., … López Albors, O. (2018). Mimicking physiological O2 tension in the female reproductive tract improves assisted reproduction outcomes in pig. MHR: Basic science of reproductive medicine, 24(5), 260-270. doi:10.1093/molehr/gay008Ng, K. Y. B., Mingels, R., Morgan, H., Macklon, N., & Cheong, Y. (2017). In vivo oxygen, temperature and pH dynamics in the female reproductive tract and their importance in human conception: a systematic review. Human Reproduction Update, 24(1), 15-34. doi:10.1093/humupd/dmx028Marchesi, D., Qiao, J., & Feng, H. (2012). Embryo Manipulation and Imprinting. Seminars in Reproductive Medicine, 30(04), 323-334. doi:10.1055/s-0032-1320013Ramos‐Ibeas, P., Heras, S., Gómez‐Redondo, I., Planells, B., Fernández‐González, R., Pericuesta, E., … Gutiérrez‐Adán, A. (2019). Embryo responses to stress induced by assisted reproductive technologies. Molecular Reproduction and Development, 86(10), 1292-1306. doi:10.1002/mrd.23119Vrooman, L. A., & Bartolomei, M. S. (2017). Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse. Reproductive Toxicology, 68, 72-84. doi:10.1016/j.reprotox.2016.07.015Chen, M., & Heilbronn, L. K. (2017). The health outcomes of human offspring conceived by assisted reproductive technologies (ART). Journal of Developmental Origins of Health and Disease, 8(4), 388-402. doi:10.1017/s2040174417000228Duranthon, V., & Chavatte-Palmer, P. (2018). Long term effects of ART: What do animals tell us? Molecular Reproduction and Development, 85(4), 348-368. doi:10.1002/mrd.22970Leibo, S. P., & Sztein, J. M. (2019). Cryopreservation of mammalian embryos: Derivation of a method. Cryobiology, 86, 1-9. doi:10.1016/j.cryobiol.2019.01.007Sparks, A. (2015). Human Embryo Cryopreservation—Methods, Timing, and other Considerations for Optimizing an Embryo Cryopreservation Program. Seminars in Reproductive Medicine, 33(02), 128-144. doi:10.1055/s-0035-1546826De Geyter, C., Calhaz-Jorge, C., Kupka, M. S., Wyns, C., Mocanu, E., Motrenko, T., … Goossens, V. (2020). ART in Europe, 2015: results generated from European registries by ESHRE†. Human Reproduction Open, 2020(1). doi:10.1093/hropen/hoz038Saenz-de-Juano, M., Marco-Jimenez, F., Viudes-de-Castro, M., Lavara, R., & Vicente, J. (2014). Direct Comparison of the Effects of Slow Freezing and Vitrification on Late Blastocyst Gene Expression, Development, Implantation and Offspring of Rabbit Morulae. Reproduction in Domestic Animals, 49(3), 505-511. doi:10.1111/rda.12320Garcia-Dominguez, X., Marco-Jiménez, F., Peñaranda, D. S., & Vicente, J. S. (2020). Long-Term Phenotypic and Proteomic Changes Following Vitrified Embryo Transfer in the Rabbit Model. Animals, 10(6), 1043. doi:10.3390/ani10061043Lavara, R., Baselga, M., Marco-Jiménez, F., & Vicente, J. S. (2015). Embryo vitrification in rabbits: Consequences for progeny growth. Theriogenology, 84(5), 674-680. doi:10.1016/j.theriogenology.2015.04.025Lavara, R., Baselga, M., Marco-Jiménez, F., & Vicente, J. S. (2014). Long-term and transgenerational effects of cryopreservation on rabbit embryos. Theriogenology, 81(7), 988-992. doi:10.1016/j.theriogenology.2014.01.030Garcia-Dominguez, X., Marco-Jiménez, F., Peñaranda, D. S., Diretto, G., García-Carpintero, V., Cañizares, J., & Vicente, J. S. (2020). Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer. Scientific Reports, 10(1). doi:10.1038/s41598-020-68195-9Feuer, S., & Rinaudo, P. (2016). From Embryos to Adults: A DOHaD Perspective on In Vitro Fertilization and Other Assisted Reproductive Technologies. Healthcare, 4(3), 51. doi:10.3390/healthcare4030051Zandstra, H., Brentjens, L. B. P. M., Spauwen, B., Touwslager, R. N. H., Bons, J. A. P., Mulder, A. L., … Van Montfoort, A. P. A. (2018). Association of culture medium with growth, weight and cardiovascular development of IVF children at the age of 9 years. Human Reproduction, 33(9), 1645-1656. doi:10.1093/humrep/dey246Chen, L., Yang, T., Zheng, Z., Yu, H., Wang, H., & Qin, J. (2018). Birth prevalence of congenital malformations in singleton pregnancies resulting from in vitro fertilization/intracytoplasmic sperm injection worldwide: a systematic review and meta-analysis. Archives of Gynecology and Obstetrics, 297(5), 1115-1130. doi:10.1007/s00404-018-4712-xZhang, W. Y., Selamet Tierney, E. S., Chen, A. C., Ling, A. Y., Fleischmann, R. R., & Baker, V. L. (2019). Vascular Health of Children Conceived via In Vitro Fertilization. The Journal of Pediatrics, 214, 47-53. doi:10.1016/j.jpeds.2019.07.033Guo, X.-Y., Liu, X.-M., Jin, L., Wang, T.-T., Ullah, K., Sheng, J.-Z., & Huang, H.-F. (2017). Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: a systematic review and meta-analysis. Fertility and Sterility, 107(3), 622-631.e5. doi:10.1016/j.fertnstert.2016.12.007Feuer, S. K., Liu, X., Donjacour, A., Simbulan, R., Maltepe, E., & Rinaudo, P. (2017). Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro. Reproduction, 153(1), 107-122. doi:10.1530/rep-16-0473Feuer, S. K., & Rinaudo, P. F. (2017). Physiological, metabolic and transcriptional postnatal phenotypes ofin vitrofertilization (IVF) in the mouse. Journal of Developmental Origins of Health and Disease, 8(4), 403-410. doi:10.1017/s204017441700023xEcker, D. J., Stein, P., Xu, Z., Williams, C. J., Kopf, G. S., Bilker, W. B., … Schultz, R. M. (2004). Long-term effects of culture of preimplantation mouse embryos on behavior. Proceedings of the National Academy of Sciences, 101(6), 1595-1600. doi:10.1073/pnas.0306846101Fauque, P., Mondon, F., Letourneur, F., Ripoche, M.-A., Journot, L., Barbaux, S., … Vaiman, D. (2010). In Vitro Fertilization and Embryo Culture Strongly Impact the Placental Transcriptome in the Mouse Model. PLoS ONE, 5(2), e9218. doi:10.1371/journal.pone.0009218Fernandez-Gonzalez, R., Ramirez, M. A., Pericuesta, E., Calle, A., & Gutierrez-Adan, A. (2010). Histone Modifications at the Blastocyst Axin1Fu Locus Mark the Heritability of In Vitro Culture-Induced Epigenetic Alterations in Mice1. Biology of Reproduction, 83(5), 720-727. doi:10.1095/biolreprod.110.084715Fernandez-Gonzalez, R., Moreira, P., Bilbao, A., Jimenez, A., Perez-Crespo, M., Ramirez, M. A., … Gutierrez-Adan, A. (2004). Long-term effect of in vitro culture of mouse embryos with serum on mRNA expression of imprinting genes, development, and behavior. Proceedings of the National Academy of Sciences, 101(16), 5880-5885. doi:10.1073/pnas.0308560101Winick, M., & Noble, A. (1965). Quantitative changes in DNA, RNA, and protein during prenatal and postnatal growth in the rat. Developmental Biology, 12(3), 451-466. doi:10.1016/0012-1606(65)90009-6Saenz-de-Juano, M. D., Marco-Jiménez, F., & Vicente, J. S. (2016). Embryo transfer manipulation cause gene expression variation in blastocysts that disrupt implantation and offspring rates at birth in rabbit. European Journal of Obstetrics & Gynecology and Reproductive Biology, 207, 50-55. doi:10.1016/j.ejogrb.2016.10.049Delle Piane, L., Lin, W., Liu, X., Donjacour, A., Minasi, P., Revelli, A., … Rinaudo, P. F. (2010). Effect of the method of conception and embryo transfer procedure on mid-gestation placenta and fetal development in an IVF mouse model. Human Reproduction, 25(8), 2039-2046. doi:10.1093/humrep/deq165Wale, P. L., & Gardner, D. K. (2015). The effects of chemical and physical factors on mammalian embryo culture and their importance for the practice of assisted human reproduction. Human Reproduction Update, 22(1), 2-22. doi:10.1093/humupd/dmv034Charni-Natan, M., Aloni-Grinstein, R., Osher, E., & Rotter, V. (2019). Liver and Steroid Hormones—Can a Touch of p53 Make a Difference? Frontiers in Endocrinology, 10. doi:10.3389/fendo.2019.00374Yakar, S., Liu, J.-L., Stannard, B., Butler, A., Accili, D., Sauer, B., & LeRoith, D. (1999). Normal growth and development in the absence of hepatic insulin-like growth factor I. Proceedings of the National Academy of Sciences, 96(13), 7324-7329. doi:10.1073/pnas.96.13.7324Juul, A. (2003). Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Growth Hormone & IGF Research, 13(4), 113-170. doi:10.1016/s1096-6374(03)00038-8Miles, H. L., Hofman, P. L., Peek, J., Harris, M., Wilson, D., Robinson, E. M., … Cutfield, W. S. (2007). In Vitro Fertilization Improves Childhood Growth and Metabolism. The Journal of Clinical Endocrinology & Metabolism, 92(9), 3441-3445. doi:10.1210/jc.2006-2465Belva, F., Bonduelle, M., Provyn, S., Painter, R. C., Tournaye, H., Roelants, M., & De Schepper, J. (2018). Metabolic Syndrome and Its Components in Young Adults Conceived by ICSI. International Journal of Endocrinology, 2018, 1-8. doi:10.1155/2018/8170518Fournier, N., Atger, V., Paul, J.-L., Sturm, M., Duverger, N., Rothblat, G. H., & Moatti, N. (2000). Human ApoA-IV Overexpression in Transgenic Mice Induces cAMP-Stimulated Cholesterol Efflux From J774 Macrophages to Whole Serum. Arteriosclerosis, Thrombosis, and Vascular Biology, 20(5), 1283-1292. doi:10.1161/01.atv.20.5.1283Liang, Y., Jiang, X.-C., Liu, R., Liang, G., Beyer, T. P., Gao, H., … Cao, G. (2004). Liver X Receptors (LXRs) Regulate Apolipoprotein AIV-Implications of the Antiatherosclerotic Effect of LXR Agonists. Molecular Endocrinology, 18(8), 2000-2010. doi:10.1210/me.2003-0477Lin, Q., Cao, Y., & Gao, J. (2015). Decreased expression of the APOA1–APOC3–APOA4 gene cluster is associated with risk of Alzheimer’s disease. Drug Design, Development and Therapy, 5421. doi:10.2147/dddt.s89279Qin, W., Li, X., Xie, L., Li, S., Liu, J., Jia, L., … Chen, Z. (2016). A long non-coding RNA,APOA4-AS, regulatesAPOA4expression depending on HuR in mice. Nucleic Acids Research, 44(13), 6423-6433. doi:10.1093/nar/gkw341Leese, H. J., Guerif, F., Allgar, V., Brison, D. R., Lundin, K., & Sturmey, R. G. (2016). Biological optimization, the Goldilocks principle, and how much islagomin the preimplantation embryo. Molecular Reproduction and Development, 83(9), 748-754. doi:10.1002/mrd.22684Kohda, T., & Ishino, F. (2013). Embryo manipulation via assisted reproductive technology and epigenetic asymmetry in mammalian early development. Philosophical Transactions of the Royal Society B: Biological Sciences, 368(1609), 20120353. doi:10.1098/rstb.2012.0353Garcia-Dominguez, X., Juarez, J. D., Vicente, J. S., & Marco-Jiménez, F. (2020). Impact of embryo technologies on secondary sex ratio in rabbit. Cryobiology, 97, 60-65. doi:10.1016/j.cryobiol.2020.10.008Viudes-de-Castro, M. P., Marco-Jiménez, F., Cedano-Castro, J. I., & Vicente, J. S. (2017). Effect of corifollitropin alfa supplemented with or without LH on ovarian stimulation and embryo viability in rabbit. Theriogenology, 98, 68-74. doi:10.1016/j.theriogenology.2017.05.005Marco-Jiménez, F., Lavara, R., Jiménez-Trigos, E., & Vicente, J. S. (2013). In vivo development of vitrified rabbit embryos: Effects of vitrification device, recipient genotype, and asynchrony. Theriogenology, 79(7), 1124-1129. doi:10.1016/j.theriogenology.2013.02.008Vicente, J.-S., Viudes-de-Castro, M.-P., & García, M.-L. (1999). 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Chaotic, memory and cooling rate effects in spin glasses: Is the Edwards-Anderson model a good spin glass?

We investigate chaotic, memory and cooling rate effects in the three dimensional Edwards-Anderson model by doing thermoremanent (TRM) and AC susceptibility numerical experiments and making a detailed comparison with laboratory experiments on spin glasses. In contrast to the experiments, the Edwards-Anderson model does not show any trace of re-initialization processes in temperature change experiments (TRM or AC). A detailed comparison with AC relaxation experiments in the presence of DC magnetic field or coupling distribution perturbations reveals that the absence of chaotic effects in the Edwards-Anderson model is a consequence of the presence of strong cooling rate effects. We discuss possible solutions to this discrepancy, in particular the smallness of the time scales reached in numerical experiments, but we also question the validity of the Edwards-Anderson model to reproduce the experimental results.Comment: 17 pages, 10 figures. The original version of the paper has been split in two parts. The second part is now available as cond-mat/010224

Comparison of two techniques for the morphometry study on gilthead seabream (Sparus aurata) spermatozoa and evaluation of changes induced by cryopreservation

[EN] The development of powerful software has made possible spermatozoa morphology studies. However, some problems have emerged in relation to protocol standardization to compare results from different laboratories. This study was carried out to compare two techniques commonly used (staining vs phase contrast technique) for the morphometry study of gilthead sea bream spermatozoa using an integrated sperm analysis system (ISAS). Spermatozoa morphometry values were significantly affected by the technique used, and phase contrast technique was found to be the more accurate method, showing lower coefficients of variation on spermatozoa morphometry parameters measurements. Moreover, it has been shown that cryopreservation process produces damage in gilthead sea bream spermatozoa, causing negative effects in sperm parameters as spermatozoa morphometry (a decrease in cell volume), motility (from 95 to 68% motile cells) and viability (from 95 to 87% of live cells), being the addition of freezing medium containing cryoprotectant (DMSO) an important factor that caused the morphometry changes. (C) 2012 Elsevier Inc. All rights reserved.This work was financed by the Spanish Ministry of Science and Innovation (MICINN; AGL2007-64040-C03-00, Project SELECTBREAM). V. Gallego and I. Mazzeo were supported by predoctoral scholarships financed by the Spanish MICINN and Generalitat Valenciana, respectively. D.S. Penaranda had a postdoctoral grant from UPV.Gallego Albiach, V.; Peñaranda, D.; Marco Jiménez, F.; Mazzeo, I.; Pérez Igualada, LM.; Asturiano Nemesio, JF. (2012). Comparison of two techniques for the morphometry study on gilthead seabream (Sparus aurata) spermatozoa and evaluation of changes induced by cryopreservation. Theriogenology. 77(6):1078-1087. https://doi.org/10.1016/j.theriogenology.2011.10.010S1078108777

Disorder Induced Phase Transition in a Random Quantum Antiferromagnet

A two-dimensional Heisenberg model with random antiferromagnetic nearest-neighbor exchange is studied using quantum Monte Carlo techniques. As the strength of the randomness is increased, the system undergoes a transition from an antiferromagnetically ordered ground state to a gapless disordered state. The finite-size scaling of the staggered structure factor and susceptibility is consistent with a dynamic exponent $z = 2$.Comment: Revtex 3.0, 10 pages + 5 postscript figures available upon request, UCSBTH-94-1