Periodic Reporting for period 1 - Alloem (Maternal immune response to allogeneic embryos)
Reporting period: 2020-07-01 to 2022-06-30
High embryonic mortality at the peri-implantation period (70%) is accounted after pig embryo transfer (ET), which is almost double than that of natural breeding or artificial insemination (AI). Since pregnancy is an interesting immunological paradox, our starting hypothesis is that the mechanisms regulating the maternal immune response to the embryos may be less efficient in the case of ET pregnancies, where the transferred embryos are allogeneic (e.g. contain paternal and maternal material unrelated to the recipient mother) than after natural breeding or AI, where only paternal material is unrelated to the mother (semi-allogeneic). This difference could be behind the increased embryonic death. The project will study transcriptomic and cytokine changes of porcine endometrial tissue in the presence of semi-allogeneic and allogeneic embryos during the peri-implantation period and also in the placenta of healthy and arrested fetuses. The results of the project will unveil mechanisms behind embryo-maternal dialogue. This fact is relevant in view of the necessary implementation of emergent breeding technologies, as embryo transfer (ET), for supporting sustainability and competitiveness of the European pig sector. EU is currently second biggest pig producer in the world and the largest exporter of antibiotic- and residue-free pig products derived from animals raised on highest welfare standards and with the highest genetic value. The understanding of embryo-maternal dialogue under allogeneic environments might be determinant to implement new strategies to increase the reproductive performance after ET not only in pigs but also, comparatively, in other livestock species and even in humans, where the use of donor oocytes for IVF is currently increasing. This project, with a focus on pregnancy immunological regulation, is of utmost interest for the EU goals, contributing to determine which factors still jeopardize full fertility and prolificacy when applying ET technology.
All the scientific publications derived from this project have been published in Open Access and have been uploaded to the Digitala Vetenskapliga Arkivet (DIVA) repository at Linköping University making them accessible to everyone. In addition, sequencing data has also been made publicly available by uploading it to the international open access Sequence Read Archive (SRA) repository. In all instances, EU funding through the Horizon 2020 MSCAIF scheme has been acknowledged.
During the course of the project the Fellow has also been able to work in collaboration to other researchers in the host institution, as well as prior collaborators of the Fellow. This has led to the publication of 23 papers, including the ones directly derived from this project. Selected 10 publications:
Martinez CA, Alvarez-Rodriguez M, Wright D, Rodriguez-Martinez H. 2020. Does the Pre-Ovulatory Pig Oviduct Rule Sperm Capacitation In Vivo Mediating Transcriptomics of Catsper Channels? IJMS, 21:1840.
Álvarez-Rodríguez M*∞, Martinez CA∞, Wright D, Rodríguez-Martinez H. 2020. Role of semen and seminal plasma in inducing large-scale genomic changes in the female porcine peri-ovulatory tract. Sci Rep, 10(1):5061.
Martinez CA, Rubér M, Rodriguez-Martinez H, Alvarez-Rodriguez M. 2020. Pig pregnancies after transfer of allogeneic embryos show a dysregulated endometrial/placental cytokine balance: a novel clue for embryo death? Biomolecules. 10(4):554. DOI: 10.3390/biom10040554.
Cambra JM, Jauregui A, Alvarez-Rodriguez M, Parrilla I, Martinez EA, Gil MA, Cuello C, Rodriguez-Martinez H, Martinez CA. 2020. Allogeneic embryos dysregulatе leukemia inhibitory factor (LIF) and its receptor in the porcine endometrium during implantation. Frontiers in Veterinary Sciences, 7:611598.
Martinez CA, Marteinsdottir I, Josefsson A, Sydsjö G, Theodorsson E, Rodriguez-Martinez H. 2020. Expression of stress-mediating genes is increased in term placentas of women with chronic self-perceived anxiety and depression. Genes, 11(8):E869.
Álvarez-Rodríguez M*∞, Martinez CA∞, Wright D, Rodríguez-Martinez H. 2020. Does the Act of Copulation per se, without Considering Seminal Deposition, Change the Expression of Genes in the Porcine Female Genital Tract? IJMS, 21(15): 5477.
Martinez CA, Alvarez-Rodriguez M, Casado-Bedmar M, Rodriguez-Martinez H. 2021. In Vitro Maturation of Cumulus–Oocyte Complexes and In Vitro Sperm Capacitation Significantly Increase the Expression and Enhance the Location of the CXCL12 and CXCR4 Anchoring Attractant Complex in Pigs. Animals, 11(1):153.
Rodriguez-Martinez H, Roca J, Alvarez-Rodriguez M, Martinez CA. 2021. How does the boar epididymis regulate the emission of fertile spermatozoa? Animal Reproduction Science, 106829.
Martinez CA, Cambra JM, Lucas X, Ferreira-Dias G, Rodriguez-Martinez H, Gil MA, Martinez EA, Cuello C, Parrilla I. 2021. Intrauterine Infusion of TGF-β1 Prior to Insemination, Alike Seminal Plasma, Influences Endometrial Cytokine Responses but Does Not Impact the Timing of the Progression of Pre-Implantation Pig Embryo Development. Biology, 10(2), 159.
Martinez CA, Marteinsdottir I, Josefsson A, Sydsjö G, Theodorsson E, Rodriguez-Martinez H. 2022. Prenatal stress, anxiety and depression alter transcripts, proteins and pathways associated with immune responses at the maternal-fetal interface†. Biol Reprod. 2022 Mar 19;106(3):449-462. doi: 10.1093/biolre/ioab232.
Martinez CA, Rodriguez‐Martinez H. 2022. Context is key: Maternal immune responses to pig allogeneic embryos. Molecular Reproductiona & Development. https://doi.org/10.1002/mrd.23624(opens in new window).
Martinez CA, Alvarez-Rodriguez M, Rodriguez-Martinez H. 2022. A decreased expression of Interferon Stimulated Genes in peri-implantation endometrium of embryo transfer recipient sows could contribute to embryo death. Animal. Accepted.
During the course of the project the Fellow has also been able to work in collaboration to other researchers in the host institution, as well as prior collaborators of the Fellow. This has led to the publication of 23 papers, including the ones directly derived from this project. Selected 10 publications:
Martinez CA, Alvarez-Rodriguez M, Wright D, Rodriguez-Martinez H. 2020. Does the Pre-Ovulatory Pig Oviduct Rule Sperm Capacitation In Vivo Mediating Transcriptomics of Catsper Channels? IJMS, 21:1840.
Álvarez-Rodríguez M*∞, Martinez CA∞, Wright D, Rodríguez-Martinez H. 2020. Role of semen and seminal plasma in inducing large-scale genomic changes in the female porcine peri-ovulatory tract. Sci Rep, 10(1):5061.
Martinez CA, Rubér M, Rodriguez-Martinez H, Alvarez-Rodriguez M. 2020. Pig pregnancies after transfer of allogeneic embryos show a dysregulated endometrial/placental cytokine balance: a novel clue for embryo death? Biomolecules. 10(4):554. DOI: 10.3390/biom10040554.
Cambra JM, Jauregui A, Alvarez-Rodriguez M, Parrilla I, Martinez EA, Gil MA, Cuello C, Rodriguez-Martinez H, Martinez CA. 2020. Allogeneic embryos dysregulatе leukemia inhibitory factor (LIF) and its receptor in the porcine endometrium during implantation. Frontiers in Veterinary Sciences, 7:611598.
Martinez CA, Marteinsdottir I, Josefsson A, Sydsjö G, Theodorsson E, Rodriguez-Martinez H. 2020. Expression of stress-mediating genes is increased in term placentas of women with chronic self-perceived anxiety and depression. Genes, 11(8):E869.
Álvarez-Rodríguez M*∞, Martinez CA∞, Wright D, Rodríguez-Martinez H. 2020. Does the Act of Copulation per se, without Considering Seminal Deposition, Change the Expression of Genes in the Porcine Female Genital Tract? IJMS, 21(15): 5477.
Martinez CA, Alvarez-Rodriguez M, Casado-Bedmar M, Rodriguez-Martinez H. 2021. In Vitro Maturation of Cumulus–Oocyte Complexes and In Vitro Sperm Capacitation Significantly Increase the Expression and Enhance the Location of the CXCL12 and CXCR4 Anchoring Attractant Complex in Pigs. Animals, 11(1):153.
Rodriguez-Martinez H, Roca J, Alvarez-Rodriguez M, Martinez CA. 2021. How does the boar epididymis regulate the emission of fertile spermatozoa? Animal Reproduction Science, 106829.
Martinez CA, Cambra JM, Lucas X, Ferreira-Dias G, Rodriguez-Martinez H, Gil MA, Martinez EA, Cuello C, Parrilla I. 2021. Intrauterine Infusion of TGF-β1 Prior to Insemination, Alike Seminal Plasma, Influences Endometrial Cytokine Responses but Does Not Impact the Timing of the Progression of Pre-Implantation Pig Embryo Development. Biology, 10(2), 159.
Martinez CA, Marteinsdottir I, Josefsson A, Sydsjö G, Theodorsson E, Rodriguez-Martinez H. 2022. Prenatal stress, anxiety and depression alter transcripts, proteins and pathways associated with immune responses at the maternal-fetal interface†. Biol Reprod. 2022 Mar 19;106(3):449-462. doi: 10.1093/biolre/ioab232.
Martinez CA, Rodriguez‐Martinez H. 2022. Context is key: Maternal immune responses to pig allogeneic embryos. Molecular Reproductiona & Development. https://doi.org/10.1002/mrd.23624(opens in new window).
Martinez CA, Alvarez-Rodriguez M, Rodriguez-Martinez H. 2022. A decreased expression of Interferon Stimulated Genes in peri-implantation endometrium of embryo transfer recipient sows could contribute to embryo death. Animal. Accepted.
Because of all the merits achieved the Fellow was able to obtain a research grant from the Spanish government “Juan de la Cierva-Incoproracion” which will further promote her establishment as an independent researcher. Additionally, the new skills and knowledge acquired during her fellowship will be of great interest to companies working in the field of fertility (e.g. human assisted reproductive clinics), as well as for genetic pig companies. Through the implementation of the project, the host institution has also benefited an increase in research output and an expansion of the international network of collaborators for European and international cooperation. In addition, it is the ultimate goal of this Fellow to ensure that the results obtained from this study can be applied at farm level. Because pig production constitute such a high agricultural output for the EU, this will translate into a direct impact on improving the competitiveness of European farms, hence favouring sustained economy and growth, and the development of rural communities.