Dr. Carlos Simón Vallés

Principal Investigator
Research Group on Reproductive Medicine

Presentation


Carlos Simón is a Professor of Obstetrics and Gynecology at the University of Valencia, an Adjunct Professor at BIDMC Harvard University, USA, and President of the Carlos Simón Foundation.

His main interest lies in understanding the process of human embryo implantation during the preconception period, considering the embryo, the maternal endometrium, and the cross-talk between them as key elements using different scientific approaches.

His group identified the transcriptomic signature of human endometrial receptivity using microarray technology (PMID: 20619403) and its confirmation by single-cell RNA sequencing (PMID: 32929266). The clinical translation of this work resulted in the creation of the Endometrial Receptivity Analysis (ERA) for the diagnosis of the personalized implantation window in infertile patients. His team provided evidence of a decidualization defect in the endometrium of women with severe preeclampsia, a pathology detectable at the time of delivery and that persists for years (PMC: 5635883), also discovering the fingerprint that encodes this defect (PMC: 8553341). In addition, they demonstrated that the human uterine cavity is not sterile, by identifying the existence of the endometrial microbiome (PMID: 27717732) and its functional implications in pregnancy outcome in infertile patients (PMC: 8725275). Furthermore, they investigated the existence and proof of concept of human endometrial stem cells. Today, these findings are applied in the first advanced cell therapy for Asherman’s syndrome ((PMID: 27005892), (Clinical Trial, EudraCT Reference: 2016-003975-23)).

For the human embryo, he created a predictive model of aneuploidy in early embryonic development revealed by single-cell analysis (PMID: 26151134), deciphered the clinical impact of embryonic mosaicism (PMCID: PMC8715143), and discovered the origin and composition of cell-free DNA of human embryos (PMID: 29471395) and its clinical translation (PMID: 32470458)). His team derived, characterized, and registered 10 human embryonic stem cell lines in the Spanish National Cell Bank. (PMID: 20018958). His pioneering work in this field made possible the creation of the Valencia Node of the Spanish Cell Bank in 2004. Finally, the cross-talk between the maternal endometrium and the embryo has been addressed (PMID: 29390102) by discovering that maternal microRNAs (miRNAs) could act as a transcriptomic modifier of the preimplantation embryo (PMID: 26395145).

His commitment to research excellence is demonstrated by the publication of 539 articles in international peer-reviewed journals. His articles have received a total of 51,190 citations. His Google Scholar is 129. He is the editor of 21 books in English, Spanish, and Portuguese, and supervisor of 40 doctoral theses. His work has been awarded by several scientific societies, including SGI/SRI and institutions such as the Rey Jaime I Medical Research Award 2011, the ASRM Distinguished Research Award 2016, the Lilly Foundation Biomedical Research Award 2021, and the RANME Translational Medical Research Award 2023.

https://www.ncbi.nlm.nih.gov/sites/myncbi/1j_Xa5ecX9MAF/bibliography/43442561/public/?sort=date&direction=descending

Google Scholar: https://scholar.google.es/citations?user=nA_MhRMAAAAJ&hl=es

ORCID: http://orcid.org/0000-0003-0902-9531

Personal webpage: www.carlos-simon.com

Dr. Carlos Simón Valles
Principal
Investigator
Dr. Carlos Simón Vallés

carlos.simon@uv.es; csimon@fundacioncarlossimon.com

Publications
Effect of aging on the human myometrium at single-cell resolution. Punzon-Jimenez P, Machado-Lopez A, Perez-Moraga R, Llera-Oyola J, Grases D, Galvez-Viedma M, Sibai M, Satorres-Perez E, Lopez-Agullo S, Badenes R, Ferrer-Gomez C, Porta-Pardo E, Roson B, Simon C, Mas A. Nature Communications. 2024 Jan 31;15(1):945. doi: 10.1038/s41467-024-45143-z. PMID: 38296945

Normothermic machine perfusion systems: where do we go from here?. Lopez-Martinez S, Simon C, Santamaria X. Transplantation. 2024 Jan 1;108(1):22-44. doi: 10.1097/TP.0000000000004573. PMID: 37026713

Decoding the endometrial niche of Asherman’s Syndrome at single-cell resolution. Santamaria X, Roson B, Perez-Moraga R, Venkatesan N, Pardo-Figuerez M, Gonzalez-Fernandez J, Llera-Oyola J, Fernandez E, Moreno I, Salumets A, Vankelecom H, Vilella F, Simon C. Nature Communications. 2023 Sep 21;14(1):5890. doi: 10.1038/s41467-023-41656-1. PMID: 37735465

Human embryo live imaging reveals nuclear DNA shedding during blastocyst expansion and biopsy. Domingo-Muelas A, Skory RM, Moverley AA, Ardestani G, Pomp O, Rubio C, Tetlak P, Hernandez B, Rhon-Calderon EA, Navarro-Sanchez L, Garcia-Pascual CM, Bissiere S, Bartolomei MS, Sakkas D, Simon C, Plachta N. Cell. 2023 Jul 20;186(15):3166-3181.e18. doi: 10.1016/j.cell.2023.06.003. PMID: 37413989

Improved clinical utility of preimplantation genetic testing through the integration of ploidy and common pathogenic microdeletions analyses. Caroselli S, Figliuzzi M, Picchetta L, Cogo F, Zambon P, Pergher I, Girardi L, Patassini C, Poli M, Bakalova D, Cimadomo D, Findikli N, Coban O, Serdarogullari M, Favero F, Bortolato S, Anastasi A, Capodanno F, Gallinelli A, Brancati F, Rienzi L, Ubaldi FM, Jimenez Almazan J, Blesa Jarque D, Miravet Valenciano J, Rubio C, Simon C, Capalbo A. Human Reproduction. 2023 Apr 3;38(4):762-775. doi: 10.1093/humrep/dead033. PMID: 36824049

Single-cell multi-omic analysis profiles defective genome activation and epigenetic reprogramming associated with human pre-implantation embryo arrest. Hernandez Mora JR, Buhigas C, Clark S, Del Gallego Bonilla R, Daskeviciute D, Monteagudo-Sanchez A, Poo-Llanillo ME, Medrano JV, Simon C, Meseguer M, Kelsey G, Monk D. Cell Reports. 2023 Feb 9;42(2):112100. doi: 10.1016/j.celrep.2023.112100. PMID: 36763500

The human periconceptional maternal-embryonic space in health and disease. Moreno I, Capalbo A, Mas A, Garrido-Gomez T, Roson B, Poli M, Dimitriadis E, Santamaria X, Vilella F, Simon C. Physiological Reviews. 2023 Jul 1;103(3):1965-2038. doi: 10.1152/physrev.00050.2021. PMID: 36796099

The role of extracellular vesicles in intercellular communication in human reproduction. Gonzalez Fernandez J, Moncayo Arlandi J, Ochando A, Simon C, Vilella F. Clinical Science. 2023 Feb 14;137(3):281-301. doi: 10.1042/CS20220793. PMID: 36762584

The use of copy number loads to designate mosaicism in blastocyst stage PGT-A cycles: fewer is better. Girardi L, Figliuzzi M, Poli M, Serdarogullari M, Patassini C, Caroselli S, Pergher I, Cogo F, Coban O, Boynukalin F, Bahceci M, Navarro R, Rubio C, Findikli N, Simon C, Capalbo A. Human Reproduction. 2023 May 2;38(5):982-991. doi: 10.1093/humrep/dead049. PMID: 36928183

Two studies in the same center, on the same patient population and topic, but with different results. Is the experimental design to blame?. Simon C, Ruiz-Alonso M, Gomez C, Valbuena D. Fertility and Sterility. 2023 Mar;119(3):514-515. doi: 10.1016/j.fertnstert.2022.11.019. PMID: 36462548

Updates on preimplantation embryo research. Bissiere S, Hernandez B, Rubio C, Simon C, Plachta N. Fertility and Sterility. 2023 Sep;120(3 Pt 1):467-472. doi: 10.1016/j.fertnstert.2023.04.039. PMID: 37150393

Vertical transmission of maternal DNA through extracellular vesicles associates with altered embryo bioenergetics during the periconception period. Bolumar D, Moncayo-Arlandi J, Gonzalez-Fernandez J, Ochando A, Moreno I, Monteagudo-Sanchez A, Marin C, Diez A, Fabra P, Checa M, Espinos J, Gardner D, Simon C, Vilella F. eLife. 2023 Dec 27:12:RP88008. doi: 10.7554/eLife.88008. PMID: 38149847

Avoid mixing apples and oranges: blastocysts diagnosed with uniform whole chromosome aneuploidies are reproductively incompetent and their transfer is harmful. Capalbo A, Cimadomo D, Rienzi L, Garcia-Velasco J, Simon C, Ubaldi F. Human Reproduction. 2022 Aug 25;37(9):2213-2214. doi: 10.1093/humrep/deac149. PMID: 35796677

Cell-free fetal DNA testing performance and fetal fraction estimation are not affected in ART-conceived pregnancies. Balaguer N, Mateu-Brull E, Gomez-Lopez M, Simon C, Milan M. Human Reproduction. 2022 Nov 24;37(12):2743-2756. doi: 10.1093/humrep/deac217. PMID: 36223600

Decidualization resistance in the origin of preeclampsia. Garrido Gomez T, Castillo Marco N, Cordero T, Simon Valles C. American Journal of Obstetrics and Gynecology. 2022 Feb;226(2S):S886-S894. doi: 10.1016/j.ajog.2020.09.039. PMID: 33007270

Do clinical outcomes differ for day-5 versus day-6 single embryo transfers controlled for endometrial factor?. Stankewicz T, Ruiz Alonso M, Soler Ibanez M, Simon C, Valbuena D. Reproductive Biomedicine Online. 2022 Mar;44(3):478-485. doi: 10.1016/j.rbmo.2021.11.010. PMID: 35125295

Endometrial factor testing is a useful tool in clinical infertility management. Simon C. Reproductive Biomedicine Online. 2022 Jun;44(6):953-960. doi: 10.1016/j.rbmo.2021.12.014. PMID: 35221254

Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Moreno I, Garcia-Grau I, Perez-Villaroya D, Gonzalez-Monfort M, Bahceci M, Barrionuevo MJ, Taguchi S, Puente E, Dimattina M, Lim MW, Meneghini G, Aubuchon M, Leondires M, Izquierdo A, Perez-Olgiati M, Chavez A, Seethram K, Bau D, Gomez C, Valbuena D, Vilella F, Simon C. Microbiome. 2022 Jan 4;10(1):1. doi: 10.1186/s40168-021-01184-w. PMID: 34980280

Follicular activation in women previously diagnosed with poor ovarian response: a randomized, controlled trial. Diaz-Garcia C, Herraiz S, Pamplona L, Subira J, Soriano M, Simon C, Seli E, Pellicer A. Fertility and Sterility. 2022 Apr;117(4):747-755. doi: 10.1016/j.fertnstert.2021.12.034. PMID: 35367015

Human endometrial cell-type-specific RNA sequencing provides new insights into the embryo-endometrium interplay. Koel M, Krjutskov K, Saare M, Samuel K, Lubenets D, Katayama S, Einarsdottir E, Vargas E, Sola-Leyva A, Lalitkumar P, Gemzell-Danielsson K, Blesa D, Simon C, Lanner F, Kere J, Salumets A, Altmae S. Human Reproduction Open. 2022 Oct 13;2022(4):hoac043. doi: 10.1093/hropen/hoac043. PMID: 36339249

Individual participant data meta-analysis of trials comparing frozen versus fresh embryo transfer strategy (INFORM): a protocol. Wang R, McLernon D, Lai S, Showell M, Chen Z, Wei D, Legro R, Wang Z, Sun Y, Wu K, Vuong L, Hardy P, Pinborg A, Stormlund S, Santamaria X, Simon C, Blockeel C, Mol F, Ferraretti A, Shapiro B, Garner F, Li R, Venetis C, Mol B, Bhattacharya S, Maheshwari A. BMJ Open. 2022 Jul 18;12(7):e062578. doi: 10.1136/bmjopen-2022-062578. PMID: 35851030

Integrative genomic and transcriptomic profiling reveals a differential molecular signature in uterine leiomyoma versus leiomyosarcoma. Machado Lopez A, Alonso R, Lago V, Jimenez Almazan J, Garcia M, Monleon J, Lopez S, Barcelo F, Torroba A, Ortiz S, Domingo S, Simon C, Mas A. International Journal of Molecular Sciences. 2022 Feb 16;23(4):2190. doi: 10.3390/ijms23042190. PMID: 35216305

Maternal exome analysis for the diagnosis of oocyte maturation defects and early embryonic developmental arrest. Capalbo A, Buonaiuto S, Figliuzzi M, Damaggio G, Girardi L, Caroselli S, Poli M, Patassini C, Cetinkaya M, Yuksel B, Azad A, Grondahl M, Hoffmann E, Simon C, Colonna V, Kahraman S. Reproductive Biomedicine Online. 2022 Sep;45(3):508-518. doi: 10.1016/j.rbmo.2022.05.009. PMID: 35798635

Molecular Management of High-Grade Serous Ovarian Carcinoma. Punzon-Jimenez P, Lago V, Domingo S, Simon C, Mas A. International Journal of Molecular Sciences. 2022 Nov 9;23(22):13777. doi: 10.3390/ijms232213777. PMID: 36430255

Non-invasive preimplantation genetic testing for aneuploidies: an update. Navarro-Sanchez L, Garcia-Pascual C, Rubio C, Simon C. Reproductive Biomedicine Online. 2022 May;44(5):817-828. doi: 10.1016/j.rbmo.2022.01.012. PMID: 35307298

PGDIS position statement on the transfer of mosaic embryos 2021. Leigh D, Cram D, Rechitsky S, Handyside A, Wells D, Munne S, Kahraman S, Grifo J, Katz-Jaffe M, Rubio C, Viotti M, Forman E, Xu K, Gordon T, Madjunkova S, Qiao J, Chen Z, Harton G, Gianaroli L, Simon C, Scott R, Simpson J, Kuliev A. Reproductive Biomedicine Online. 2022 Jul;45(1):19-25. doi: 10.1016/j.rbmo.2022.03.013. PMID: 35523707

Should patients be screened for chronic endometritis before assisted reproductive technology?. Cicinelli E, McQueen DB, Huepfel B, Vitagliano A, Moreno I, Simon C, Pirtea P, Scott RTJ, Bellavia M, de Ziegler D. Fertility and Sterility. 2022 Oct;118(4):639-652. doi: 10.1016/j.fertnstert.2022.08.846. PMID: 36182261

The endometrial microbiome and its impact on human conception. Toson B, Simon C, Moreno I. International Journal of Molecular Sciences. 2022 Jan 1;23(1):485. doi: 10.3390/ijms23010485. PMID: 35008911

Bacterial Vaginosis and Its Association with Infertility, Endometritis, and Pelvic Inflammatory Disease. Ravel J, Moreno Gimeno I, Simon Valles C. American Journal of Obstetrics and Gynecology. 2021 Mar;224(3):251-257. doi: 10.1016/j.ajog.2020.10.019. PMID: 33091407

Clinical validity and utility of preconception expanded carrier screening for the management of reproductive genetic risk in IVF and general population. Capalbo A, Fabiani M, Caroselli S, Poli M, Girardi L, Patassini C, Favero F, Cimadomo D, Vaiarelli A, Simon C, Rienzi LF, Ubaldi FM. Human Reproduction. 2021 Jun 18;36(7):2050-2061. doi: 10.1093/humrep/deab087. PMID: 34021342

Consensus vision. Simon C. Fertility and Sterility. 2021 Jul;116(1):13-14. doi: 10.1016/j.fertnstert.2021.05.090. PMID: 34148581

Disrupted PGR-B and ESR1 signaling underlies defective decidualization linked to severe preeclampsia. Garrido-Gomez T, Castillo-Marco N, Clemente-Ciscar M, Cordero T, Munoz-Blat I, Amadoz A, Jimenez-Almazan J, Monfort-Ortiz R, Climent R, Perales-Marin A, Simon C. eLife. 2021 Oct 28;10:e70753. doi: 10.7554/eLife.70753. PMID: 34709177

Embryo Genetics. Rubio C, Simon C. Genes. 2021 Jan 19;12(1):118. doi: 10.3390/genes12010118. PMID: 33477974

Endometrial factor in unexplained infertility and recurrent implantation failure. Santamaria X, Simon C. Seminars in Reproductive Medicine. 2021 Nov;39(5-06):227-232. doi: 10.1055/s-0041-1735199. PMID: 34425598

Invitro fertilization and andrology laboratories in 2030. Simon C, Campbell A, Gardner DK, Meseguer M, Miller KA, Montag M, Palermo GD, Cheung S, Keating D, Xie P, Rosenwaks Z, Rienzi L, Innocenti F, Cimadomo D, Ubaldi FM, Sakkas D, Tucker MJ, Nel-Themaat L. Fertility and Sterility. 2021 Jul;116(1):2-3. doi: 10.1016/j.fertnstert.2021.05.089. PMID: 34148585

Invitro fertilization and andrology laboratory in 2030: expert visions. Campbell A, Gardner DK, Meseguer M, Miller KA, Montag M, Palermo GD, Cheung S, Keating D, Xie P, Rosenwaks Z, Rienzi L, Innocenti F, Cimadomo D, Ubaldi FM, Sakkas D, Tucker MJ, Nel-Themaat L, Simon C. Fertility and Sterility. 2021 Jul;116(1):4-12. doi: 10.1016/j.fertnstert.2021.05.088. PMID: 34148588

Molecular and cellular insights into the development of uterine fibroids. Machado-Lopez A, Simon C, Mas A. International Journal of Molecular Sciences. 2021 Aug 6;22(16):8483. doi: 10.3390/ijms22168483. PMID: 34445194

Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial. Capalbo A, Poli M, Rienzi L, Girardi L, Patassini C, Fabiani M, Cimadomo D, Benini F, Farcomeni A, Cuzzi J, Rubio C, Albani E, Sacchi L, Vaiarelli A, Figliuzzi M, Findikli N, Coban O, Boynukalin FK, Vogel I, Hoffmann E, Livi C, Levi-Setti PE, Ubaldi FM, Simon C. American Journal of Human Genetics. 2021 Dec 2;108(12):2238-2247. doi: 10.1016/j.ajhg.2021.11.002. PMID: 34798051

Noninvasive preimplantation genetic testing for aneuploidy: is the glass half-empty or half-full?. Rubio C, Simon C. Fertility and Sterility. 2021 Jun;115(6):1426-1427. doi: 10.1016/j.fertnstert.2021.04.002. PMID: 34053511

Obesity affects endometrial receptivity by displacing the window of implantation. Bellver J, Marin C, Lathi RB, Murugappan G, Labarta E, Vidal C, Giles J, Cabanillas S, Marzal A, Galliano D, Ruiz-Alonso M, Simon C, Valbuena D. Reproductive Sciences. 2021 Nov;28(11):3171-3180. doi: 10.1007/s43032-021-00631-1. PMID: 34033112

Preconception genome medicine: current state and future perspectives to improve infertility diagnosis and reproductive and health outcomes based on individual genomic data. Capalbo A, Poli M, Riera-Escamilla A, Shukla V, Kudo Hoffding M, Krausz C, Hoffmann E, Simon Valles C. Human Reproduction Update. 2021 Feb 19;27(2):254-279. doi: 10.1093/humupd/dmaa044. PMID: 33197264

Response to: Comments on the methodology of an endometrial receptivity array trial. Simon C, Gomez C, Ruiz M, Mol B, Valbuena D. Reproductive Biomedicine Online. 2021 Jan;42(1):284. doi: 10.1016/j.rbmo.2020.09.028. PMID: 33060012

Should vanishing twin pregnancies be systematically excluded from cell-free fetal DNA testing?. Balaguer N, Mateu Brull E, Serra V, Simon C, Milan M. Prenatal Diagnosis. 2021 Sep;41(10):1241-1248. doi: 10.1002/pd.5817. PMID: 32835421

Single-cell RNA Sequencing of SARS-CoV-2 cell entry factors in the preconceptional human endometrium. Vilella F, Wang W, Moreno I, Roson B, Quake S, Simon C. Human Reproduction. 2021 Sep 18;36(10):2709-2719. doi: 10.1093/humrep/deab183. PMID: 34329437

Sperm DNA methylation epimutation biomarker for paternal offspring autism susceptibility. Garrido N, Cruz F, Egea R, Simon C, Sadler-Riggleman I, Beck D, Nilsson E, Ben Maamar M, Skinner M. Clinical Epigenetics. 2021 Jan 7;13(1):6. doi: 10.1186/s13148-020-00995-2. PMID: 33413568

Understanding the human endometrium in the 21st century. Vilella F, Wang W, Moreno I, Quake SR, Simon C. American Journal of Obstetrics and Gynecology. 2021 Jul;225(1):1-2. doi: 10.1016/j.ajog.2021.04.224. PMID: 34023092

Projects
Reference: 874867 – HUTER
Title: Human Uterus Cell Atlas
Funding body: European Commission
Principal Investigator: Carlos Simón Vallés
Duration: 2020 – 2022
Total budget: 4.118.943 €
Reference: RTI2018-094946-B-I00
Title: Contribución materna en la patogénesis de enfermedades gestacionales tardías como la preeclampsia
Funding body: Ministerio de Ciencia, Innovación y Universidades
Principal Investigator: Carlos Simón Vallés
Duration: 2019 – 2022
Total budget: 254.100 €
Reference: PROMETEO/2018/161
Title: Medicina regenerativa del útero humano: desde la terapia celular a la creación del órgano mediante bioingeniería
Funding body: Conselleria de Educación, Cultura y Deporte
Principal Investigator: Carlos Simón Vallés
Duration: 2018 – 2021
Total budget: 297.066 €
Reference: BFU 2015-72131-EXP
Title: Criptocromos, la inexplicable presencia de sensores de luz en la oscuridad que conectan el embrión temprano con el cosmos
Funding body: Ministerio de Economía y Competitividad
Principal Investigator: Carlos Simón Vallés
Duration: 2017 – 2019
Total budget: 60.000 €
+ Info
Title: Molecular investigation on the etiology of preeclampsia and new strategies for its early diagnosis
Doctoral candidate: Castillo Marco, Nerea
Director(s): Simón Vallés, Carlos; Garrigo Gómez Tamara
Date of the defense: 20/06/2023
University: University de Valencia

Title: Analysis of the endometrial microbiome and its impact on human reproduction
Doctoral candidate: García Grau, Iolanda
Director(s): Simón Vallés, Carlos; Moreno Gimeno, Inmaculada; Remohí Giménez, Jose
Date of the defense: 11/06/2021
University: Universitat de València

Title: Decidualización defectuosa durante y después de un embarazo con preeclampsia revela la contribución materna en la etiología de la enfermedad
Doctoral candidate: Rubert Torró, Laura
Director(s): Perales Marín, Alfredo; Simón Vallés, Carlos; Garrido Gómez, Tamara
Date of the defense: 08/02/2021
University: Universitat de València

Title: Extracellular vesicles in the human maternal-embryo crosstalk during the preconception period
Doctoral candidate: Bolumar Recuero, David
Director(s): Simón Vallés, Carlos; Vilella Mitjana, Felipe
Date of the defense: 21/12/2020
University: Universitat de València

Title: Epigenetic analysis of cell-free dna as a tool to study pathogenesis and maternal syndrome of preeclampsia
Doctoral candidate: Corachán García, Irene
Director(s): Simón Vallés, Carlos; Díez Juan, Antonio; Vilella Mitjana, Felipe
Date of the defense: 14/02/2020
University: Universitat de València

Title: Maternal-fetal crosstalk. Elucitaing the role of mir30d in endometrial receptivity and pregnancy outcome
Doctoral candidate: Balaguer Cuenca, Nuria
Director(s): Vilella Mitjana, Felipe; Simón Vallés, Carlos
Date of the defense: 14/01/2019
University: Universitat de València