CURRENTLY, IT IS KNOWN THAT THE ORIGIN OF THE DEVELOPMENT OF SOME ADULT DISEASES IS RELATED TO INTRAUTERINE CONDITIONS DURING EMBRYONAL AND FOETAL DEVELOPMENT. PREGNANCY BEGINS WITH EMBRYONIC IMPLANTATION, HOWEVER, THE IMPACT IT HAS ON ADULT LIFE CONTINUES TO BE AN INCOGNITE. OUR RESEARCH GROUP HAS SHOWN THAT THE HUMAN ENDOMETRIAL EPITHELIUM IS ABLE TO SECRETE A SPECIFIC MIRNA PROFILE DURING THE TIME THE EMBRYO PENETRATES THE UTERINE CAVITY AND BEGINS ITS ADHESION TO THE UTERINE WALL. THE MATERNAL MIRNAS ARE SECRETED INTO THE ENDOMETRIAL FLUID, TRANSPORTED THROUGH EXOSOMES OR BOUND TO PROTEINS AND PENETRATE THE TROPHOECTODERM OF THE PREIMPLANTATION EMBRYO. THIS ENTRY OF MATERNAL MIRNAS IN THE EMBRYO INDUCES TRANSCRIPTOMICAS MODIFICATIONS THAT CAUSE CHANGES OF GREAT RELEVANCE AT BOTH MOLECULAR AND FUNCTIONAL LEVEL. OUR PUBLISHED DATA THEREFORE DEMONSTRATES A NEW PARADIGM: The MATERNAL REGULATION of the transcriptome of pre-implantation in physical situations._x000D_ OUR OUR OUR OUR OUR OUR OUR OUR OUR PROJECT IS TO USE THIS NEW MECANISM OF MATERNO-EMBRIONARY COMMUNICATION, with the end of buying and preventing the development of complex diseases that can be separated by pathological maternal conditions leading to EMBRIONARY IMPLANTATION, PREVIAS INCLUDED to EMBRIONARY IMPLEMENTATION. FOR THIS, WE HAVE TAKEN AS A MODEL INTRICATE METABOLIC ALTERATIONS SUCH AS MATERNAL OBESITY OR THOSE DISEASES INDUCED IN THE ADULT BY THE MOTHER’S EXPOSURE TO TOBACCO. THE FIRST OBJECTIVE OF THIS PROJECT IS TO IDENTIFY DIFFERENTIAL EXPRESSION PROFILES OF MIRNAS SECRETED TO ENDOMETRIAL FLUID IN WOMEN WHO SUFFER FROM THESE PATHOLOGICAL CONDITIONS. IN OBESITY, COMPARING THIS PROFILE WITH NON-OBESE PATIENTS AND CHECKING THAT THIS PROFILE IS NORMALISED WHEN OBESE PATIENTS LOSE WEIGHT. IN PARALLEL, WE WILL USE A MURINE MODEL OF INDUCED OBESITY TO VALIDATE THIS HYPOTHESIS. WE WILL ALSO IDENTIFY THE EXPRESSION PROFILE OF MIRNAS SECRETED BY THE ENDOMETRIUM OF FUTURE MOTHERS SMOKING VS. NON-SMOKERS, AND WE WILL CHECK THEIR SPECIFICITY BY COMPARING THEM WITH THOSE OBTAINED IN THE SAME WOMEN ONE YEAR AFTER THEY HAVE QUIT SMOKING. AGAIN, WE WILL USE A MURINE SMOKING MODEL FOR ITS VALIDATION. THEN, THROUGH AN ANALYSIS IN SILICO, WILL WE IDENTIFY THE POSSIBLE REGULATED GENES AS WELL AS THE FUNCTIONAL PATHWAYS INVOLVED IN BOTH PATHOLOGICAL CONDITIONS, BOTH IN THE HUMAN AND MURINE MODEL. THEN WE WILL PROCEED TO IDENTIFY THE TRANSCRIPTOMICAS AND EPIGENETIC MODIFICATIONS INDUCED BY THE MATERNAL MIRNAS OF OBESE OR SMOKING WOMEN IN PREIMPLANTATION MURINE EMBRYOS. FINALLY, WE WILL USE THE ANIMAL MODELS DESCRIBED FOR BOTH PATHOLOGIES TO DEMONSTRATE IN THE BREEDS THE IMPACT OF MATERNAL REGULATION ON THE DEVELOPMENT OF PATHOLOGIES OF ADULTS. AS PRELIMINARY RESULTS THAT SUPPORT THIS PROJECT, WE PRESENT OUR MODEL OF MATERNAL REGULATION OF THE TRANSCRIPTOME OF THE PREIMPLANTATION EMBRYO IN PHYSIOLOGICAL CONDITIONS AND THE PRELIMINARY IDENTIFICATION OF THE DIFFERENTIAL PROFILE OF MIRNAS SECRETED TO THE ENDOMETRIAL FLUID IN OBESE WOMEN. IT IS PROPOSED TO IMPLEMENT THIS NEW MATERNAL MECHANISM TO UNDERSTAND AND PREVENT THE PRE-IMPLANTATION OF ADULT DISEASES ASSOCIATED WITH OBESITY AND TOBACCO EXPOSURE.
