title: Proteomic profile of maternal-aged blastocoel fluid suggests a novel role for ubiquitin system in blastocyst quality.
abstract: OBJECTIVE
  The etiology of maternal aging, a common cause of female factor infertility and a rate-limiting step in vitro fertilization (IVF) success, remains still unclear. Proteomic changes responsible for the impaired successful pregnancy outcome after IVF with aged blastocysts have not been yet evaluated. The objective of this prospective study was to employ proteomic techniques and bioinformatic tools to enlight differences at the protein level in blastocoel fluid of aged and younger woman.
  
  
  METHODS
  Protein composition of human blastocoel fluid isolated by micromanipulation from 46 blastocysts of women aged <37 years (group A) and 29 of women aged ≥37 years (group B) have been identified by a shotgun proteomic approach based on high-resolution nano-liquid chromatography electrospray-ionization-tandem mass spectrometry (nLC-ESI-MS/MS) using label free for the relative quantification of their expression levels.
  
  
  RESULTS
  The proteomic analysis leads to the identification and quantification of 148 proteins; 132 and 116 proteins were identified in groups A and B, respectively. Interestingly, the identified proteins are mainly involved in processes aimed at fine tuning embryo implantation and development. Among the 100 proteins commonly expressed in both groups, 17 proteins are upregulated and 44 downregulated in group B compared to group A. Overall, the analysis identified 33 proteins, which were increased or present only in B while 76 were decreased in B or present only in A.
  
  
  CONCLUSIONS
  Data revealed that maternal aging mainly affects blastocyst survival and implantation through unbalancing the equilibrium of the ubiquitin system known to play a crucial role in fine-tuning several aspects required to ensure successful pregnancy outcome.
authors.affiliation: Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Milan, Italy.|Fondazione Filarete, 20139, Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Tedeschi
authors.affiliation: Humanitas Fertility Center, Department of Gynecology, Division of Gynecology and Reproductive Medicine, Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Albani
authors.affiliation: Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milan, Italy. elena.borroni@humanitasresearch.it.
authors.forename: Elena Monica
authors.initials: EM
authors.lastname: Borroni
authors.affiliation: Humanitas Fertility Center, Department of Gynecology, Division of Gynecology and Reproductive Medicine, Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Parini
authors.affiliation: Humanitas Fertility Center, Department of Gynecology, Division of Gynecology and Reproductive Medicine, Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Brucculeri
authors.affiliation: Fondazione Filarete, 20139, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Maffioli
authors.affiliation: Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Milan, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Negri
authors.affiliation: Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Nonnis
authors.affiliation: Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.affiliation: Humanitas Fertility Center, Department of Gynecology, Division of Gynecology and Reproductive Medicine, Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
authors.forename: Paolo Emanuele
authors.initials: PE
authors.lastname: Levi-Setti
mesh_terms: D000328:Adult; D000367:Age Factors; D001755:Blastocyst / Q000502:physiology; D002470:Cell Survival; D010064:Embryo Implantation / Q000502:physiology; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008423:Maternal Age; D011247:Pregnancy; D011256:Pregnancy Outcome; D014176:Protein Biosynthesis / Q000235:genetics*; D040901:Proteomics; D053719:Tandem Mass Spectrometry
keywords: Aging; Blastocoel fluid; Embryo implantation; Proteomics; Shotgun