Journal of Assisted Reproduction and Genetics

, Volume 34, Issue 2, pp 225–238 | Cite as

Proteomic profile of maternal-aged blastocoel fluid suggests a novel role for ubiquitin system in blastocyst quality

  • Gabriella Tedeschi
  • Elena Albani
  • Elena Monica BorroniEmail author
  • Valentina Parini
  • Anna Maria Brucculeri
  • Elisa Maffioli
  • Armando Negri
  • Simona Nonnis
  • Mauro Maccarrone
  • Paolo Emanuele Levi-Setti
Embryo Biology



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.


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.


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.


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.


Blastocoel fluid Aging Embryo implantation Proteomics Shotgun 



We thank Dr. Francesca Grassi Scalvini and Dr. Fabiana Santagata for their skillful technical assistance.

Authors’ roles

G.T., E.A., V.P., A.B., and P.E.L.S. designed the research. G.T., E.A., V.P., A.B., E.M., A.N., and S.N. performed the research. G.T., E.A., V.P., A.B., E.M.B., E.M., A.N., S.N., and M.M. analyzed the data. G.T., E.A., V.P., A.B., E.M.B., and M.M. wrote the paper.

Compliance with ethical standards


None declared.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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10815_2016_842_MOESM3_ESM.pdf (102 kb)
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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Gabriella Tedeschi
    • 1
    • 2
  • Elena Albani
    • 3
  • Elena Monica Borroni
    • 4
    Email author
  • Valentina Parini
    • 3
  • Anna Maria Brucculeri
    • 3
  • Elisa Maffioli
    • 2
  • Armando Negri
    • 1
  • Simona Nonnis
    • 1
  • Mauro Maccarrone
    • 5
  • Paolo Emanuele Levi-Setti
    • 3
  1. 1.Dipartimento di Medicina VeterinariaUniversità degli Studi di MilanoMilanItaly
  2. 2.Fondazione FilareteMilanItaly
  3. 3.Humanitas Fertility Center, Department of Gynecology, Division of Gynecology and Reproductive MedicineHumanitas Research HospitalMilanItaly
  4. 4.Dipartimento di Biotecnologie Mediche e Medicina TraslazionaleUniversità degli Studi di MilanoMilanItaly
  5. 5.Department of MedicineCampus Bio-Medico University of RomeRomeItaly

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