A Draft Map of the Human Ovarian Proteome for Tissue Engineering and Clinical Applications

Abstract

Fertility preservation research in women today is increasingly taking advantage of bioengineering techniques to develop new biomimetic materials and solutions to safeguard ovarian cell function and microenvironment in vitro, and in vivo,. However, available data on the human ovary are limited and fundamental differences between animal models and humans are hampering researchers in their quest for more extensive knowledge of human ovarian physiology and key reproductive proteins that need to be preserved. We therefore turned to multi-dimensional label-free mass spectrometry to analyze human ovarian cortex, as it is a high-throughput and conclusive technique providing information on the proteomic composition of complex tissues like the ovary. In-depth proteomic profiling through two-dimensional liquid chromatography-mass spectrometry, Western blotting, histological and immunohistochemical analyses, and data mining helped us to confidently identify 1508 proteins. Moreover, our method allowed us to chart the most complete representation so far of the ovarian matrisome, defined as the ensemble of extracellular matrix proteins and associated factors, including more than 80 proteins. In conclusion, this study will provide a better understanding of ovarian proteomics, with a detailed characterization of the ovarian follicle microenvironment, in order to enable bioengineers to create biomimetic scaffolds for transplantation and three-dimensional in vitro, culture. By publishing our proteomic data, we also hope to contribute to accelerating biomedical research into ovarian health and disease in general.

Bone secreted factors induce cellular quiescence in prostate cancer cells

“…Next, we compared our list of bone-secreted proteins to the extracellular matrix (ECM) protein atlas compiled by the Matrisome Project (http://matrisomeproject.mit.edu) 15,16 . The ECM protein atlas contains an inventory of matrisomes identified from normal lung, liver and colon tissues as well as metastatic colon, melanoma, myeloma and mammary tissues 15–18 , ovary 19 , endothelial cells 20 , pancreatic islet cells 21 , and various stem-cell derived ECMs 22 . According to the classification of the matrisome proteome 15 , the 132 bone-secreted proteins can be grouped into three major categories: “Matrisome Core” proteins (63 proteins), “Matrisome-Associated” proteins (42 proteins), and “Other Secreted Factors” (27 proteins).…”

Proteomic analyses of decellularized porcine ovaries identified new matrisome proteins and spatial differences across and within ovarian compartments

“…There have been previous reports examining the ovarian proteome with one focusing on the ovarian matrisome 24,25 . However, this study focused solely on the human ovarian cortex and did not examine the composition of the medulla.…”

“…Previous studies examined the ovarian matrisome of human cortical tissue or whole ovaries 24,25 . However, none have examined the differences between the two main compartments or considered the three-dimensional composition of the ovarian matrisome.…”

The Human Ovary and Future of Fertility Assessment in the Post-Genome Era

“…On this basis, any synthetic process used can be monitored and improved, which also allows for the tracking of the composition of the neoformed ECM after transplantation. The team has already succeeded in establishing the most complete proteomic description of the human ovary to date, while at the same time revealing the composition of its ECM [22].…”