Proteome-wide and matrisome-specific atlas of the human ovary from prepuberty to menopause

ABSTRACT: Our modern era is witnessing an increasing infertility rate worldwide. Although some of the causes can be attributed to our modern lifestyle (eg. persistent organic polluants, late pregnancy), our knowledge of the human ovarian tissue has remained limited and insufficient to reverse the infertility statistics. Indeed, all efforts have been focused on the endocrine and cellular function in support of the cell theory that dates back to the 18th century, while the human ovarian matrisome is still under-described. Therefore, hereby we provide the first systematic study focusing on the human ovarian matrisome and its remodeling during a woman lifetime, from prepuberty til menopause. We apply our matrisome tailored fractionation method, the DC-MaP strategy and mass spectrometry-based quantitative proteomics using TMT pro 16-plex isobaric labeling to delineate proteome-wide and ECM-specific shifts between prepubertal, reproductive-age and menopausal stages. Post-translational modifications, namely proline hydroxylation and advanced glycation ends products have also been detected at different intensities according to age. Matrisome age-biomarkers have been validated with lightsheet microscopy-based-3D imaging, following immunofluorescence and tissue clearing with an ovary-tailored protocol. We used machine learning and statistics to build a neural network that can predict predict the probability of a specific ovarian tissue matrisome to resemble to prepubertal, reproductive-age or menopausal tissue and potentially conclude its fertility potency or evaluate in the future the efficiency of ovarian rejuvenation treatments. We also used NLP medscan technology for advanced literature text-mining to predict all possible-connections between the extra- and intra-cellular compartments and how chemo-radiotherapy, known for its gonadotoxicity can also affect key matrisome proteins.This comprehensive proteomics analysis represents the ovarian proteomic codex and contributes to an improved understanding of the critical roles that ECM plays throughout ovarian life span. By publishing our proteomic data, we hope to open new avenues in fertility restoration, ovarian rejuvenation and reproductive tissue engineering

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Ovary

SUBMITTER: Didier Vertommen  

LAB HEAD: Christiani Andrade Amorim

PROVIDER: PXD025940 | Pride | 2022-04-06

REPOSITORIES: Pride