MALDI-IMS combined with shotgun proteomics identify and localize new factors in male infertility.

• Spermatogenesis is a complex multi-step process involving intricate interactions between different cell types in the male testis. Disruption of these interactions results in infertility. Combination of shotgun tissue proteomics with MALDI imaging mass spectrometry is markedly potent in revealing topological maps of molecular processes within tissues. Here, we use a combinatorial approach on a characterized mouse model of hormone induced male infertility to uncover misregulated pathways. Comparative testicular proteome of wild-type and mice overexpressing human P450 aromatase (AROM+) with pathologically increased estrogen levels unravels gross dysregulation of spermatogenesis and emergence of pro-inflammatory pathways in AROM+ testis. In situ MS allowed us to localize misregulated proteins/peptides to defined regions within the testis. Results suggest that infertility is associated with substantial loss of proteomic heterogeneity, which define distinct stages of seminiferous tubuli in healthy animals. Importantly, considerable loss of mitochondrial factors, proteins associated with late stages of spermatogenesis and steroidogenic factors characterize AROM+ mice. Thus, the novel proteomic approach pinpoints in unprecedented ways the disruption of normal processes in testis and provides a signature for male infertility.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Animals

Aromatase

genetics

metabolism

Disease Models

Animal

Estrogens

analysis

metabolism

Humans

Infertility

Male

genetics

metabolism

Male

Mice

Mice

Transgenic

Protein Interaction Maps

Proteome

analysis

Proteomics

methods

Spectrometry

Mass

Matrix-Assisted Laser Desorption-Ionization

methods

Spermatogenesis

genetics

Testis

chemistry

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)