PMID- 32727081
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20231112
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 8
DP  - 2020 Jul 27
TI  - Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated 
      Destruction Cascade during Epididymal Sperm Maturation in Mice.
LID - 10.3390/cells9081789 [doi]
LID - 1789
AB  - Protamines are the safeguards of the paternal sperm genome. They replace most of 
      the histones during spermiogenesis, resulting in DNA hypercondensation, thereby 
      protecting its genome from environmental noxa. Impaired protamination has been 
      linked to male infertility in mice and humans in many studies. Apart from 
      impaired DNA integrity, protamine-deficient human and murine sperm show multiple 
      secondary effects, including decreased motility and aberrant head morphology. In 
      this study, we use a Protamine-2 (Prm2)-deficient mouse model in combination with 
      label-free quantitative proteomics to decipher the underlying molecular processes 
      of these effects. We show that loss of the sperm's antioxidant capacity, 
      indicated by downregulation of key proteins like Superoxide dismutase type 1 
      (SOD1) and Peroxiredoxin 5 (PRDX5), ultimately initiates an oxidative 
      stress-mediated destruction cascade during epididymal sperm maturation. This is 
      confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for 
      oxidative stress-mediated DNA damage. Prm2-deficient testicular sperm are not 
      affected and initiate the proper development of blastocyst stage preimplantation 
      embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our 
      results provide new insight into the role of Prm2 and its downstream molecular 
      effects on sperm function and present an important contribution to the 
      investigation of new treatment regimens for infertile men with impaired 
      protamination.
FAU - Schneider, Simon
AU  - Schneider S
AUID- ORCID: 0000-0001-9894-5608
AD  - Department of Developmental Pathology, Institute of Pathology, University 
      Hospital Bonn, 53127 Bonn, Germany.
FAU - Shakeri, Farhad
AU  - Shakeri F
AD  - Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, 
      University of Bonn, 53127 Bonn, Germany.
AD  - Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University 
      of Bonn, 53127 Bonn, Germany.
FAU - Trotschel, Christian
AU  - Trotschel C
AD  - Department of Plant Biochemistry, Ruhr-University Bochum, 44801 Bochum, Germany.
FAU - Arevalo, Lena
AU  - Arevalo L
AD  - Department of Developmental Pathology, Institute of Pathology, University 
      Hospital Bonn, 53127 Bonn, Germany.
FAU - Kruse, Alexander
AU  - Kruse A
AUID- ORCID: 0000-0001-5526-9347
AD  - Department of Urology, Pediatric Urology and Andrology, Section Molecular 
      Andrology, Biomedical Research Center of the Justus-Liebig University Giessen, 
      35392 Giessen, Germany.
FAU - Buness, Andreas
AU  - Buness A
AD  - Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, 
      University of Bonn, 53127 Bonn, Germany.
AD  - Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University 
      of Bonn, 53127 Bonn, Germany.
FAU - Poetsch, Ansgar
AU  - Poetsch A
AUID- ORCID: 0000-0002-7540-3475
AD  - Department of Plant Biochemistry, Ruhr-University Bochum, 44801 Bochum, Germany.
AD  - Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for 
      Marine Science and Technology, Qingdao 266237, China.
AD  - College of Marine Life Sciences, Ocean University of China, Qingdao 266003, 
      China.
FAU - Steger, Klaus
AU  - Steger K
AD  - Department of Urology, Pediatric Urology and Andrology, Section Molecular 
      Andrology, Biomedical Research Center of the Justus-Liebig University Giessen, 
      35392 Giessen, Germany.
FAU - Schorle, Hubert
AU  - Schorle H
AD  - Department of Developmental Pathology, Institute of Pathology, University 
      Hospital Bonn, 53127 Bonn, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200727
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Protamines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (protamine 2)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Humans
MH  - Infertility, Male/*physiopathology
MH  - Male
MH  - Mice
MH  - Protamines/*metabolism
MH  - Reactive Oxygen Species
MH  - Spermatogenesis/*physiology
MH  - Spermatozoa/*physiology
PMC - PMC7463811
OTO - NOTNLM
OT  - ROS
OT  - infertility
OT  - protamines
OT  - sperm
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/07/31 06:00
MHDA- 2021/04/01 06:00
PMCR- 2020/08/01
CRDT- 2020/07/31 06:00
PHST- 2020/06/29 00:00 [received]
PHST- 2020/07/16 00:00 [revised]
PHST- 2020/07/24 00:00 [accepted]
PHST- 2020/07/31 06:00 [entrez]
PHST- 2020/07/31 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - cells9081789 [pii]
AID - cells-09-01789 [pii]
AID - 10.3390/cells9081789 [doi]
PST - epublish
SO  - Cells. 2020 Jul 27;9(8):1789. doi: 10.3390/cells9081789.