PMID- 31002754
OWN - NLM
STAT- MEDLINE
DCOM- 20200803
LR  - 20201101
IS  - 2047-2927 (Electronic)
IS  - 2047-2919 (Print)
IS  - 2047-2919 (Linking)
VI  - 7
IP  - 6
DP  - 2019 Nov
TI  - Semen quality is affected by HLA class I alleles together with sexually 
      transmitted diseases.
PG  - 867-877
LID - 10.1111/andr.12625 [doi]
AB  - BACKGROUND: The human leukocyte antigen (HLA) locus includes several genes with 
      key roles in antigen presentation and immune response, some of them inclusively 
      found to be associated with non-obstructive azoospermia. Still, HLA connections 
      to other infertility phenotypes such as semen hyperviscosity (SHV), 
      asthenozoospermia (AST), and oligozoospermia (OLI) have been often neglected. 
      OBJECTIVES: In this work, we aimed to evaluate the association of HLA class I and 
      II genes with SHV, AST, and OLI phenotypes while exploring a possible role in an 
      adaptive immune response to sexually transmitted diseases (STD). MATERIALS AND 
      METHODS: Whole-exome sequencing was performed in a Portuguese cohort of 71 
      infertility cases and 68 controls, followed by HLA typing using a specific 
      software-HLA*PRG:LA tool. Molecular screenings of seven STD were carried out in a 
      subset of 72 samples (30 cases and 42 controls). RESULTS: Statistical tests 
      uncovered three protective alleles: HLA-A*11:01, associated with all forms of 
      male infertility (p = 0.0006); HLA-DQB1*03:02 with SHV and OLI (P(SHV)( ) 
      = 0.0303, P(OLI)( ) = 0.0153); and HLA-A*29:02 with OLI (p = 0.0355), which was 
      found to interfere in sperm number together with HPV (p = 0.0313). Five risk 
      alleles were also identified: two linked with SHV (HLA-B*50:01, p = 0.0278; and 
      HLA-C*06:02, p = 0.0461), another one with both SHV and OLI (HLA-DQA1*05:01, 
      P(SHV)( ) = 0.0444 and P(OLI) =0.0265), and two with OLI (HLA-C*03:03, 
      p = 0.0480; and HLA-DQB1*03:01, p = 0.0499). Here, HLA-C*03:03 carriers tend to 
      be HPV infected. CONCLUSIONS: The application of HLA*PRG:LA tool to the study of 
      male infertility provided novel insights for an HLA correlation with semen 
      quality, namely among SHV and OLI phenotypes. The discovery of an HLA-A*29:02/HPV 
      crosstalk, together with former reports of HLA alleles conferring 
      resistance-susceptibility to diverse human pathogens, raises the hypothesis of a 
      mechanistic link between male infertility, HLA polymorphism, and host response to 
      STD.
CI  - (c) 2019 American Society of Andrology and European Academy of Andrology.
FAU - Marques, P I
AU  - Marques PI
AUID- ORCID: 0000-0001-6050-628X
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto (i3S), 
      Porto, Portugal.
AD  - Institute of Molecular Pathology and Immunology of the University of Porto 
      (Ipatimup), Porto, Portugal.
FAU - Goncalves, J C
AU  - Goncalves JC
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto (i3S), 
      Porto, Portugal.
AD  - Institute of Molecular Pathology and Immunology of the University of Porto 
      (Ipatimup), Porto, Portugal.
FAU - Monteiro, C
AU  - Monteiro C
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto (i3S), 
      Porto, Portugal.
AD  - Institute of Molecular Pathology and Immunology of the University of Porto 
      (Ipatimup), Porto, Portugal.
FAU - Cavadas, B
AU  - Cavadas B
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto (i3S), 
      Porto, Portugal.
AD  - Institute of Molecular Pathology and Immunology of the University of Porto 
      (Ipatimup), Porto, Portugal.
AD  - Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, 
      Portugal.
FAU - Nagirnaja, L
AU  - Nagirnaja L
AD  - Department of Genetics, Washington University School of Medicine, St. Louis, MO, 
      USA.
FAU - Barros, N
AU  - Barros N
AD  - Center for Reproductive Genetics Alberto Barros, Porto, Portugal.
FAU - Barros, A
AU  - Barros A
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto (i3S), 
      Porto, Portugal.
AD  - Center for Reproductive Genetics Alberto Barros, Porto, Portugal.
AD  - Genetics, Department of Pathology, Faculty of Medicine, University of Porto, 
      Porto, Portugal.
FAU - Carvalho, F
AU  - Carvalho F
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto (i3S), 
      Porto, Portugal.
AD  - Genetics, Department of Pathology, Faculty of Medicine, University of Porto, 
      Porto, Portugal.
FAU - Lopes, A M
AU  - Lopes AM
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto (i3S), 
      Porto, Portugal.
AD  - Institute of Molecular Pathology and Immunology of the University of Porto 
      (Ipatimup), Porto, Portugal.
FAU - Seixas, S
AU  - Seixas S
AD  - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto (i3S), 
      Porto, Portugal.
AD  - Institute of Molecular Pathology and Immunology of the University of Porto 
      (Ipatimup), Porto, Portugal.
LA  - eng
GR  - PTDC/BEX- GMG/0242/2012/Fundacao para a Ciencia e a Tecnologia/International
GR  - IF/01262/2014/Fundacao para a Ciencia e a Tecnologia/International
GR  - POCI-01-0145-FEDER-007274/European Regional Development Fund/International
GR  - R01HD07864/Eunice Kennedy Shriver National Institute of Child Health and Human 
      Development/International
GR  - SFRH/BPD/120777/2016/Fundacao para a Ciencia e a Tecnologia/International
GR  - NORTE-01-0145-FEDER-000029/European Regional Development Fund/International
GR  - R01 HD078641/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190419
PL  - England
TA  - Andrology
JT  - Andrology
JID - 101585129
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Adult
MH  - Asthenozoospermia/genetics
MH  - Azoospermia/genetics
MH  - Gene Dosage/genetics
MH  - Gene Expression Profiling
MH  - Genetic Predisposition to Disease/*genetics
MH  - HLA-A Antigens/genetics
MH  - HLA-B Antigens/genetics
MH  - HLA-C Antigens/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Male
MH  - Oligospermia/genetics
MH  - Semen Analysis
MH  - Sexually Transmitted Diseases/*immunology
MH  - Sperm Motility/*genetics
MH  - Transcriptome/genetics
PMC - PMC6768700
MID - NIHMS1018987
OTO - NOTNLM
OT  - HPV
OT  - HLA-A
OT  - association study
OT  - male infertility
OT  - oligozoospermia
OT  - semen hyperviscosity
EDAT- 2019/04/20 06:00
MHDA- 2020/08/04 06:00
PMCR- 2020/11/01
CRDT- 2019/04/20 06:00
PHST- 2018/12/17 00:00 [received]
PHST- 2019/02/28 00:00 [revised]
PHST- 2019/03/14 00:00 [accepted]
PHST- 2019/04/20 06:00 [pubmed]
PHST- 2020/08/04 06:00 [medline]
PHST- 2019/04/20 06:00 [entrez]
PHST- 2020/11/01 00:00 [pmc-release]
AID - 10.1111/andr.12625 [doi]
PST - ppublish
SO  - Andrology. 2019 Nov;7(6):867-877. doi: 10.1111/andr.12625. Epub 2019 Apr 19.