Study of expression of genes potentially responsible for reduced fitness in patients with myotonic dystrophy type 1 and identification of new biomarkers of testicular function.
Adolescent
Adult
Anti-Mullerian Hormone
/ blood
Azoospermia
/ diagnosis
Biomarkers
/ blood
Fertility
/ genetics
Gene Expression
Homeodomain Proteins
/ blood
Humans
Male
Middle Aged
Myotonic Dystrophy
/ blood
Myotonin-Protein Kinase
/ blood
Proteins
/ analysis
Reverse Transcriptase Polymerase Chain Reaction
Semen
/ chemistry
Spermatozoa
/ pathology
Trinucleotide Repeat Expansion
/ genetics
Young Adult
RSPH6A
SIX5
anti-Müllerian hormone
gonadal function
myotonic dystrophy type 1
Journal
Molecular reproduction and development
ISSN: 1098-2795
Titre abrégé: Mol Reprod Dev
Pays: United States
ID NLM: 8903333
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
11
09
2019
accepted:
27
11
2019
pubmed:
17
12
2019
medline:
9
2
2021
entrez:
17
12
2019
Statut:
ppublish
Résumé
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by trinucleotide CTG expansion in DMPK gene, often affecting the neighboring genes. Endocrine system is involved, resulting in hypogonadism and reproductive abnormalities, but molecular mechanisms underlying the reduced fertility observed in DM1 are very complex and partially unknown. To better characterize these mechanisms, an analysis of sperm parameters and anti-Müllerian hormone (AMH) values was performed in 20 DM1 patients. About 50% of them showed hypoposia and azoospermia; the remaining, despite an adequate volume of ejaculate, had oligo-astheno-teratozoospermia. Interestingly, the lowest AMH levels better correlated with the main sperm alterations. The pattern of expression of DMPK, SIX5, and RSPH6A genes, evaluated by quantitative reverse transcription polymerase chain reaction, showed a substantial reduction of the expression in both peripheral blood and in seminal plasma of patients, compared to controls. An impairment of testis-specific RSPH6A protein expression and localization was observed in sperm protein extracts by WB analysis and in isolated spermatozoa by immunofluorescence. These results support the hypothesis that CTG expansion also affects the expression of neighboring genes and contributes to gonad defects observed in DM1, suggesting the possibility of using them as markers for normal fertility in humans.
Substances chimiques
Biomarkers
0
DMPK protein, human
0
Homeodomain Proteins
0
Proteins
0
RSPH6A protein, human
0
SIX5 protein, human
0
Anti-Mullerian Hormone
80497-65-0
Myotonin-Protein Kinase
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
45-52Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
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