in utero exposure to metformin reduces the ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
in utero exposure to metformin reduces the fertility of male offspring in adulthood
Author(s) :
Faure, Melanie C. [Auteur]
Khoueiry, Rita [Auteur]
Quanico, Jusal [Auteur]
Acloque, Herve [Auteur]
Guerquin, Marie-Justine [Auteur]
Bertoldo, Michael J. [Auteur]
Chevaleyre, Claire [Auteur]
Rame, Christelle [Auteur]
FOURNIER, Isabelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Dupont, Joelle [Auteur]
Froment, Pascal [Auteur]
Khoueiry, Rita [Auteur]
Quanico, Jusal [Auteur]
Acloque, Herve [Auteur]
Guerquin, Marie-Justine [Auteur]
Bertoldo, Michael J. [Auteur]
Chevaleyre, Claire [Auteur]
Rame, Christelle [Auteur]
FOURNIER, Isabelle [Auteur]

Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]

Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Dupont, Joelle [Auteur]
Froment, Pascal [Auteur]
Journal title :
Frontiers in Endocrinology
Abbreviated title :
Front Endocrinol (Lausanne)
Volume number :
12
Pages :
750145
Publisher :
Frontiers
Publication date :
2021-10-18
ISSN :
1664-2392
English keyword(s) :
pregnancy
metformin
spermatozoa
testis
ovary
embryo
metformin
spermatozoa
testis
ovary
embryo
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Metformin is a drug used for the treatment of type 2 diabetes and disorders associated with insulin resistance. Metformin is also used in the treatment of pregnancy disorders such as gestational diabetes. However, the ...
Show more >Metformin is a drug used for the treatment of type 2 diabetes and disorders associated with insulin resistance. Metformin is also used in the treatment of pregnancy disorders such as gestational diabetes. However, the consequences of foetal exposure to metformin on the fertility of exposed offspring remain poorly documented. In this study, we investigated the effect of in utero metformin exposure on the fertility of female and male offspring. We observed that metformin is detectable in the blood of the mother and in amniotic fluid and blood of the umbilical cord. Metformin was not measurable in any tissues of the embryo, including the gonads. The effect of metformin exposure on offspring was sex specific. The adult females that had been exposed to metformin in utero presented no clear reduction in fertility. However, the adult males that had been exposed to metformin during foetal life exhibited a 30% reduction in litter size compared with controls. The lower fertility was not due to a change in sperm production or the motility of sperm. Rather, the phenotype was due to lower sperm head quality - significantly increased spermatozoa head abnormality with greater DNA damage - and hypermethylation of the genomic DNA in the spermatozoa associated with lower expression of the ten-eleven translocation methylcytosine dioxygenase 1 (TET1) protein. In conclusion, while foetal metformin exposure did not dramatically alter gonad development, these results suggest that metabolic modification by metformin during the foetal period could change the expression of epigenetic regulators such as Tet1 and perturb the genomic DNA in germ cells, changes that might contribute to a reduced fertility.Show less >
Show more >Metformin is a drug used for the treatment of type 2 diabetes and disorders associated with insulin resistance. Metformin is also used in the treatment of pregnancy disorders such as gestational diabetes. However, the consequences of foetal exposure to metformin on the fertility of exposed offspring remain poorly documented. In this study, we investigated the effect of in utero metformin exposure on the fertility of female and male offspring. We observed that metformin is detectable in the blood of the mother and in amniotic fluid and blood of the umbilical cord. Metformin was not measurable in any tissues of the embryo, including the gonads. The effect of metformin exposure on offspring was sex specific. The adult females that had been exposed to metformin in utero presented no clear reduction in fertility. However, the adult males that had been exposed to metformin during foetal life exhibited a 30% reduction in litter size compared with controls. The lower fertility was not due to a change in sperm production or the motility of sperm. Rather, the phenotype was due to lower sperm head quality - significantly increased spermatozoa head abnormality with greater DNA damage - and hypermethylation of the genomic DNA in the spermatozoa associated with lower expression of the ten-eleven translocation methylcytosine dioxygenase 1 (TET1) protein. In conclusion, while foetal metformin exposure did not dramatically alter gonad development, these results suggest that metabolic modification by metformin during the foetal period could change the expression of epigenetic regulators such as Tet1 and perturb the genomic DNA in germ cells, changes that might contribute to a reduced fertility.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
INSERM
Université de Lille
Université de Lille
Submission date :
2022-06-15T14:00:32Z
2023-03-09T13:32:13Z
2023-03-09T13:32:13Z
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