Format

Send to

Choose Destination
Epigenomics. 2016 Nov;8(11):1459-1479. Epub 2016 Oct 20.

Developmental epigenetic programming of adult germ cell death disease: Polycomb protein EZH2-miR-101 pathway.

Author information

1
Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 5, Nice F-06204, France.
2
Université de Nice Sophia-Antipolis, Unité de Formation et de Recherche (UFR) Médecine, Nice F-06000, France.
3
Centre Hospitalier Universitaire de Nice, Pôle de Digestif-Obstétrique, Centre de Reproduction, Nice F-06202, France.
4
Centre Hospitalier Universitaire de Nice, Pôle de Biologie, Centre de Reproduction, Nice F-06202, France.
5
Centre Hospitalier Universitaire de Nice, Pôle d'Urologie, Service d'Urologie, Nice F-06202, France.
6
Institut National de la Santé et de la Recherche Médicale, Unité 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 10, Nice F-06204, France.
7
Centre Hospitalier Universitaire de Nice, Pôle de Biologie, Service d'Anatomie et de Cytologie Pathologiques, Nice F-06202, France.
8
Division of Paediatrics & DOHaD Laboratory, CHUV & University of Lausanne, CH-1011, Switzerland.
9
BASF Agro, Ecully F-69130, France.
10
Université Lyon 1, UFR Médecine Lyon Sud, Lyon F-69921, France.
11
Hospices Civils de Lyon, Hopital Lyon Sud, Laboratoire d'Anatomie et de Cytologie Pathologiques, Pierre-Bénite F-69495, France.
12
Centre Hospitalier Universitaire de Nice, Département de Recherche Clinique et d'Innovation, Nice F-06001, France.

Abstract

AIM:

The Developmental Origin of Health and Disease refers to the concept that early exposure to toxicants or nutritional imbalances during perinatal life induces changes that enhance the risk of developing noncommunicable diseases in adulthood. Patients/materials & methods: An experimental model with an adult chronic germ cell death phenotype resulting from exposure to a xenoestrogen was used.

RESULTS:

A reciprocal negative feedback loop involving decreased EZH2 protein level and increased miR-101 expression was identified. In vitro and in vivo knockdown of EZH2 induced an apoptotic process in germ cells through increased levels of apoptotic factors (BIM and BAD) and DNA repair alteration via topoisomerase 2B deregulation. The increased miR-101 levels were observed in the animal blood, meaning that miR-101 may be a part of a circulating mark of germ cell death.

CONCLUSION:

miR-101-EZH2 pathway deregulation could represent a novel pathophysiological epigenetic basis for adult germ cell disease with environmental and developmental origins.

KEYWORDS:

Polycomb proteins EZH2; endocrine-disrupting chemicals; epigenetic programming; male infertility; miRNAs; non-communicable diseases

PMID:
27762633
DOI:
10.2217/epi-2016-0061
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center