MiR-17-5p/FOXL2/CDKN1B signal programming in oocytes mediates transgenerational inheritance of diminished ovarian reserve in female offspring rats induced by prenatal dexamethasone exposure
Prenatal dexamethasone exposure (PDE) induces long-term reproductive toxicity in female offspring. We sought to explore the transgenerational inheritance effects of PDE on diminished ovarian reserve (DOR) in female offspring. Dexamethasone was subcutaneously administered into pregnant Wistar rats fr...
Gespeichert in:
Veröffentlicht in: | Cell biology and toxicology 2023-06, Vol.39 (3), p.867-883 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Prenatal dexamethasone exposure (PDE) induces long-term reproductive toxicity in female offspring. We sought to explore the transgenerational inheritance effects of PDE on diminished ovarian reserve (DOR) in female offspring. Dexamethasone was subcutaneously administered into pregnant Wistar rats from gestational day 9 (GD9) to GD20 to obtain fetal and adult offspring of the F1 generation. F1 adult females were mated with normal males to produce the F2 generation, and the F3 generation. The findings showed decrease of serum levels of anti-Müllerian hormone (AMH) that in the PDE group, decrease in number of primordial follicles, and upregulation of
miR-17-5p
expression before birth in F1 offspring rats. Expression of cyclin-dependent kinase inhibitor 1B (CDKN1B) and Forkhead Box L2 (FOXL2) were downregulated, and binding of FOXL2 and the CDKN1B promoter region was decreased in PDE groups of the F1, F2, and F3 generations. In vitro intervention experiments showed that glucocorticoid receptor (GR) was involved in activity of dexamethasone. These findings indicate that PDE can activate GR in fetal rat ovary and induce DOR of offspring, and its heritability is mediated by the cascade effect of
miR-17-5p
/FOXL2/CDKN1B. Increase in
miR-17-5p
expression in oocytes is the potential molecular basis for transgenerational inheritance of PDE effects.
Graphical abstract |
---|---|
ISSN: | 0742-2091 1573-6822 |
DOI: | 10.1007/s10565-021-09645-6 |