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Loss of the glucocorticoid receptor causes accelerated reproductive aging in female zebrafish


Faught, Erin; Santos, Helio; Vijayan, Mathilakath (2020), Loss of the glucocorticoid receptor causes accelerated reproductive aging in female zebrafish, Dryad, Dataset,


Reproductive decline in mid-adult females isstablished phenotype of the aging process. Stress and the rise in glucocorticoids (GCs) accelerate reproductive aging, but little is known about the mechanisms involved. During stress, GCs activate the glucocorticoid receptor (GR), a ubiquitously expressed, ligand-bound transcription factor, to elicit physiological changes for restoring homeostasis. Here we tested the hypothesis that GC-GR signalling is essential for accelerating reproductive aging. To test this, we used a ubiquitous GR knockout (GRKO) zebrafish, which is inherently hypercortisolemic, to delineate the role of high cortisol and GR signalling on reproductive aging. The loss of GR led to premature reproductive aging, including high frequency of typical and atypical follicular atresia in vitellogenic oocytes, including yolk liquefaction and large inflammatory infiltrates. The reduction in oocyte quality was also associated with a decline in ovarian tert expression in the adult GRKO fish compared to the early-adult GRKO and adult wildtype zebrafish. Accelerated reproductive aging also impacted the progeny, including lower breeding success, fecundity, egg fertilization rate, and delayed somitogenesis and embryo survival in the adult GRKO fish. We adduce that GR signalling is essential for prolonging the reproductive life span and improving the egg quality and embryo viability in zebrafish.


Natural Sciences and Engineering Research Council of Canada

Fundação de Amparo à Pesquisa do Estado de Minas Gerais