The current knowledge on radiosensitivity of ovarian follicle development stages

Adriaens, I.; Smitz, Johan; Jacquet, P.

doi:10.1093/humupd/dmn063

Cited by 112 publications

(89 citation statements)

References 110 publications

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“…1A). This is presumably due to the sensitivity of oocytes to whole body irradiation 42 , that can lead to ovarian failure and subsequent estrogen deficiency. A study conducted in non-irradiated OVX C57BL/6 mice identified an estradiol dosing regimen (10 µg/kg, formulated in ricinus oil/benzyl benzoate, injected 5 times/week s.c.) that conferred near-physiological estrogen replacement to the uterus and bone (Suppl.…”

Section: Resultsmentioning

confidence: 99%

Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining Cells

Streicher

Heyny

Andrukhova

et al. 2017

Sci Rep

161

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Estrogen is critical for skeletal homeostasis and regulates bone remodeling, in part, by modulating the expression of receptor activator of NF-κB ligand (RANKL), an essential cytokine for bone resorption by osteoclasts. RANKL can be produced by a variety of hematopoietic (e.g. T and B-cell) and mesenchymal (osteoblast lineage, chondrocyte) cell types. The cellular mechanisms by which estrogen acts on bone are still a matter of controversy. By using murine reconstitution models that allow for selective deletion of estrogen receptor-alpha (ERα) or selective inhibition of RANKL in hematopoietic vs. mesenchymal cells, in conjunction with in situ expression profiling in bone cells, we identified bone lining cells as important gatekeepers of estrogen-controlled bone resorption. Our data indicate that the increase in bone resorption observed in states of estrogen deficiency in mice is mainly caused by lack of ERα-mediated suppression of RANKL expression in bone lining cells.Estrogen is an important regulator of bone mass. The role of estrogen for bone homeostasis in humans is illustrated by the fact that estrogen deficiency is one of the major causes of postmenopausal osteoporosis 1 . Estrogen acts through two receptors, estrogen receptor-alpha (ERα) and -beta (ERβ), with ERα being more important for the regulation of bone metabolism 2 . Estrogen receptors are widely expressed in a variety of cells in bone and bone marrow. However, the actual target cell responsible for mediating the effects of estrogen on bone is still a matter of debate 3 . One of the most important downstream mediators of the action of estrogen on bone is the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) system. RANKL is an essential cytokine for osteoclast differentiation, activation, and survival 4, 5 . RANKL is produced by a variety of cells such as cells of the stromal cell lineage, activated T lymphocytes, but also B lymphocytes 5 . OPG is a soluble decoy receptor for RANKL which binds RANKL, and thereby inhibits osteoclastogenesis 6 . RANKL acts through the receptor RANK which is expressed in the cell membrane of osteoclasts and osteoclast precursor cells 7 . RANKL, RANK, and OPG are essential, non-redundant factors for osteoclast biology. Osteoclasts are entirely absent in RANK or RANKL deficient mice, leading to osteopetrosis, whereas OPG-deficient mice exhibit excessive bone resorption and severe osteoporosis 5,7,8 . RANKL exists in two biologically active forms, a membrane-bound form and a soluble form. Membrane-bound RANKL can be shed by matrix metalloproteinase 14 or by a disintegrin and metalloproteinase (ADAM) 10 9 resulting in soluble RANKL. In addition, soluble RANKL is produced by immune cells as a primary secreted form 5 . It is well established that sex steroids regulate the RANKL-OPG axis in osteoblast-like cells in vitro 10,11 . There is good evidence that OPG is regulated directly by sex hormones, whereas the sex steroid-mediated regulation of RANKL appears to be mainly indirect [10][11][12][13] . In vivo, o...

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Section: Resultsmentioning

confidence: 99%

Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining Cells

Streicher

Heyny

Andrukhova

et al. 2017

Sci Rep

161

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“…[34][35][36][37][38] This occurs through targeted impacts of radiation therapy (type, dose, frequency, field) and chemotherapy agents (type, dose, frequency) on key ovarian components including the germ cells, somatic cells, stroma, or vasculature. Surprisingly, evidence was found of primordial and/or early-activated primary follicles in all participant samples examined in the different treatment categories (Figs.…”

Section: Ovarian Tissue From Pediatric and Teen Otc Participants Contmentioning

confidence: 99%

Pediatric and Teen Ovarian Tissue Removed for Cryopreservation Contains Follicles Irrespective of Age, Disease Diagnosis, Treatment History, and Specimen Processing Methods

Duncan

Pavone

Gunn

et al. 2015

Journal of Adolescent and Young Adult Oncology

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“…The degree of ovarian impairment is related to the volume treated, total irradiation dose, fractionation schedule and age at time of treatment (Meirow and Nugent, 2001;Wallace et al, 2005). The radiation sensitivity of ovaries depend on several factors like the developing stage of cell, animal species involved, dose of irradiation, dose-rate used and on post irradiation time (Aurora et al, 2012, Adriaens et al, 2009. Quantitation of the follicles in the present experiment showed that they have varied radio sensitivity.…”

Section: Resultsmentioning

confidence: 60%

Quantitative variations in ovarian follicles of female Sprague Dawley rats after exposure to low dose gamma radiation

Singh¹,

Sharma

Goyal

2014

JANS

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Abstract:In the present experiment, an attempt was made to assess the genetic risk of low dose radiations in mammals. For this purpose female Sprague Dawley rats, 11-12 weeks old, were irradiated with whole body Co 60 gamma rays in three fractionated doses of 0.10 Gy (cumulative dose 0.30 Gy) given at an interval of one month at two different dose-rates (0.00368 Gy/min. and 0.0589 Gy/min.). Ovaries were studied for quantitative evaluation of follicles at 1, 4, 12, 28 and 52 weeks after last fractionated exposure. Quantitation revealed lower number of ovarian follicles in irradiated animals than in controls. The follicular number decreased with the advancement of time after last exposure (i.e. 2 months) and reached a peak level on 28 weeks. After that the recovery was evident but the number remained below 25% of total follicles even at 52 weeks autopsy interval, which indicated an irreversible damage in ovarian tissue. Primary follicles were found to be the most radiosensitive among the various types of follicles. The highest loss in these follicles was noted at 12 weeks after exposure with the high dose-rate, where only 10.61% of them were scored. Dose-rate exhibited an inverse relationship with the number of surviving follicles. At the higher dose-rate (0.0589 Gy / min.), depletion in the total follicular number was significantly higher than at the low dose-rate (0.00368 Gy/min.) used.

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The current knowledge on radiosensitivity of ovarian follicle development stages

Abstract: The fact that genetic effects were observed in irradiated animals suggests that these could also occur in humans. The probability of such events remains low compared with the 'spontaneous' risks of genetic effects.

Cited by 112 publications

References 110 publications

Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining Cells

Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining Cells

Pediatric and Teen Ovarian Tissue Removed for Cryopreservation Contains Follicles Irrespective of Age, Disease Diagnosis, Treatment History, and Specimen Processing Methods

Quantitative variations in ovarian follicles of female Sprague Dawley rats after exposure to low dose gamma radiation

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