Dehydroepiandrosterone supplementation attenuates ovarian ageing in a galactose-induced primary ovarian insufficiency ra
- PDF / 6,701,451 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 96 Downloads / 168 Views
REPRODUCTIVE PHYSIOLOGY AND DISEASE
Dehydroepiandrosterone supplementation attenuates ovarian ageing in a galactose-induced primary ovarian insufficiency rat model Berna Sozen 1,2 & Murat Ozekinci 3,4 & Munire Erman 3 & Tonguc Gunduz 5 & Necdet Demir 1 & Randa Akouri 6 Received: 24 January 2019 / Accepted: 7 August 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Purpose Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI). The unique pathophysiology of classic galactosemia, with a severely reduced follicle pool at an early age, requires a new therapeutic approach. This study evaluated the effect of dehydroepiandrosterone (DHEA) on ovarian tissue in a galactose-induced POI rat model. Methods Pregnant rats were fed with either a normal or a 35% galactose-containing diet from day 3 of conception continuing through weaning of the litters. Galactose-exposed female offspring were further divided into 5 groups on PND21. The first group received no application. Treatment groups were fed orally by gavage once daily with sesame oil (group 2), or DHEA at doses of 0.1 mg/kg (group 3), 1 mg/kg (group 4) or 10 mg/kg (group 5) until PND70. Fertility rates of mothers with galactosemia, body weights (BWs), and ovarian weights of the litters from PND21 to PND70 were recorded. Ovarian follicle count, immunohistochemistry for proliferation and apoptosis marker expressions and TUNEL for cell death assessment were performed in offspring ovaries. Results Decreased fertility, ovarian/body weights were observed under galactosemic conditions, together with decreased follicle number and increased atresia. Improved postnatal development, primordial follicle recruitment and follicular growth were observed after DHEA treatment. After DHEA treatment, the expression of Ki67 protein was found to be increased; elevated expression of cleaved-caspase-3 under galactosemia was found to be reduced. Conclusions Our data suggests that DHEA treatment may be a potentially useful clinical therapy to improve ovarian ageing in women with POI-induced by galactosemia. Keywords Rat . Galactosemia . Primary ovarian insufficiency . DHEA
Berna Sozen and Murat Ozekinci contributed equally to this work. * Murat Ozekinci [email protected] 1
Department of Histology and Embryology, School of Medicine, Akdeniz University, Campus, 07070 Antalya, Turkey
2
Present address: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
3
Department of Obstetrics and Gynecology, Akdeniz University School of Medicine, 07058 Antalya, Turkey
4
IVF Andrologia and Genetics Center, Antalya Memorial Hospital, Yildirim Beyazit St. Kepez, 07025 Antalya, Turkey
5
Department of Obstetrics and Gynecology, Memorial Private Hospital, Antalya, Turkey
6
Department of Obstetrics and Gynecology, Goteburg University, Gothenburg, Sweden
Introduction Premature activation of ovarian follicles leads to early depletion of the ovarian reserve, known
Data Loading...
