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Dehydroepiandrosterone supplementation attenuates ovarian ageing in a galactose-induced primary ovarian insufficiency rat model

Artikel i vetenskaplig tidskrift
Författare Berna Sozen
Murat Ozekinci
Munire Erman
Tonguc Gunduz
Necdet Demir
Randa Racho El-Akouri
Publicerad i Journal of Assisted Reproduction and Genetics
Volym 36
Sidor 2181-2189
ISSN 1058-0468
Publiceringsår 2019
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi
Sidor 2181-2189
Språk en
Länkar doi.org/10.1007/s10815-019-01560-4
Ämnesord DHEA, Galactosemia, Primary ovarian insufficiency, Rat
Ämneskategorier Medicinsk genetik, Reproduktionsmedicin och gynekologi

Sammanfattning

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. 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.

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