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

• Published in: Journal of assisted reproduction and genetics 2019-10, Vol.36 (10), p.2181-2189
• Main Authors: Sozen, Berna, Ozekinci, Murat, Erman, Munire, Gunduz, Tonguc, Demir, Necdet, Akouri, Randa
• Format: Article
• Language: English
• Subjects: Aging; Aging - drug effects; Aging - genetics; Animals; Apoptosis; Caspase; Caspase-3; Cell death; Dehydroepiandrosterone; Dehydroepiandrosterone - pharmacology; DHEA; Dietary Supplements; Disease Models, Animal; Female; Fertility; Galactose; Galactose - toxicity; Galactosemia; Galactosemias - chemically induced; Galactosemias - complications; Galactosemias - diet therapy; Galactosemias - pathology; Gynecology; Human Genetics; Humans; Immunohistochemistry; Medical Genetics; Medicine; Medicine & Public Health; Medicinsk genetik; Obstetrics, Gynecology and Reproductive Medicine; Offspring; Ovarian Follicle - drug effects; Ovarian Follicle - pathology; Ovaries; Pregnancy; Primary ovarian insufficiency; Primary Ovarian Insufficiency - chemically induced; Primary Ovarian Insufficiency - diet therapy; Primary Ovarian Insufficiency - pathology; Rat; Rats; Reproductive Medicine; Reproductive Physiology and Disease; Reproduktionsmedicin och gynekologi; Rodents; Weaning
• ISSN: 1058-0468; 1573-7330; 1573-7330
• DOI: 10.1007/s10815-019-01560-4

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.