Galactose toxicity in the rat as a model for premature ovarian failure: an experimental approach readdressed.
BACKGROUND
The pathophysiological mechanisms underlying premature ovarian failure (POF) are largely unknown. Our objective was to develop a working animal model to explore the pathogenesis of POF. Since galactosaemic women eventually develop POF, we evaluated the potential of experimental galactose toxicity as the proposed model.


METHODS
Pregnant rats were fed pellets supplemented with or without 35% galactose from day 3 of conception continuing through weaning of the litters. Female offspring were evaluated for serum levels of galactose and galactose-1-phosphate, growth rate, onset of puberty, reproductive cyclicity, ovarian complement of follicles, hypothalamo-pituitary-ovarian function and follicular response to gonadotrophins.


RESULTS
Galactose toxicity delayed the onset of puberty and developed a state of hypergonadotrophic hypoestrogenism. The characteristic low FSH levels at weaning followed by pubertal spurts of gonadotrophins and estradiol (E(2)) secretion of the controls was replaced by a sustained high level of FSH and a low level of E(2) under galactose toxicity. The ovary developed with apparently normal or deficient complement of follicles. Ovarian response to exogenous gonadotrophin stimulation was blunted, but the response improved significantly when the stimulation was preceded by pituitary desensitization.


CONCLUSIONS
Experimental galactose toxicity may serve as a model for exploring some of the basic tenets of POF.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D004958:Estradiol / Q000097:blood; D005260:Female; D005690:Galactose / Q000097:blood / Q000506:poisoning*; D005695:Galactosephosphates / Q000097:blood; D006062:Gonadotropins / Q000097:blood; D010053:Ovary / Q000473:pathology; D010062:Ovulation Induction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013480:Superovulation; D014621:Vagina / Q000503:physiopathology
D005695:Galactosephosphates; D006062:Gonadotropins; C029973:galactose-1-phosphate; D004958:Estradiol; D005690:Galactose