Aldose reductase inhibition prevents galactose-induced ovarian dysfunction in the Sprague-Dawley rat.
OBJECTIVE
Our objective was to determine whether impaired ovarian function induced by short-term creation of a galactosemic state in the rat might be prevented by the coadministration of an aldose reductase inhibitor.


METHODS
Prepubertal Sprague-Dawley rats were fed four different diets including (1) control, (2) 40% galactose, (3) 40% galactose and an aldose reductase inhibitor, and (4) an aldose reductase inhibitor with the control diet. Percentage germinal vesicle breakdown, postovulatory oocyte quantities, hormonal parameters, ovarian histologic evaluation, and ovarian galactitol concentrations were determined.


RESULTS
The galactose-fed animals (group 2) had decreased germinal vesicle breakdown (47%) versus control (69%, p < 0.05). Galactose-exposed animals had significantly decreased quantities of postovulatory eggs (6.4 per animal) after menotropin ovarian stimulation in comparison with controls (14.1, p < 0.01). In rats exposed to high dietary levels of galactose (group 2) ovarian galactitol concentrations were significantly higher (protein 42.12 mumol/gm versus 0.0 for controls, p < 0.005). When galactose-fed animals received the aldose reductase inhibitor, ovarian accumulation of galactitol was significantly reduced and the observed detrimental effects on the oocyte were prevented.


CONCLUSIONS
Galactitol accumulation or metabolic flux through aldose reductase in galactosemic rodents may be involved in the demonstrated ovarian dysfunction.
Meyer
W R
WR
Yale-New Haven Hospital, Yale University School of Medicine, New Haven, Connecticut.
Doyle
M B
MB
Grifo
J A
JA
Lipetz
K J
KJ
Oates
P J
PJ
DeCherney
A H
AH
Diamond
M P
MP
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D005260:Female; D004376:Galactitol / Q000378:metabolism; D005690:Galactose / Q000494:pharmacology; D006107:Granulosa Cells / Q000473:pathology; D010049:Ovarian Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004376:Galactitol; D000449:Aldehyde Reductase; D005690:Galactose