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Ovotoxic Effects of Galactose Involve Attenuation of Follicle-Stimulating Hormone Bioactivity and Up- Regulation of Granulosa Cell p53 Expression

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Title Ovotoxic Effects of Galactose Involve Attenuation of
Follicle-Stimulating Hormone Bioactivity and Up-
Regulation of Granulosa Cell p53 Expression
 
Creator Banerjee, Sayani
Chakraborty, Pratip
Saha, Piyali
Bandyopadhyay, Soma Aditya
Banerjee, Sutapa
Kabir, Syed N
 
Subject Cell Biology & Physiology
 
Description Clinical evidence suggests an association between galactosaemia and premature ovarian insufficiency (POI); however, the
mechanism still remains unresolved. Experimental galactose toxicity in rats produces an array of ovarian dysfunction
including ovarian development with deficient follicular reserve and follicular resistance to gonadotrophins that characterize
the basic tenets of human POI. The present investigation explores if galactose toxicity in rats attenuates the bioactivity of
gonadotrophins or interferes with their receptor competency, and accelerates the rate of follicular atresia. Pregnant rats
were fed isocaloric food-pellets supplemented with or without 35% D-galactose from day-3 of gestation and continuing
through weaning of the litters. The 35-day old female litters were autopsied. Serum galactose-binding capacity,
galactosyltransferase (GalTase) activity, and bioactivity of FSH and LH together with their receptor competency were
assessed. Ovarian follicular atresia was evaluated in situ by TUNEL. The in vitro effects of galactose were studied in isolated
whole follicles in respect of generation of reactive oxygen species (ROS) and expression of caspase 3, and in isolated
granulosa cells in respect of mitochondrial membrane potential, expression of p53, and apoptosis. The rats prenatally
exposed to galactose exhibited significantly decreased serum GalTase activity and greater degree of galactoseincorporation
capacity of sera proteins. LH biopotency and LH-FSH receptor competency were comparable between the
control and study population, but the latter group showed significantly attenuated FSH bioactivity and increased rate of
follicular atresia. In culture, galactose increased follicular generation of ROS and expression of caspase 3. In isolated
granulosa cells, galactose disrupted mitochondrial membrane potential, stimulated p53 expression, and induced apoptosis
in vitro; however co-treatment with either FSH or estradiol significantly prevented galactose-induced granulosa cell p53
expression. We conclude that the ovotoxic effects of galactose involves attenuation of FSH bioactivity that renders the ovary
resistant to gonadotrophins leading to increased granulosa cell expression of p53 and follicular atresia.
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1538/1/PLOS_ONE___7(2_)_Article_Number_e30709;2012[54].pdf
Banerjee, Sayani and Chakraborty, Pratip and Saha, Piyali and Bandyopadhyay, Soma Aditya and Banerjee, Sutapa and Kabir, Syed N (2012) Ovotoxic Effects of Galactose Involve Attenuation of Follicle-Stimulating Hormone Bioactivity and Up- Regulation of Granulosa Cell p53 Expression. PLoS ONe, 7 (2). e30709.
 
Relation http://dx.doi.org/10.1371/journal.pone.0030709
http://www.eprints.iicb.res.in/1538/