Maternal hypothyroidism in the rat influences placental and liver glycogen stores: fetal growth retardation near term is unrelated to maternal and placental glucose metabolic compromise.
Maternal hypothyroidism impairs fetal growth in the rat, but the mechanisms by which this occurs are unknown. Since the fetus derives its glucose supply from the mother, and maternal thyroidectomy may disturb maternal and placental glucose metabolism, we postulated that maternal and/or placental glucose metabolic compromise may contribute to fetal growth retardation in hypothyroid dams. Feto-placental growth, tissue glycogen stores and glucose levels in sera and amniotic fluid were determined in rat dams partially thyroidectomized (TX) before pregnancy and in euthyroid controls. Fetal body weight at 16, 19 and 21 days gestation (d.g.) was related to pre-mating maternal serum total thyroxine (TT(4)) levels; permanent fetal growth retardation occurred in severely (TX(s); pre-mating maternal serum TT(4)<or=16.19 nM) - but not in moderately (TX(m)) - hypothyroid dams. In TX(s) dams, glycogen concentration was elevated in maternal liver and in the fetal side of the placenta at 16 and 19 d.g., and in the maternal side of the placenta at 19 and 21 d.g., despite maternal euglycemia. In contrast, fetal liver glycogen concentration was deficient in TX(m) dams at 19 d.g. and in TX(s) dams at 19 and 21 d.g., and fetal hypoglycemia occurred in TX(s) dams at 21 d.g. Multiple regression analyses indicate that these fetal deficits are strongly associated with the retardation in fetal growth, while the elevated maternal liver and placental glycogen concentrations have no impact on fetal growth near term. The mechanisms by which severe maternal hypothyroidism permanently retards rat fetal growth remain to be determined.
Pickard
M R
MR
Division of Molecular Endocrinology, University College London Medical School, Mortimer Street, London W1T 3AA, UK.
Leonard
A J
AJ
Ogilvie
L M
LM
Edwards
P R
PR
Evans
I M
IM
Sinha
A K
AK
Ekins
R P
RP
D000653:Amniotic Fluid / Q000737:chemistry; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005865:Gestational Age; D005947:Glucose / Q000032:analysis; D006003:Glycogen / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D013974:Thyroxine / Q000097:blood
D001786:Blood Glucose; D006003:Glycogen; D005947:Glucose; D013974:Thyroxine