During pregnancy, nutrients are transferred from mother to fetus across the placenta. The mechanisms whereby this occurs, and the adaptations that occur in response to deficiency or overload of iron (Fe) and copper (Cu) are examined in this review. Fe deficiency during pregnancy is common and has serious consequences both in the short and the long term such as fetal growth retardation and cardiovascular problems in the adult offspring. Similarly, Cu deficiency, although not so common, also has deleterious effects. The placenta minimizes the effect of the deficiency by up-regulating the proteins involved in Fe transfer. For example, transferrin receptor levels increase inversely to maternal Fe levels. Divalent metal transporter 1 (DMT1) mRNA in the iron-responsive element (IRE) regulated, but not the non-IRE regulated form is increased, as is the placenta Cu oxidase. Conversely, iron-regulated gene 1 (IREG1) expression is not affected. Fe deficiency increases Cu levels in maternal liver, serum and placenta, but has much less effect in the fetal serum and liver. Apart from maternal ceruloplasmin, mRNA levels of Cu-related proteins are not changed. The Cu oxidase, which we suggest fulfils the function of hephaestin in placenta, is regulated by Cu as well as by Fe. Fe deficiency also has marked effects on cytokine levels in the placenta. Tumor necrosis factor alpha (TNFalpha) and TNFalpha receptor 1 (TNFalphaR1) levels both increase. The data show that altering Fe status has a marked effect on metabolism of other metals and of other important mediators of cell function. This is particularly important during pregnancy, when the developing fetus is very vulnerable to inappropriate micronutrient status.

The objective of this study was to define the physiologic needs of domestic cat embryos to facilitate development of a feline-specific culture medium. In a series of factorial experiments, in vivo-matured oocytes (n = 2040) from gonadotropin-treated domestic cats were inseminated in vitro to generate embryos (n = 1464) for culture. In the initial study, concentrations of NaCl (100.0 vs. 120.0 mM), KCl (4.0 vs. 8.0 mM), KH(2)PO(4) (0.25 vs. 1.0 mM), and the ratio of CaCl(2) to MgSO(4)-7H(2)O (1.0:2.0 mM vs. 2.0:1.0 mM) in the medium were evaluated during Days 1-6 (Day 0: oocyte recovery and in vitro fertilization [IVF]) of culture. Subsequent experiments assessed the effects of varying concentrations of carbohydrate (glucose, 1.5, 3.0, or 6.0 mM; l-lactate, 3.0, 6.0, or 12.0 mM; and pyruvate, 0.1 or 1.0 mM) and essential amino acids (EAAs; 0, 0.5, or 1.0x) in the medium during Days 1-3 and Days 3-6 of culture. Inclusion of vitamins (0 vs. 1.0x) and fetal calf serum (FCS; 0 vs. 5% [v/v]) in the medium also was evaluated during Days 3-6. Development and metabolism of IVF embryos on Day 3 or Day 6 were compared to age-matched in vivo embryos recovered from naturally mated queens. A feline-optimized culture medium (FOCM) was formulated based on these results (100.0 mM NaCl, 8.0 mM KCl, 1.0 mM KH(2)PO(4), 2.0 mM CaCl(2), 1.0 mM MgSO(4), 1.5 mM glucose, 6.0 mM L-lactate, 0.1 mM pyruvate, and 0x EAAs with 25.0 mM NaHCO(3), 1.0 mM alanyl-glutamine, 0.1 mM taurine, and 1.0x nonessential amino acids) with 0.4% (w/v) BSA from Days 0-3 and 5% FCS from Days 3-6. Using this medium, ~70% of cleaved embryos developed into blastocysts with profiles of carbohydrate metabolism similar to in vivo embryos. Our results suggest that feline embryos have stage-specific responses to carbohydrates and are sensitive to EAAs but are still reliant on one or more unidentified components of FCS for optimal blastocyst development.

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Female gonadal steroids differentially modulate expression of ENaC subunit mRNA in the rat kidney.

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