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In the cow, inadequate concentrations of progesterone during gestation may lead to an abrupt termination of pregnancy. The primary organ involved in progesterone catabolism is the liver, which contains an abundance of cytochrome P450 isozymes (EC 1.14.14.1; mixed-function monooxygenases). The objectives of the current experiment were to determine the effect of feeding 2 isoenergetic and isonitrogenous diets, formulated to cause divergent insulin secretion, on hepatic cytochrome P450 2C (CYP2C) and 3A (CYP3A) activity as well as the resulting biological half-life of progesterone. Twenty-two Holstein cows averaging 80+/-7 d in milk were randomly assigned to either a high cornstarch diet or a high fiber diet in a crossover experimental design consisting of two 14-d periods. Dry matter intake, milk yield, milk lactose yield, and milk lactose percentage were similar between the 2 diets. Milk fat yield and milk fat percentage were higher in cows fed the high fiber diet, whereas milk protein yield tended to be higher and milk protein percentage was higher in cows fed the high cornstarch diet. Energy balance tended to be improved by 57% in cows consuming the high cornstarch diet. Insulin concentrations at the time of liver biopsy (3.16+/-0.04h post-feeding) were increased by 44% in cows consuming the high cornstarch diet compared with cows consuming the high fiber diet. Cytochrome P450 2C activity was decreased by 45%, whereas CYP3A activity tended to be lowered by 34% in cows consuming the high cornstarch diet. Cytochrome P450 2C mRNA expression tended to be decreased by 21% in cows fed the high cornstarch diet, whereas CYP3A mRNA expression was not different between the dietary treatments. The fractional rate constant of progesterone decay was not different between the 2 diets; however, the half-life of progesterone tended to be longer in cows fed the high cornstarch diet compared with cows fed the high fiber diet (85 vs. 64min, respectively). In summary, cows consuming the high cornstarch diet had increased insulin concentrations and lower hepatic CYP2C and CYP3A activity and tended to have a longer progesterone half-life compared with cows consuming the high fiber diet. Feeding diets that stimulate insulin secretion could alter progesterone clearance during lactation, when dairy cows have increased rates of progesterone inactivation because of high energy demands and increased DMI.

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Background Placental efficiency (PE) describes the relationship between placental and fetal weights (fetal wt/placental wt). Within litters, PE can vary drastically, resulting in similarly sized pigs associated with differently sized placentas, up to a 25% weight difference. However, the mechanisms enabling the smaller placenta to grow a comparable littermate are unknown. To elucidate potential mechanisms, morphological measurements and gene expression profiles in placental and associated endometrial tissues of high PE and low PE feto-placental units were compared. Tissue samples were obtained from eight maternal line gilts during gestational day 95 ovario-hysterectomies. RNA was extracted from tissues of feto-placental units with the highest and lowest PE in each litter and sequenced. Results Morphological measurements, except placental weight, were not different ( P > 0.05) between high and low PE. No DEG were identified in the endometrium and 214 DEG were identified in the placenta (FDR < 0.1), of which 48% were upregulated and 52% were downregulated. Gene ontology (GO) analysis revealed that a large percentage of DEG were involved in catalytic activity, binding, transporter activity, metabolism, biological regulation, and localization. Four GO terms were enriched in the upregulated genes and no terms were enriched in the downregulated genes (FDR < 0.05). Eight statistically significant correlations ( P < 0.05) were identified between the morphological measurements and DEG. Conclusion Morphological measures between high and low PE verified comparisons were of similarly sized pigs grown on different sized placentas, and indicated that any negative effects of a reduced placental size on fetal growth were not evident by day 95. The identification of DEG in the placenta, but absence of DEG in the endometrium confirmed that the placenta responds to the fetus. The GO analyses provided evidence that extremes of PE are differentially regulated, affecting components of placental transport capacity like nutrient transport and blood flow. However, alternative GO terms were identified, indicating the complexity of the relationship between placental and fetal weights. These findings support the use of PE as a marker of placental function and provide novel insight into the genetic control of PE, but further research is required to make PE production applicable.

Research in the area of fetal programming has focused on intrauterine growth restriction. Few studies have attempted to examine programming mechanisms that ultimately lead to lambs with a greater potential for postnatal growth. We previously demonstrated that treatment of ewes with GH at the time of breeding led to an increase in birth weight. Therefore, the objective of this study was to determine the effects of a single injection of sustained-release GH given during the periconceptional period on fetal growth and development and to determine if the GH axis would be altered in these offspring. Estrus was synchronized using 2 injections of PGF(2alpha); at the time of the second injection, ewes assigned to treatment were also given an injection of sustained-release GH. A maternal jugular vein sample was taken weekly to analyze IGF-I as a proxy for GH to estimate the duration of the treatment effect. In ewes treated with GH, IGF-I increased (P < 0.05) by wk 1 and remained elevated until wk 4 postinjection. Lambs were weighed, crown-rump length and abdominal girth were determined, and a plasma sample was collected. In a subset of male lambs, liver, heart, and brain weights were obtained, as well as left and right ventricular wall thicknesses. On postnatal d 100, a subset of ewe lambs were weighed and challenged with an intravenous injection of GHRH. Lambs from treated ewes had increased (P < 0.05) birth weight and abdominal girth compared with control lambs; however, there was no difference in crown-rump length. Expression of GH receptor and IGF-I were increased (P < 0.05) in lambs gestated by GH-treated ewes compared with control ewes. The left ventricular wall was thinner (P < 0.05) from lambs in the GH-treated group compared with control lambs. On postnatal d 100, those ewe lambs born to ewes treated with GH continued to be heavier (P < 0.05) and had no IGF-I response to GHRH challenge. In conclusion, treating ewes with a single injection of GH appeared to alter fetal growth and development. Lambs born to ewes treated with GH were larger at birth and had altered organ development, which may indicate that early maternal GH treatment may lead to permanent changes in the developing fetus. The ewe lambs maintained their growth performance to at least 100 d of postnatal life and appeared to have an altered GH axis, as demonstrated by the altered response to GHRH.