Effects of exogenous progesterone on the expression of mineral regulatory molecules by ovine endometrium and placentomes†.

This study aimed to determine whether the acceleration of conceptus development induced by the administration of exogenous progesterone (P4) during the preimplantation period of pregnancy alters calcium, phosphate, and vitamin D signaling at the maternal-conceptus interface. Suffolk ewes (n = 48) were mated to fertile rams and received daily intramuscular injections of either corn oil (CO) vehicle or 25 mg of progesterone in CO (P4) for the first 8 days of pregnancy and hysterectomized on either Day 9 (CO, n = 5; P4, n = 6), 12 (CO, n = 9; P4, n = 4) or 125 (CO, n = 14; P4, n = 10) of gestation. The expression of S100A12 (P < 0.05) and fibroblast growth factor receptor (FGFR2) (P < 0.01) messenger RNAs (mRNAs) was lower in endometria from P4-treated ewes on Day 12. The expression of ADAM10 (P < 0.05) mRNA was greater in endometria from P4-treated ewes on Day 125. The expression of ADAM10 (P < 0.01), FGFR2 (P < 0.05), solute carrier (SLC)20A1 (P < 0.05), TRPV5 (P < 0.05), and TRPV6 (P < 0.01) mRNAs was greater, but KL mRNA expression was lower (P < 0.05) in placentomes from P4-treated ewes at Day 125. There was lower endometrial and greater placentomal expression of mRNAs involved in mineral metabolism and transport in twin compared to singleton pregnancies. Further, the expression of mRNAs involved in mineral metabolism and transport was greater in P4-treated twin placentomes. KL, FGF23, vitamin D receptor (VDR), S100A9, S100A12, S100G, and CYP27B1 proteins were immunolocalized in endometria and placentomes. Exogenous P4 in early pregnancy altered the expression of regulators of calcium, phosphate, and vitamin D on Day 125 of pregnancy indicating a novel effect of P4 on mineral transport at the maternal-conceptus interface.

Pre-implantation exogenous progesterone and pregnancy in sheep: I. polyamines, nutrient transport, and progestamedins.

BACKGROUND: Administration of exogenous progesterone (P4) to ewes during the pre-implantation period advances conceptus development and implantation. This study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus development. Pregnant ewes (n = 38) were treated with either 25 mg P4 in 1 mL corn oil (P4, n = 18) or 1 mL corn oil alone (CO, n = 20) from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of pregnancy. Endometrial expression of genes encoding enzymes for synthesis of polyamines, transporters of glucose, arginine, and glycine, as well as progestamedins was determined by RT-qPCR. RESULTS: On day 12 of pregnancy, conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were spherical. The mRNA expression of AZIN2, an arginine decarboxylase, was lower in endometria of P4-treated than CO-treated ewes on day 9 of pregnancy. Expression of FGF10, a progestamedin, was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of gestation. Treatment with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of pregnancy. CONCLUSIONS: Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10, which may accelerate proliferation of trophectoderm cells, but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme AZIN2. Further research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss.

Obesity increases hepatic glycine dehydrogenase and aminomethyltransferase expression while dietary glycine supplementation reduces white adipose tissue in Zucker diabetic fatty rats.

Obesity is associated with altered glycine metabolism in humans. This study investigated the mechanisms regulating glycine metabolism in obese rats. Eight-week-old Zucker diabetic fatty rats (ZDF; a type-II diabetic animal model) received either 1% glycine or 1.19% L-alanine (isonitrogenous control) in drinking water for 6 weeks. An additional group of lean Zucker rats also received 1.19% L-alanine as a lean control. Glycine concentrations in serum and liver were markedly lower in obese versus lean rats. Enteral glycine supplementation restored both serum and hepatic glycine levels, while reducing mesenteric and internal white fat mass compared with alanine-treated ZDF rats. Blood glucose and non-esterified fatty acid (NEFA) concentrations did not differ between the control and glycine-supplemented ZDF rats (P > 0.10). Both mRNA and protein expression of aminomethyltransferase (AMT) and glycine dehydrogenase, decarboxylating (GLDC) were increased in the livers of obese versus lean rats (P < 0.05). In contrast, glycine cleavage system H (GCSH) hepatic mRNA expression was downregulated in obese versus lean rats, although there was no change in protein expression. These findings indicate that reduced quantities of glycine observed in obese subjects likely results from an upregulation of the hepatic glycine cleavage system and that dietary glycine supplementation potentially reduces obesity in ZDF rats.

Nutrition and reproduction: links to epigenetics and metabolic syndrome in offspring.

PURPOSE OF REVIEW: Inappropriate exposure of gametes and/or products of conception to nutritional imbalance alters critical metabolic set points in the offspring and increases propensity to disease. This review will focus on recent findings highlighting clear links to epigenetic modifications in response to dietary manipulations as well as nutritional strategies with the potential to mitigate the effects of an otherwise poor nutritional environment. RECENT FINDINGS: Maternal nutritional imbalance, either through global nutritional manipulation or deficiencies in select nutrients, predisposes the offspring to metabolic disease. Disease susceptibility is linked to global and/or specific modifications of the epigenome at key metabolic regulatory genes. Paternal nutritional imbalance also increases the likelihood of metabolic disease in offspring through similar epigenetic mechanisms. Finally, dietary intervention with select nutrients has been shown to ameliorate postnatal disease phenotypes in offspring, although the exact molecular mechanisms have not been elucidated. SUMMARY: Select nutrients, such as amino acids and vitamins, not only serve as building blocks for growth but also mediate a myriad of physiological functions, including providing substrates for DNA synthesis. These nutrients hold great promise as intervention strategies to combat a suboptimal developmental environment.

Regulation of brown adipose tissue development and white fat reduction by L-arginine.

PURPOSE OF REVIEW: Brown adipose tissue (BAT), which is present in humans, plays an important role in oxidation of fatty acids and glucose. The purpose of this review is to highlight an important role for L-arginine in regulating BAT growth and development, thereby reducing obesity in mammals. RECENT FINDINGS: Dietary supplementation with L-arginine reduces white adipose tissue in genetically or diet-induced obese rats, obese pregnant sheep, and obese humans with type II diabetes. L-arginine treatment enhances BAT growth in both fetuses and postnatal animals. At molecular and cellular levels, L-arginine stimulates expression of peroxisome proliferator-activated receptor-γ coactivator 1 (the master regulator of mitochondrial biogenesis), nitric oxide synthase, heme oxygenase, and adenosine monophosphate-activated protein kinase. At the whole body level, L-arginine increases blood flow to insulin-sensitive tissues, adipose tissue lipolysis, and the catabolism of glucose and fatty acids, but inhibits fatty acid synthesis and ameliorates oxidative stress, thereby improving metabolic profile. SUMMARY: L-arginine increases mammalian BAT growth and development via mechanisms involving gene expression, nitric oxide signaling, and protein synthesis. This enhances the oxidation of energy substrates and, thus, reduces white fat accretion in the body. L-arginine holds great promise in preventing and treating obesity in humans.