Melatonin supplementation alters uteroplacental hemodynamics and fetal development in an ovine model of intrauterine growth restriction

Lemley, Caleb O; Meyer, Allison M; Camacho, Leticia E.; Neville, Tammi L; Newman, David J.; Caton, J. S.; Vonnahme, K. A.

doi:10.1152/ajpregu.00407.2011

Cited by 111 publications

(124 citation statements)

References 64 publications

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“…As expected, and previously reported (Lemley et al, 2012), nutrient restriction decreased (P < 0.001) maternal BW (Table 1). Nutrient restriction decreased (P ⩽ 0.001) maternal pancreas weight (g) and melatonin supplementation increased (P = 0.03) maternal pancreas weight (g) with a tendency (P = 0.05) for an increase in pancreas weight when expressed as g/kg BW.…”

Section: Resultssupporting

confidence: 91%

“…As previously described, fetal BW decreased (P < 0.01) with nutrient restriction but was not influenced by melatonin supplementation (Lemley et al, 2012; Table 3). Fetal pancreatic weight, protein concentration, and α-amylase, trypsin and lipase activity were not influenced by nutrient restriction or melatonin supplementation.…”

Section: Resultssupporting

confidence: 82%

“…Animal care and dietary treatments were described previously (Lemley et al, 2012). Briefly, 32 nulliparous ewes carrying singletons were selected for the study; however, one ewe was removed due to a perforated esophagus, which existed before dietary treatment.…”

Section: Animals and Dietary Treatmentsmentioning

confidence: 99%

“…The day before feeding, 100 g of the control pellet was placed into a small plastic bag and top dressed with 1 ml of melatonin solution. The ethanol was allowed to evaporate overnight at room temperature in complete darkness before feeding (Lemley et al, 2012). The amount of feed offered to individual ewes was adjusted weekly based on BW and change in BW to ensure the desired average daily gains were achieved (Reed et al, 2007).…”

Section: Animals and Dietary Treatmentsmentioning

confidence: 99%

“…Understanding the influence of maternal nutrition on fetal development provides the potential to design supplementation strategies that may help overcome these negative impacts. Melatonin, most widely known for its role in regulating circadian rhythms, has been shown to increase utero-placental blood flow when supplemented to pregnant ewes which has the potential to reduce or offset the negative effects of nutrient restriction on maternal blood flow and return utero-placental nutrient transfer to normal levels (Lemley et al, 2012). Melatonin can be synthesized by many tissues of the body with the largest source being produced in the gastrointestinal tract (GIT; Jaworek et al, 2007 and.…”

Section: Introductionmentioning

confidence: 99%

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Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

Keomanivong

Lemley

Camacho

et al. 2016

Animal

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Primiparous ewes ( n = 32) were assigned to dietary treatments in a 2 × 2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. Treatments consisted of nutrient intake with 60% (RES) or 100% (ADQ) of requirements and melatonin supplementation at 0 (CON) or 5 mg/day (MEL). Treatments began on day 50 of gestation and continued until day 130. On day 130, blood was collected under general anesthesia from the uterine artery, uterine vein, umbilical artery and umbilical vein for plasma insulin analysis. Ewes were then euthanized and the pancreas removed from the ewe and fetus, trimmed of mesentery and fat, weighed and snap-frozen until enzyme analysis. In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. Nutrient restriction decreased ( P ⩽ 0.001) maternal pancreatic mass (g) and α-amylase activity (U/g, kU/pancreas, U/kg BW). Ewes supplemented with melatonin had increased pancreatic mass ( P = 0.03) and α-amylase content (kU/pancreas and U/kg BW). Melatonin supplementation decreased ( P = 0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster ( P = 0.04). Nutrient restriction decreased pancreatic insulin-positive tissue area ( P = 0.03) and percent of large (32 001 to 512 000 µm 2 ) and giant (⩾512 001 µm 2 ) insulin-containing cell clusters ( P = 0.04) in the fetus. Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater ( P ⩽ 0.01) in animals receiving 100% requirements. When comparing ewes to fetuses, ewes had a greater percentage of medium insulin-containing cell clusters (2001 to 32 000 µm 2 ) while fetuses had more ( P < 0.001) pancreatic insulin-positive area (relative to section of tissue) and a greater percent of small, large and giant insulin-containing cell clusters ( P ⩽ 0.02). Larger insulin-containing clusters were observed in fetuses ( P < 0.001) compared with ewes. In summary, the maternal pancreas responded to nutrient restriction by decreasing pancreatic weight and activity of digestive enzymes while melatonin supplementation increased α-amylase content. Nutrient restriction decreased the number of pancreatic insulin-containing clusters in fetuses while melatonin supplementation did not influence insulin concentration. This indicated using melatonin as a therapeutic agent to mitigate reduced pancreatic function in the fetus due to maternal nutrient restriction may not be beneficial.Keywords: development, ewes, melatonin, nutrient restriction, pancreas ImplicationsMelatonin is a potential therapeutic to overcome negative effects of nutrient restriction during pregnancy because of its roles in regulating blood flow and gastr...

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 82%

Section: Animals and Dietary Treatmentsmentioning

confidence: 99%

Section: Animals and Dietary Treatmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

Keomanivong

Lemley

Camacho

et al. 2016

Animal

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Treatment of poor placentation and the prevention of associated adverse outcomes – what does the future hold?

2014

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Poor placentation, which manifests as pre-eclampsia and fetal growth restriction, is a major pregnancy complication. The underlying cause is a deficiency in normal trophoblast invasion of the spiral arteries, associated with placental inflammation, oxidative stress, and an antiangiogenic state. Peripartum therapies, such as prenatal maternal corticosteroids and magnesium sulphate, can prevent some of the adverse neonatal outcomes, but there is currently no treatment for poor placentation itself. Instead, management relies on identifying the consequences of poor placentation in the mother and fetus, with iatrogenic preterm delivery to minimise mortality and morbidity. Several promising therapies are currently under development to treat poor placentation, to improve fetal growth, and to prevent adverse neonatal outcomes. Interventions such as maternal nitric oxide donors, sildenafil citrate, vascular endothelial growth factor gene therapy, hydrogen sulphide donors, and statins address the underlying pathology, while maternal melatonin administration may provide fetal neuroprotection. In the future, these may provide a range of synergistic therapies for pre-eclampsia and fetal growth restriction, depending on the severity and gestation of onset.

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Maternal Undernutrition and Long-Term Effects on Hepatic Function

Hardy

2017

Diet, Nutrition, and Fetal Programming

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Melatonin supplementation alters uteroplacental hemodynamics and fetal development in an ovine model of intrauterine growth restriction

Abstract: Lemley CO, Meyer AM, Camacho LE, Neville TL, Newman DJ, Caton JS, Vonnahme KA. Melatonin supplementation alters uteroplacental hemodynamics and fetal development in an ovine model of intrauterine growth restriction.

Cited by 111 publications

References 64 publications

Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

Treatment of poor placentation and the prevention of associated adverse outcomes – what does the future hold?

Maternal Undernutrition and Long-Term Effects on Hepatic Function

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