Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): Exposure and toxicokinetics prior to and during pregnancy

Burbacher, Thomas M.; Shen, Danny D.; Lalovic, Bojan; Grant, Kimberly S.; Sheppard, Lianne; Damian, Doris; Ellis, Sean; Liberato, Noelle

doi:10.1016/j.ntt.2003.10.003

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…; Burbacher et al. ; McCurdy ). The need for data in primate pregnancy to translate to the human situation is evident from observed differences in the one‐carbon and methionine cycle pathways between rodents and primates.…”

Section: Introductionmentioning

confidence: 99%

“…folate, vitamin B-12, choline, and betaine) to several important metabolic processes (Kalhan and Marczewski 2012) including those involved in developmental programming. While there are studies showing disturbances in the methionine cycle and gene specific DNA methylation as a result of maternal nutritional imbalances in rodent pregnancy (Lillycrop et al 2010), few studies have been conducted in pregnant nonhuman primates (Blocker et al 1989;Burbacher et al 2004;McCurdy 2009). The need for data in primate pregnancy to translate to the human situation is evident from observed differences in the one-carbon and methionine cycle pathways between rodents and primates.…”

Section: Introductionmentioning

confidence: 99%

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Maternal obesity disrupts the methionine cycle in baboon pregnancy

et al. 2015

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Maternal intake of dietary methyl-micronutrients (e.g. folate, choline, betaine and vitamin B-12) during pregnancy is essential for normal maternal and fetal methionine metabolism, and is critical for important metabolic processes including those involved in developmental programming. Maternal obesity and nutrient excess during pregnancy influence developmental programming potentially predisposing adult offspring to a variety of chronic health problems. In the present study, we hypothesized that maternal obesity would dysregulate the maternal and fetal methionine cycle. To test this hypothesis, we developed a nulliparous baboon obesity model fed a high fat, high energy diet (HF-HED) prior to and during gestation, and examined methionine cycle biomarkers (e.g., circulating concentrations of homocysteine, methionine, choline, betaine, key amino acids, folate, and vitamin B-12). Animals were group housed allowing full physical activity and social interaction. Maternal prepregnancy percent body fat was 5% in controls and 19% in HF-HED mothers, while fetal weight was 16% lower in offspring of HF-HED mothers at term. Maternal and fetal homocysteine were higher, while maternal and fetal vitamin B-12 and betaine were lower in the HF-HED group. Elevations in circulating maternal folate were evident in the HF-HED group indicating impaired folate metabolism (methyl-trap) as a consequence of maternal vitamin B-12 depletion. Finally, fetal methionine, glycine, serine, and taurine were lower in the HF-HED fetuses. These data show that maternal obesity disturbs the methionine cycle in primate pregnancy, providing a mechanism for the epigenetic changes observed among obese pregnant women and suggesting diagnostic and therapeutic opportunities in human pregnancies complicated by obesity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Maternal obesity disrupts the methionine cycle in baboon pregnancy

et al. 2015

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“…Repeated inhalational exposure to methanol resulted in increased methanol serum levels and increased methanol metabolism and clearance after 90 days in all subjects. Pregnancy did not affect this increase, blood clearance, or elimination half‐life . Taken together, extrapolation of the teratogenic effects of methanol seen in animal studies to humans is challenging.…”

Section: Pregnancymentioning

confidence: 91%

Folate as an Adjuvant Therapy in Methanol Poisoning

Theobald

Lim

2019

Nut in Clin Prac

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Folate and its derivatives have long been used as an adjunctive treatment in methanol poisoning. Methanol is ultimately metabolized to formate, the toxic compound. The accumulation of formate can lead to acidemia, retinal damage, visual impairment, and death. Formate is converted to carbon dioxide and water in a folate-dependent manner, and folate is often given in cases of methanol poisoning. In this paper, the evidence for folate as an adjunctive therapy in methanol poisoning is reviewed. (Nutr Clin Pract.

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“…Adult female Macaca fascicularis monkeys were exposed to 0, 200, 600 or 1,800 ppm MeOH vapor for approximately 2.5 hours/day, 7 days/week [Burbacher et al, 2004a]. Methanol exposure did not alter menstrual cycles, conception rate or birth status outcomes [Burbacher et al, 2004b]. The mean length of pregnancy was however, reduced in MeOH-exposed females by 6–8 days when compared to control monkeys.…”

Section: Research In Reproductive and Developmental Sciences At The Iprlmentioning

confidence: 99%

“…If methanol-based fuels are adopted as a new energy source, the potential exists for widespread public exposure to vapors, including sensitive subgroups such as pregnant women, infants and the elderly [Carson et al, 1987]. Results from studies conducted at the IPRL demonstrated that MeOH exposure did not alter adult female menstrual cycles, conception rate or birth status outcomes [Burbacher et al, 2004b]. Infants born to MeOH-exposed females were normal in birthweight and showed no evidence of physical birth malformations.…”

Section: Environmental Chemicalsmentioning

confidence: 99%

Four decades of leading‐edge research in the reproductive and developmental sciences: The Infant Primate Research Laboratory at the University of Washington National Primate Research Center

Burbacher

Grant

Worlein

et al. 2013

American J Primatol

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The Infant Primate Research Laboratory (IPRL) was established in the 1970s at the University of Washington as a visionary project of Dr. Gene (Jim) P. Sackett. Supported by a collaboration between the Washington National Primate Research Center and the Center on Human Health and Disability, the IPRL operates under the principle that learning more about the causes of abnormal development in macaque monkeys will provide important insights into mechanisms underlying childhood neurodevelopmental disorders. Over the past forty years, a broad range of research projects have been conducted at the IPRL. Some have described the normal expression of species-typical behaviors in nursery-reared macaques while others have focused on specific issues in perinatal medicine and research. This article will review the unique history of the IPRL and the scientific contributions produced by research conducted in the laboratory. Past and present investigations at the IPRL have explored the consequences of adverse early rearing, low-birth-weight, prematurity, epilepsy, chemical/drug exposure, viral infection, diarrheal disease, vaccine safety, assisted reproductive technologies and perinatal hypoxia on growth and development. New directions of investigation include the production of a transgenic primate model using our embryonic stem cell-based technology to better understand and treat heritable forms of human mental retardation such as fragile X.

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Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): Exposure and toxicokinetics prior to and during pregnancy

Cited by 7 publications

References 39 publications

Maternal obesity disrupts the methionine cycle in baboon pregnancy

Maternal obesity disrupts the methionine cycle in baboon pregnancy

Folate as an Adjuvant Therapy in Methanol Poisoning

Four decades of leading‐edge research in the reproductive and developmental sciences: The Infant Primate Research Laboratory at the University of Washington National Primate Research Center

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