Dataset Information

Lactation undernutrition leads to multigenerational molecular programming of hypothalamic gene networks controlling reproduction.

ABSTRACT:

Background

Reproductive success is dependent on development of hypothalamic circuits involving many hormonal systems working in concert to regulate gonadal function and sexual behavior. The timing of pubertal initiation and progression in mammals is likely influenced by the nutritional and metabolic state, leading us to the hypothesis that transient malnutrition experienced at critical times during development may perturb pubertal progression through successive generations. To test this hypothesis we have utilized a mouse model of undernutrition during suckling by exposing lactating mothers to undernutrition.

Results

Using a combination of transcriptomic and biological approaches, we demonstrate that molecular programming of hypothalamus may perturb gender specific phenotypes across generations that are dependent on the nutritional environment of the lactation period. Lactation undernutrition in first (F1) generation offspring affected body composition, reproductive performance parameters and influenced the expression of genes responsible for hypothalamic neural circuits controlling reproductive function of both sexes. Strikingly, F2 offspring showed phenotypes similar to F1 progeny; however, they were sex and parental nutritional history specific. Here, we showed that deregulated expression of genes involved in kisspeptin signaling within the hypothalamus is strongly associated with a delay in the attainment of puberty in F1 and F2 male and female offspring.

Conclusion

The early developmental plasticity of hypothalamus when challenged with undernutrition during postnatal development not only leads to altered expression of genes controlling hypothalamic neural circuits, altered body composition, delayed puberty and disturbed reproductive performance in F1 progeny, but also affects F2 offspring, depending on parental malnutrition history and in sexually dimorphic manner.

SUBMITTER: Kaczmarek MM

PROVIDER: S-EPMC4857247 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Lactation undernutrition leads to multigenerational molecular programming of hypothalamic gene networks controlling reproduction.

Kaczmarek Monika M MM Mendoza Tamra T Kozak Leslie P LP

BMC genomics 20160504

<h4>Background</h4>Reproductive success is dependent on development of hypothalamic circuits involving many hormonal systems working in concert to regulate gonadal function and sexual behavior. The timing of pubertal initiation and progression in mammals is likely influenced by the nutritional and metabolic state, leading us to the hypothesis that transient malnutrition experienced at critical times during development may perturb pubertal progression through successive generations. To test this ...[more]

PMID: 27146259

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Project description:BackgroundMaternal undernutrition programs fetal energy homeostasis and increases the risk of metabolic disorders later in life. This study aimed to identify the signs of hepatic metabolic programming in utero and during the juvenile phase after intrauterine undernutrition during midgestation.MethodsFifty-three pregnant goats were assigned to the control (100% of the maintenance requirement) or restricted (60% of the maintenance requirement from day 45 to day 100 of midgestation and realimentation thereafter) group to compare hepatic energy metabolism in the fetuses (day 100 of gestation) and kids (postnatal day 90).ResultsUndernutrition increased the glucagon concentration and hepatic hexokinase activity, decreased the body weight, liver weight and hepatic expression of G6PC, G6PD, and PGC1α mRNAs, and tended to decrease the hepatic glycogen content and ACOX1 mRNA level in the dams. Maternal undernutrition decreased the growth hormone (GH) and triglyceride concentrations, tended to decrease the body weight and hepatic hexokinase activity, increased the hepatic PCK1, PCK2 and PRKAA2 mRNAs levels and glucose-6-phosphatase activity, and tended to increase the hepatic PRKAB1 and CPT1α mRNAs levels in the male fetuses. In the restricted female fetuses, the hepatic hexokinase activity and G6PC mRNA level tended to be increased, but PKB1 mRNA expression was decreased and the ACACA, CPT1α, NR1H3 and STK11 mRNA levels tended to be decreased. Maternal undernutrition changed the hepatic metabolic profile and affected the metabolic pathway involved in amino acid, glycerophospholipid, bile acid, purine, and saccharide metabolism in the fetuses, but not the kids. Additionally, maternal undernutrition increased the concentrations of GH and cortisol, elevated the hepatic glucose-6-phosphate dehydrogenase activity, and tended to decrease the hepatic glycogen content in the male kids. No alterations in these variables were observed in the female kids.ConclusionsMaternal undernutrition affects the metabolic status in a sex- and stage-specific manner by changing the metabolic profile, expression of genes involved in glucose homeostasis and enzyme activities in the liver of the fetuses. The changes in the hormone levels in the male fetuses and kids, but not the female offspring, represent a potential sign of metabolic programming.

Dataset Information

Lactation undernutrition leads to multigenerational molecular programming of hypothalamic gene networks controlling reproduction.

Background

Results

Conclusion

Publications

Lactation undernutrition leads to multigenerational molecular programming of hypothalamic gene networks controlling reproduction.

Similar Datasets

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