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

Content Provider	Springer Nature : BioMed Central
Author	Kaczmarek, Monika M. Mendoza, Tamra Kozak, Leslie P.
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.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-016-2615-4.pdf
Ending Page	18
Page Count	18
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/s12864-016-2615-4
Journal	BMC Genomics
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2016-05-04
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Hypothalamus Kisspeptin Leptin Reproductive performance Multigenerational programming
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

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