Changes in secretory cell turnover, and mitochondrial oxidative damage in the mouse mammary gland during a single prolonged lactation cycle suggest the possibility of accelerated cellular aging

Hadsell, Darryl L.; Torres, Daniel; George, Jessy; Capuco, Anthony; Ellis, S.E.; Fiorotto, Marta L.

doi:10.1016/j.exger.2005.12.005

Cited by 26 publications

(32 citation statements)

References 57 publications

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“…Previous work in our laboratory has made use of a litter cross-fostering model in the lactating mouse to study the cellular and biochemical changes that are associated with the known temporal variations that occur during a normal lactation and with prolonged lactation (26). The results of that study suggested that alterations in mitochondrial oxidative damage might be linked to temporal changes in milk production during the lactation cycle.…”

mentioning

confidence: 62%

“…The animals were analyzed in their first lactation, and none were concurrently pregnant during the course of these studies. To maintain constant suckling stimulus, the litters were initially normalized to 10 pups/litter, and a set of 8-day-old pups was cross-fostered onto the dams every week as previously described (26). At the time of harvesting, wet weights were obtained for the mammary glands.…”

Section: Methodsmentioning

confidence: 99%

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Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle

Hadsell

Olea

Wei

et al. 2011

Physiological Genomics

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Hadsell DL, Olea W, Wei J, Fiorotto ML, Matsunami RK, Engler DA, Collier RJ. Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle. Physiol Genomics 43: 271-285, 2011. First published December 28, 2010 doi:10.1152/physiolgenomics.00133.2010.-The regulation of mitochondrial biogenesis and function in the lactating mammary cell is poorly understood. The goal of this study was to use proteomics to relate temporal changes in mammary cell mitochondrial function during lactation to changes in the proteins that make up this organelle. The hypothesis tested was that changes in mammary cell mitochondrial biogenesis and function during lactation would be accounted for by coordinated changes in the proteins of the electron transport chain and that some of these proteins might be linked by their expression patterns to PPARGC1␣ and AMP kinase. The mitochondrial proteome was studied along with markers of mitochondrial biogenesis and function in mammary tissue collected from mice over the course of a single prolonged lactation cycle. Mammary tissue concentrations of AMP and ADP were increased (P Ͻ 0.05) during early lactation and then declined with prolonged lactation. Similar changes were also observed for mitochondrial ATP synthesis activity, mitochondrial mass and DNA copy number. Analysis of the mammary cell mitochondrial proteome identified 244 unique proteins. Of these, only two proteins of the electron transport chain were found to increase during early lactation. In contrast, coordinated changes in numerous electron transport chain proteins were observed both during mid-and late lactation. There were six proteins that could be directly linked to PPARGC1␣ through network analysis. Abundance of PPARGC-1␣ and phosphorylation of AMP kinase was highest on day 2 postpartum. The results suggest that the increases in mammary mitochondria ATP synthesis activity during early lactation results from changes in only a limited number proteins. In addition, decreases in a handful of proteins linked to lipid oxidation could be temporally linked to decreases in PPARGC1␣ and phospho-AMP kinase suggesting potential roles for these proteins in coordinating mammary gland metabolism during early lactation. mitochondria; proteome; adenosine 5=-triphosphate

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mentioning

confidence: 62%

Section: Methodsmentioning

confidence: 99%

Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle

Hadsell

Olea

Wei

et al. 2011

Physiological Genomics

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“…In addition, litter weights were equalized across all dams. Lactation was prolonged out to 37 days by cross-fostering 7-day-old pups onto each dam every 7 days as previously described (Hadsell et al 2005(Hadsell et al , 2006. The relative maternal capacity for milk production was estimated using the weight gain of these independent cross-fostered litters during each of four 7-day periods, days 7-14, 14-21, 21-28, and 28-35.…”

Section: Experimental Animalsmentioning

confidence: 99%

“…This enhancement of lactation persistence has been suggested to be a valuable means of improving the well-being of dairy animals as well as enhancing profitability of dairy operations (van Amburgh et al 1997). To take advantage of the power of mouse genetics, our laboratory has developed a litter cross-fostering approach that allows for studies on lactation persistence to be conducted using mice as a model for dairy animals (Hadsell et al 2006(Hadsell et al , 2007. Following this approach, we demonstrated increased lactation persistence in a strain of transgenic mice (WAP-DES) that overexpress des(1-3)human IGF-I (hIGF-I) within the mammary gland (Hadsell et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression

Hadsell¹,

Parlow²,

Torres³

et al. 2008

Journal of Endocrinology

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GH, prolactin (PRL), and IGF-I stimulate lactation-related metabolic processes in mammary epithelial cells. However, the ability of these factors to stimulate milk production in animals varies depending on species and experimental variables. Previous work in our laboratory demonstrated that transgenic overexpression of des(1-3)IGF-I within the mammary glands of lactating mouse dams increased lactation capacity during prolonged lactation. This work also suggested that some of the effects of the overexpressed IGF-I may have been mediated through elevated concentrations of IGF-I or PRL in the systemic circulation. In the present study, murine GH and PRL, and a human IGF-I analog, long-R3-IGF-I (LR3), were administered as s.c. injections to compare their ability to enhance milk production, and alter mammary gland signaling and gene expression. Lactation capacity, as measured by litter gain, was increased (P!0 . 05) by GH, but not by PRL. LR3 increased (P!0 . 05) mammary phospho-Akt and suppressors of cytokines signaling 3 (SOCS3) gene expression, and had a modest ability to increase (P!0 . 05) lactation capacity. GH both increased (P!0 . 05) mammary SOCS1 expression and decreased (P!0 . 05) mammary expression of tryptophan hydroxylase 1, the rate-limiting enzyme in the synthesis of serotonin and a potential feedback inhibitor of lactation. These results suggest that while both GH and IGF-I stimulate milk production in the lactating mouse, the effect of GH may be additionally mediated through IGF-I-independent effects associated with repression of mammary serotonin synthesis.

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“…Our laboratory has used litter cross-fostering approaches to measure relative milk production in the mouse (27)(28)(29). These approaches have allowed for indirect measurement of milk production capacity during all stages of the cycle with a degree of increased sensitivity and precision that has not been present in previous studies.…”

mentioning

confidence: 99%

In silico QTL mapping of maternal nurturing ability with the mouse diversity panel

Hadsell

Wei

Olea

et al. 2012

Physiological Genomics

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Changes in secretory cell turnover, and mitochondrial oxidative damage in the mouse mammary gland during a single prolonged lactation cycle suggest the possibility of accelerated cellular aging

Cited by 26 publications

References 57 publications

Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle

Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle

Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression

In silico QTL mapping of maternal nurturing ability with the mouse diversity panel

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