The origin and evolution of lactation

The presence of mammary glands is the defining morphological feature of mammals. The recent assembly of the bovine genome and a report in Genome Biology that links the milk and lactation data of bovine and other mammalian genomes will help biologists investigate this economically and medically important feature

In vitro expansion of the mammary stem/progenitor cell population by xanthosine treatment

Mammary stem cells are critical for growth and maintenance of the mammary gland and therefore are of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo, and hepatic and hair follicle stem cells in vitro. In the latter, xanthosine promoted the symmetrical division of hepatic and hair follicle stem cells. The objective of this study was to determine if treating primary cultures of bovine mammary epithelial cells (MEC) with xanthosine increases the stem/progenitor cell population by promoting symmetrical division of mammary stem cells. In vitro treatment with xanthosine increased the population of MEC during the exponential phase of cell growth, reducing the doubling time from 86 h in control cultures to 60 h in xanthosine-treated cultures. The bromodeoxyuridine (BrdU) labeling index and the proportion of MEC in S-phase both were increased by xanthosine treatment, indicating that increased cell accretion was due to increased cell proliferation. Analysis of daughter-pairs indicated that xanthosine promoted a shift from asymmetric to symmetric cell division. Moreover, the 30 % increase in symmetric cell division was concomitant with an increase in the proportion of MEC that were positive for a putative stem cell marker (FNDC3B) and a trend toward increased telomerase activity. These results suggest that xanthosine treatment in vitro can increase cell proliferation, promote symmetric cell division and enhance stem/progenitor cell activity. Xanthosine treatment increased the proliferation rate of bovine MEC in vitro. This was likely to be mediated by an increase in the proportion of stem/progenitor cells in the MEC population due to promotion of symmetrical stem cell division by xanthosine.https://doi.org/10.1186/1471-2121-13-1

Adrenomedullin (AM) and adrenomedullin binding protein (AM-BP) in the bovine mammary gland and milk: Effects of stage of lactation and experimental intramammary \u3ci\u3eE. coli\u3c/i\u3e infection

Adrenomedullin (AM) has been characterized as an endogenous tissue survival factor and modulator of many inflammatory processes. Because of the increased susceptibility of the mammary gland to infection during the time surrounding parturition in the cow, we investigated how milk and tissue content of AM and its binding protein (AM-BP) might be affected by the stage of lactation and the udder health status. Milk and mammary biopsy samples were obtained from Holstein cows 21 days prior to and at various times after calving to represent the dry period and early and midstages of lactation. Additional cows received an intramammary challenge with Escherichia coli for immunohistochemical characterization of AM and AM-BP. Milk AM concentrations were relatively constant across the stages of lactation while AM-BP increased two-fold (P \u3c 0.04) between early and mid-lactation. Milk AM (P \u3c 0.04) and AM-BP (P \u3c 0.03) increased as somatic cell counts (SCCs) increased within a given stage of lactation. Tissue content of both (AM and AM-BP) were significantly affected by stage of lactation, lowest in the dry period and progressively increasing to peak at mid-lactation as well as increasing in association with higher levels of SCCs. Following E. coli challenge, AM increased in epithelial cells surrounding mammary alveoli presenting high levels of SCCs. The data suggest that AM and AM-BP are cooperatively regulated in the mammary gland during lactation; changes in localized tissue AM and AM-BP content reflect a dynamic regulation of these tissue factors in the bovine mammary gland consistent with their protective effects within inflamed tissue

In vivo expansion of the mammary stem/progenitor cell population by xanthosine infusion

Mammary stem cells provide for growth and maintenance of the mammary gland and are therefore of considerable interest as determinants of productivity and efficiency of dairy animals and as targets of carcinogenesis in humans. Xanthosine treatment was previously shown to promote expansion of hepatic stem cells in vitro. The objective of this study was to determine if in vivo treatment with xanthosine can increase the mammary stem cell population. Xanthosine was infused into the right mammary glands of four female Holstein calves for 5 consecutive days. Immediately after each xanthosine treatment, calves were injected intravenously with 5-bromo-2-deoxyuridine (BrdU). Forty days after the final treatment, calves were euthanized and mammary tissue harvested. BrdU-label retaining epithelial cells (LREC) were detected immunohistochemically and quantified. Retention of BrdU was used as a marker for putative bovine mammary stem cells. Infusion of xanthosine into the bovine mammary gland significantly increased the number of LREC in treated glands compared to contralateral control glands (P < 0.05). LREC averaged 0.4% of epithelial cells in control glands and 0.8% in xanthosine-treated glands. The increase in LREC in xanthosine-treated glands was supported by a concomitant increase in telomerase activity (P < 0.01) and a correlation between LREC and telomerase (P < 0.05; r2= 0.7). Data indicate that in vivo treatment with xanthosine can be used to increase the number of mammary stem cells. This is the first demonstration of an in vivo treatment to increase the endogenous population of mammary stem cells, with utility for biomedical research and dairy management. Copyright © 2009 by the Society for Experimental Biology and Medicine