scholarly journals Establishment and characterization of mammary organoids from non-traditional model organisms

2021 ◽  
Author(s):  
Arianna P. Bartlett ◽  
Gerlinde R. Van de Walle
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Mammary Gland Development ◽  
Model Organisms ◽  
Mammary Tissue ◽  
Traditional Model ◽  
Mammary Gland Tissue ◽  
3D Matrix ◽  
And Function ◽  
Gland Development

ABSTRACTMammary organoid (MaO) models are only available for a few traditional model organisms, limiting our ability to investigate mammary gland development and cancer across the diverse taxa of mammals. For example, horses are mammals with a similar mammary anatomy and function as humans, but they have a remarkably low incidence of mammary cancer, making the development of MaOs in non-traditional model organisms attractive, particularly in comparative cancer research. This study established equine mammary organoids (EqMaOs) from mammary gland tissue fragments and evaluated parameters including diameter, budding, and growth stage in non-budding EqMaOs, in cultures with increasing concentrations of epidermal growth factor (EGF), a key growth factor implicated in mammary gland development. Our findings showed that EqMaO diameter is not influenced by EGF concentration, whereas number of EqMaOs with budding and stage in non-budding EqMaOs are positively influenced by increasing EGF concentration. EqMaOs also formed protrusions with putative functions, including organoid fusion and sensory functions. We further characterized EqMaOs by the presence of myoepithelial and luminal cells using immunohistochemistry and used the hormone prolactin to stimulate milk secretion, as illustrated by β-lactoglobulin expression, in these EqMaOs. Additionally, we showed that our method to establish MaOs is widely applicable to additional non-traditional mammalian model organisms such as cat, pig, deer, rabbit, and prairie vole. Collectively, MaO models across species will be a useful tool for comparative developmental and cancer studies.Summary statementMammary organoids can be established from various mammals by embedding mammary tissue fragments into a 3D matrix, providing a high-throughput, physiologically accurate model for comparative studies centered on mammary gland development and cancer.

DEMONSTRATION OF MAMMOTROPHIC ACTIVITY OF THE MOUSE PLACENTA IN ORGAN CULTURE AND BY TRANSPLANTATION

1970 ◽  
Vol 48 (1) ◽  
pp. 99-107 ◽  
Author(s):  
K. KOHMOTO ◽  
H. A. BERN
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Synthetic Medium ◽  
Mammary Tissue ◽  
Mouse Placenta ◽  
Ovine Prolactin ◽  
And Function ◽  
Gland Development ◽  
Lobuloalveolar Development ◽  
Fat Pads

SUMMARY Mammotrophic (i.e. mammogenic and/or lactogenic) activity of mouse placentae of different stages (4–19 days of pregnancy) was examined using organ co-culture of placental explants with mammary tissue. The test mammary tissues were taken from midpregnant (11–12 days) nulliparous A/Crgl mice and cultured in a synthetic medium (Waymouth's) supplemented with insulin (5 μg/ml) and aldosterone (1 μg/ml). The responses of mammary gland to placental explants were judged histologically, and were compared with those seen after the addition of ovine prolactin (5 μg/ml). With placentae from 6- to 19-day pregnant animals, distinct mammotrophic activity was seen, with the appearance of eosinophilic secretion in the mammary alveolar lumina, whereas with 4- or 5-day-old 'placentae', no mammotrophic activity was detected. Inasmuch as growth hormone does not substitute for prolactin in mammary gland development and function in the A/Crgl mouse, it can be concluded that a prolactin-like factor is present in the mouse placenta. The influence of placentae on mammary gland was further analysed by transplantation of placental fragments to mammary fat pads. Local lobuloalveolar development was prominent in some instances in the area around the placental transplants.

scholarly journals Mammary Gland Specific Knockdown of the Physiological Surge in Cx26 during Lactation Retains Normal Mammary Gland Development and Function

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e101546 ◽  
Author(s):  
Michael K. G. Stewart ◽  
Isabelle Plante ◽  
John F. Bechberger ◽  
Christian C. Naus ◽  
Dale W. Laird
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Normal Mammary Gland ◽  
And Function ◽  
Gland Development

scholarly journals A Functional Connection between pRB and Transforming Growth Factor β in Growth Inhibition and Mammary Gland Development

2009 ◽  
Vol 29 (16) ◽  
pp. 4455-4466 ◽  
Author(s):  
Sarah M. Francis ◽  
Jacqueline Bergsied ◽  
Christian E. Isaac ◽  
Courtney H. Coschi ◽  
Alison L. Martens ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Growth Inhibition ◽  
Mammary Gland Development ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Mammary Development ◽  
Functional Connection ◽  
Gland Development

ABSTRACT Transforming growth factor β (TGF-β) is a crucial mediator of breast development, and loss of TGF-β-induced growth arrest is a hallmark of breast cancer. TGF-β has been shown to inhibit cyclin-dependent kinase (CDK) activity, which leads to the accumulation of hypophosphorylated pRB. However, unlike other components of TGF-β cytostatic signaling, pRB is thought to be dispensable for mammary development. Using gene-targeted mice carrying subtle missense changes in pRB (Rb1 ΔL and Rb1NF ), we have discovered that pRB plays a critical role in mammary gland development. In particular, Rb1 mutant female mice have hyperplastic mammary epithelium and defects in nursing due to insensitivity to TGF-β growth inhibition. In contrast with previous studies that highlighted the inhibition of cyclin/CDK activity by TGF-β signaling, our experiments revealed that active transcriptional repression of E2F target genes by pRB downstream of CDKs is also a key component of TGF-β cytostatic signaling. Taken together, our work demonstrates a unique functional connection between pRB and TGF-β in growth control and mammary gland development.

Lack of effect of epidermal growth factor treatment in late-pregnant ewes on subsequent lactation

1991 ◽  
Vol 58 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Christine B. Gow ◽  
Debbi J. Singleton ◽  
Mervyn J. Silvapulle ◽  
G. Philip M. Moore
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mammary Gland Development ◽  
Epidermal Growth Factor Treatment ◽  
Epidermal Growth ◽  
And Function ◽  
And Control ◽  
Gland Development ◽  
Mean Concentration ◽  
Growth Factor Treatment

SummaryTwin-bearing ewes were treated with epidermal growth factor (EGF) to determine its effect on mammogenesis and resultant milk production and composition. The EGF was infused intravenously at a dose rate of O5 mg/d in 300 ml saline between days 117 and 139 of gestation; control animals received placebo infusions of saline. All animals then received continuous infusions of 300 ml/d saline on days 139–144. Following parturition 1–5 d later, ewes were milked by hand for 10 d and thereafter were machine-milked until day 16 of lactation. At this level of treatment, EGF was not detected in the circulation during infusion and feed intake was not affected. All ewes gave birth to healthy twin lambs. There were no effects of EGF on birth weights of lambs, live weights of ewes or lengths of gestation. An EGF immunoreactive material was detected in the mammary secretions of control ewes at a mean concentration of 2 μg/l on day 1 of lactation. Two ewes had detectable levels on day 2, but none was found in the milk thereafter. In the EGF-infused group, concentrations of EGF in colostrum were ñ 10 times higher than in the control ewes on day 1 of lactation and EGF was detected in mammary secretions on day 2 but not in subsequent milk samples. A range of 0·3–0·5% of the EGF infused appeared in mammary secretions over the first 2 d of lactation. No other differences were observed for colostrum composition, subsequent milk yield or composition between the two groups of ewes indicating that mammary gland development and function were unaffected. The levels of EGF observed in the mammary secretions of treated and control ewes indicate that the mammary glands accumulate and store EGF in the pre partum period.

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