Mammary gland proliferation in female rats: Effects of the estrous cycle, pseudo-pregnancy and age

Hvid, Henning; Thorup, Inger; Sjögren, Ingrid; Oleksiewicz, Martin B.; Jensen, Henrik Elvang

doi:10.1016/j.etp.2010.09.005

Cited by 24 publications

(32 citation statements)

References 37 publications

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“…Ki67 and Cl-Caspase 3 are routinely used for detecting cell proliferation and apoptosis respectively. Similar to earlier findings in rats [17], the percentage of Ki67 positive cells is high in virgin tree shrew mammary glands, low (<5%) in lactation and involution stages and absent at the gestation stage. Apoptotic (Cl-Caspase 3 positive) cells were only identified in tree shrew mammary glands during the involution period ( Fig.…”

Section: Normal Tree Shrew Mammary Glands At Different Mammary Gland supporting

confidence: 88%

PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews

Xia

Wang

et al. 2014

European Journal of Cancer

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Section: Normal Tree Shrew Mammary Glands At Different Mammary Gland supporting

confidence: 88%

PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews

Xia

Wang

et al. 2014

European Journal of Cancer

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“…After day 50–55 of age development of mammary gland may be partially resemble early pregnancy [ 19 , 30 ]. Fluctuations in mammary cell proliferation related to the oestrous cycle have been detected in pubertal rodents [ 26 ].With each estrous cycle, the TEB proliferate and branch, to give rise to terminal ductules and alveolar buds [ 14 ]. Hvid et al [ 14 ] observed proliferation of the mammary epithelium mainly in the terminal end buds in the young animals whereas proliferating cells in mature animals were more equally distributed in the different compartments of the mammary gland.…”

Section: Rat Mammary Gland Development and Tumorigenesismentioning

confidence: 99%

“…In Sprague Dawley rats, gradually prolonged proestrus and estrus can progress to persistent estrus, which can be followed by pseudo-pregnancy after which persistent estrus can resume before persistent anestrus occurs. Estrous cycle irregularities and associated changes in endogenous concentrations of estradiol, progestrone and prolactin are likely to have an effect on mammary gland proliferation [ 14 ].…”

Section: Rat Mammary Gland Development and Tumorigenesismentioning

confidence: 99%

Relationship between histology, development and tumorigenesis of mammary gland in female rat

et al. 2016

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The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential.

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“…Among the proliferation markers, Ki-67 is widely accepted and used for the evaluation of histological slides. A good correlation with BrdU has been proven for many species, including the rat (Muskhelishvili et al 2003) and in particular for the mammary gland (Hvid et al 2012). In addition, the in vivo injection and further shortcomings of BrdU may be avoided, and therefore, Ki-67 has been recommended as the first-choice marker in rodents (Birner et al 2001).…”

Section: Overview On Repeated Dose Toxicity Studies Evaluated In Thismentioning

confidence: 99%

Regulatory Forum Opinion Piece

et al. 2016

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The toxicological profile of insulins is exclusively due to exaggerated pharmacology resulting in hypoglycemic findings. Insulin analogues displaying modifications and aimed at improving pharmacokinetics do not induce different toxicity. The main target is the brain displaying neuronal necrosis. Wallerian degeneration of nerves occurs rarely after severe hypoglycemia. These findings are of potential human relevance; nevertheless, these changes are induced in normoglycemic animals whereas diabetic patients suffer from hyperglycemia. Therefore, it is usually not difficult to achieve a therapeutic window for subsequent use in patients. Based upon this and in the absence of classical toxicity, there has been no scientific need for diabetic animal models. A greater challenge is the mitogenicity already inherent with regular insulin. Thus, the focus for preclinical safety evaluation of analogues is to demonstrate that modifications in regular insulin do not result in enhanced mitogenicity. The approaches used to assess the mitogenic potential of insulin analogues have changed over time driven by scientific progression and changes within the regulatory environment. Therefore, in vitro and in vivo evaluation of cell proliferation has become common practice, and to date there has been no evidence that the mitogenic potential of insulin analogues may be increased compared to regular insulin.

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Mammary gland proliferation in female rats: Effects of the estrous cycle, pseudo-pregnancy and age

Cited by 24 publications

References 37 publications

PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews

PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews

Relationship between histology, development and tumorigenesis of mammary gland in female rat

Regulatory Forum Opinion Piece

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