Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 28 P290

SFEBES2012 Poster Presentations Reproduction (23 abstracts)

Uterine cell turnover in a mouse model of adenomyosis caused by congenital adrenal hyperplasia

Maryam Sadraie 2 , Julie Hastings 2 , Linda Mullins 1 , John Mullins 1 , Steven Morley 2 & Christopher Kenyon 1


1Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; 2Centre for Reproductive Biology, University of Edinburgh, Edinburgh, United Kingdom.


We have investigated cell proliferation and apoptosis in Cyp11b1 null (ko) mice. Reduced glucocorticoid (corticosterone) synthesis in ko mice is associated with increased progesterone and deoxycorticosterone and the development of adenomyosis. Numbers of putative uterine stem cells were assessed in wild type (wt) and ko at an age (10–12 months) when the onset of adenomyosis was considered imminent. Mice were infused with bromodeoxyuridine (BrdU) for seven days then killed 6 weeks later. BrdU label-retaining cells (LRC) were identified by immunohistochemistry. Ki67 positive nuclei, a marker of active cell proliferation, were also visualised. Feulgen staining indicated apoptosis and Trichrome staining showed collagen deposition. In a separate cohort of animals, uterine Cyp11b1 mRNA expression was determined by in situ hybridisation. LRC in wt uteri reflected the high turnover of cells expected in a tissue responsive to oestrus cycle hormones: BrdU positive cells in stroma >lumen and gland epithelia >myometrium. Apoptotic cells were identified in all compartments of wt uteri and a distinct band of collagen was seen at the endometrial-myometrial interface. Cyp11b1 mRNA expression was not observed. Uteri of ko mice showed varying degrees of adenomyosis from hypertrophy to extensive numbers of large cysts. In contrast to wt uteri, ko had many more LRC especially within the endometrial epithelium and stroma. Compartmental differences in numbers of Ki67 positive cells within ko and wt uteri were observed, while numbers of apoptotic cells were similar. Collagen staining in ko tissue was more diffuse than wt with no defined endometrium-myometrium junction. We conclude that adenomysosis develops in cyp11b1 null mice (which do not show cyclical changes in hormones) as a result of an imbalance in rates of cell proliferation and apoptosis. Whether this is due to reduced circulating glucocorticoid hormone or sustained high levels of progesterone requires further investigation.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: Medical Research Council (G0500026).

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