Fluctuations of Lactoferrin Protein and Messenger Ribonucleic Acid in the Reproductive Tract of the Mouse during the Estrous Cycle

Newbold, Retha R.; Teng, Christina T.; Beckman, William C.; Jefferson, Wendy N.; Hanson, Rita B.; Miller, Julia V.; McLachlan, John A.

doi:10.1095/biolreprod47.5.903

Cited by 62 publications

(36 citation statements)

References 30 publications

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“…Uterine tissues were processed and embedded in paraffin with one horn placed longitudinally and the other placed cross-wise; sections were cut at 4 µm and stained with hematoxylin and eosin (H&E). We quantitated histologic responses using an Olympus BH-2 Microscope (Olympus Corp., New Hyde Park, NY) interfaced with an image analysis system (Southern Micro Instruments, Atlanta, GA) as described previously (22,27).…”

Section: Methodsmentioning

confidence: 99%

“…Because of our experience with the CD-1 mouse and our previously published data on the uterotropic responses in this strain (14)(15)(16)(17)(18), we compared uterine responses in this mouse strain with responses in the Sprague-Dawley rat. We investigated the sensitivity of both species to varying doses of 17β-estradiol by comparing uterine wet weight increase and a number of morphologic and biochemical end points that are known estrogenic responses in both species (19)(20)(21)(22)(23)(24). Because developing tissues are particularly susceptible to perturbation by hormones (25,26), we restricted our study to the use of immature rather than adult ovariectomized animals.…”

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confidence: 99%

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The immature mouse is a suitable model for detection of estrogenicity in the uterotropic bioassay.

Padilla-Banks

Jefferson

Newbold

2001

Environ Health Perspect

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The traditional rodent uterotropic response assay has been incorporated into the U.S. Environmental Protection Agency's screening and testing program for environmental endocrine-disrupting chemicals (EDCs). While much effort continues to focus on determining protocol variables, few studies compare uterotropic responses in rats, a species commonly used in toxicologic testing, with other rodent species. In this study, we compared uterine responses in immature outbred CD-1 mice and Sprague-Dawley rats. After three daily subcutaneous injections with 17beta-estradiol (0.1-500 microg/kg/day), immature mice and rats demonstrated a similar dose-response increase in absolute uterine wet weight and uterine weight:body weight ratio. Further, morphologic and biochemical parameters of estrogenicity, including uterine epithelial cell height and number, gland number, and induction of estrogen-responsive proteins lactoferrin and complement C3, mirror wet weight increases. We conclude that mice are as well suited as rats for the uterotropic bioassay. Because of the advantages of using mice, including lower costs, less space required, and smaller amounts of compound needed for tests, mice should be given appropriate consideration in testing paradigms for EDCs.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

The immature mouse is a suitable model for detection of estrogenicity in the uterotropic bioassay.

Padilla-Banks

Jefferson

Newbold

2001

Environ Health Perspect

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“…Tables 1 and 2 (25) and 0.01 pglkg/day for the neonatal mouse uterus (20,21,23 (50,51). The expression of lactoferrin is induced by DES in the uterus prenatally, neonatally, and in adult stages (52), thus making it a particularly attractive biomarker of DES action in the mouse. Lactoferrin has also been localized to a subset of epithelial cells of the human endometrium and is responsive to estrogen (53 induced teratogenicity and/or carcinogenicity should be explored.…”

Section: Animal Models Summary Ofthe Modelsmentioning

confidence: 99%

New approaches for estimating risk from exposure to diethylstilbestrol.

Cunha

Forsberg

Golden

et al. 1999

Environ Health Perspect

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A subgroup from a National Institute of Environmental Health Sciences, workshop concerned with characterizing the effects of endocrine disruptors on human health at environmental exposure levels considered the question, If diethylstilbestrol (DES) were introduced into the market for human use today and likely to result in low-dose exposure of the human fetus, what would be required to assess risk? On the basis of an analysis of the quality of data on human DES exposure, the critical times and doses for inducing genital tract malformations and cancer must be determined. This would be facilitated through analysis of the ontogeny of estrogen receptor expression in the developing human genital tract. Models of low-dose estrogenic effects will have to be developed for human and rodent genital tract development. Mouse models offer many advantages over other potential animal models because of the wealth of the earlier literature, the availability of sensitive end points, the availability of mutant lines, and the possibility of generating genetically engineered model systems. Through multidisciplinary approaches, it should be possible to elucidate the cellular and molecular mechanisms of endocrine disruption elicited by estrogens during development and facilitate an assessment of risk to humans. (4,5) and were thought to cross the placenta in humans (6,7), direct evidence of teratogenicity of estrogens in humans was unknown until after the association between DES and vaginal adenocarcinoma was reported. In any case, despite the tragedy of the DES episode, the human DES clinical data offer an unprecedented opportunity to learn about the consequences of in utero exposure to a potent estrogen and thus to infer potential risks following exposure to less potent environmental estrogens.If properly interpreted, lessons from the DES episode may prove invaluable for judging potential effects of compounds that have been or will be identified as potential endocrine disruptors. It will be important, however, to keep in mind the considerable differences in potency between such compounds when inferences are drawn concerning potential effects. For example, the carcinogenicity of DES was identified in a human study including only 8 cases and 32 controls (8). Normal sample size calculations would rule such a study as inadequate. However, because the cancer induced by DES (clear cell vaginal adenocarcinoma) was so rare in young women, the association between prenatal DES exposure and development of clear cell adenocarcinoma of the vagina was easily identified. Clearly, most chemicals with significantly less potent endocrine (e.g., estrogenic) effects will convey much-reduced risks, particularly at low doses. Thus, study designs for other endocrine disruptors will have to be more precise and more powerful, especially if the background incidence of a particular lesion is substantial. Given the history of the DES episode, we have considered this issue: If DES were introduced into the market for human use today and were likely to result in ...

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“…At diestrus, lactoferrin protein levels were very low in uterine epithelial cells and absent in uterine luminal fluid, whereas at proestrus, lactoferrin mRNA and protein levels increased in uterine luminal fluid and uterine epithelium and reached their highest levels at estrus. At early metestrus lactoferrin levels decreased, and by late metestrus, lactoferrin decreased to an extremely low level (210,211). The promoter region of the lactoferrin gene has been shown to contain an estrogen response element 349 base pairs (bp) upstream of the transcription start site (212).…”

Section: Altered Steroid Hormone Homeostasis In Fishmentioning

confidence: 99%

Chronic Toxicity of Environmental Contaminants: Sentinels and Biomarkers

LeBlanc¹,

Bain²

1997

Environmental Health Perspectives

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Due to the use of a limited number of species and subchronic exposures, current ecological hazard assessment processes can underestimate the chronic toxicity of environmental contaminants resulting in adverse responses of sentinel species. Several incidences where sentinel species have responded to the effects of chronic exposure to ambient levels of environmental contaminants are discussed, including the development of neoplasia in fish, immunosuppression in marine mammals, pseudohermaphrodism in invertebrates, teratogenicity in amphibians, and aberrations in the sexual development of fish and reptiles. Biomarkers of chronic toxicity, including DNA mutations, alterations in specific protein and mRNA levels, and perturbations in metabolism, are presented. The incorporation of appropriate surrogate species and biomarkers of chronic toxicity into standard toxicity characterizations is proposed as a means of significantly refining the ecological hazard assessment process. -Environ Health Perspect 105(Suppl 1): 65-80 (1997)

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Fluctuations of Lactoferrin Protein and Messenger Ribonucleic Acid in the Reproductive Tract of the Mouse during the Estrous Cycle

Cited by 62 publications

References 30 publications

The immature mouse is a suitable model for detection of estrogenicity in the uterotropic bioassay.

The immature mouse is a suitable model for detection of estrogenicity in the uterotropic bioassay.

New approaches for estimating risk from exposure to diethylstilbestrol.

Chronic Toxicity of Environmental Contaminants: Sentinels and Biomarkers

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