Fertility of female mice fed coumestrol and diethylstilbestrol

Elias, Elias A.; Kincaid, R.L.

doi:10.1080/03601238409372442

Cited by 8 publications

(3 citation statements)

References 12 publications

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“…Further, we have shown altered ovarian differentiation following neonatal exposure to genistein. Studies using other phytoestrogens including coumestrol [96,97], daidzein [34,72], and red clover [98,99] have also demonstrated disruptions in reproduction and/or reproductive endpoints supporting the concept that phytoestrogens, although weaker than other more potent estrogens such as DES or 17b-estradiol, can cause adverse effects on the developing reproductive tract. Some of these effects may not be apparent until later in life such as irregular estrous cyclicity, early reproductive senescence, and infertility and therefore would not be detected during the time of exposure.…”

Section: Discussionmentioning

confidence: 95%

Disruption of the developing female reproductive system by phytoestrogens: Genistein as an example

Jefferson¹,

Padilla-Banks²,

Newbold³

2007

Molecular Nutrition Food Res

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Studies in our laboratory have shown that exposure to genistein causes deleterious effects on the developing female reproductive system. Mice treated neonatally on days 1-5 by subcutaneous injection of genistein (0.5-50 mg/kg) exhibited altered ovarian differentiation leading to multioocyte follicles (MOFs) at 2 months of age. Ovarian function and estrous cyclicity were also disrupted by neonatal exposure to genistein with increasing severity observed over time. Reduced fertility was observed in mice treated with genistein (0.5, 5, or 25 mg/kg) and infertility was observed at 50 mg/kg. Mammary gland and behavioral endpoints were also affected by neonatal genistein treatment. Further, transgenerational effects were observed; female offspring obtained from breeding genistein treated females (25 mg/kg) to control males had increased MOFs. Thus, neonatal treatment with genistein at environmentally relevant doses caused adverse consequences on female development which is manifested in adulthood. Whether adverse effects occur in human infants exposed to soy-based products such as soy infant formulas is unknown but the neonatal murine model may help address some of the current uncertainties since we have shown that many effects obtained from feeding genistin, the glycosolated form of genistein found in soy formula, are similar to those obtained from injecting genistein.

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Section: Discussionmentioning

confidence: 95%

Disruption of the developing female reproductive system by phytoestrogens: Genistein as an example

Jefferson¹,

Padilla-Banks²,

Newbold³

2007

Molecular Nutrition Food Res

View full text Add to dashboard Cite

show abstract

“…Further, we have shown altered ovarian differentiation following neonatal exposure to genistein. Studies using other phytoestrogens including coumestrol [23, 80], daidzein [25, 73] and red clover [81, 82] have also demonstrated disruptions in reproduction and/or reproductive endpoints supporting the concept that phytoestrogens, although weaker than other more potent estrogens such as DES or 17β-estradiol, can cause adverse effects on the developing reproductive tract. Some of these effects may not be apparent until later in life such as irregular estrous cyclicity, early reproductive senescence and infertility and therefore would not be detected during the time of exposure.…”

Section: Discussionmentioning

confidence: 98%

Circulating levels of genistein in the neonate, apart from dose and route, predict future adverse female reproductive outcomes

Jefferson

Williams

2011

Reproductive Toxicology

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Developmental exposure to estrogenic compounds can disrupt sexual differentiation and adult reproductive function in many animals including humans. Phytoestrogens (plant estrogens) in the diet comprise a significant source of estrogenic exposure to humans, particularly in infants who are fed soy-based infant formula. Animal models have been developed to test the effects of phytoestrogen exposure on the developing fetus and neonate. Here we review studies quantifying the amount of phytoestrogen exposure in human adults and infants and discuss the few available epidemiological studies that have addressed long-term consequences of developmental phytoestrogen exposure. We then describe in detail rodent models of developmental exposure to the most prevalent phytoestrogen in soy products, genistein, and the effects of this exposure on female reproductive function. These models have used various dosing strategies to mimic the phytoestrogen levels in human populations. Serum circulating levels of genistein following each of the models and their correlation to reproductive outcomes are also discussed. Taken together, the studies clearly demonstrate that environmentally relevant doses of genistein have significant negative impacts on ovarian differentiation, estrous cyclicity, and fertility in the rodent model. Additional studies of reproductive function in human populations exposed to high levels of phytoestrogens during development are warranted.

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“…[9][10][11][12][13][14] In mice, bitches, and male dogs, use of COU has been assessed as a treatment for controlling reproduction. [15][16][17] COU is commonly diluted in dimethyl sulfoxide (DMSO) before administration. However, DMSO may independently influence reproduction in mammals, since it has been shown to modulate estrogenic responses in hepatocytes of fish, 18,19 and to induce cell differentiation of rat mammary glands.…”

Section: Introductionmentioning

confidence: 99%

Effect of a single application of coumestrol and/or dimethyl sulfoxide, on sex hormone levels and vaginal cytology of anestrus bitches

et al. 2019

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Canine overpopulation continues to be a problem with serious public health implications, despite a diversity of programs and strategies that have been implemented for its control. Coumestrol (COU) is an organic compound with estrogenic activity, thus having the potential to alter reproduction in mammals. COU is commonly dissolved in dimethyl sulfoxide (DMSO) before administration; however, evidence indicates that DMSO is not inert. The aim of this study was to assess the effects of either a single oral administration of COU diluted in DMSO or of DMSO-alone, on serum progesterone (P4) and estradiol (E2), on vaginal cell pattern, and on anestrus and diestrus lengths in bitches. Fifteen anestrus female dogs received either a single commercial dog food biscuit (Control, n=5), a biscuit with 600 μg of COU/kg diluted in 20 μL of DMSO (COU, n=5), or a biscuit with 20 μL of DMSO (DMSO, n=5). Circulating P4, E2, and changes in vaginal cytology, were assessed within the first month after treatment administration. Hormone levels were also measured from months 2-6 post-treatment. Mean differences were analyzed by the GLM procedure for repeated measures. COU enhanced serum E2 levels, and DMSO increased serum P4, number of vaginal anucleated superficial cells, and diestrus length. All dogs were deemed healthy based on all periodical clinical exams, but abnormal mammary gland growth and/or galactorrhea were observed in two COU and one DMSO-treated bitches. The findings of the present study expose the need to reevaluate previous reports of use of COU in bitches, and perhaps in other mammals.Figure 1. Progesterone (A) and estradiol (B) serum levels in anoestrous bitches receiving a commercial dog food biscuit alone (Control; n=5), a biscuit with coumestrol diluted in dimethyl sulfoxide (COU; n=5), or a biscuit with only dimethyl sulfoxide (DMSO; n=5). a,b Different letters within sampling day indicate difference between treatments (P<0.05).*specifies statistical increase on post-treatment days 21 (P<0.0048) and 28 (0.0008). Data are presented as LSM ± standard error.

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Fertility of female mice fed coumestrol and diethylstilbestrol

Cited by 8 publications

References 12 publications

Disruption of the developing female reproductive system by phytoestrogens: Genistein as an example

Disruption of the developing female reproductive system by phytoestrogens: Genistein as an example

Circulating levels of genistein in the neonate, apart from dose and route, predict future adverse female reproductive outcomes

Effect of a single application of coumestrol and/or dimethyl sulfoxide, on sex hormone levels and vaginal cytology of anestrus bitches

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