Effects of methoxychlor (MXC) and estradiol-17beta (E) were studied in mouse preimplantation embryos. Pregnant mice received s.c. injections of sesame oil only, 10 microg E, or 0.5 mg purified (95%) MXC on Days 2-4 of pregnancy (plug = Day 1). Another group received a single dose of 2.5 microg E on Day 2 only. Based on the average weight of pregnant females, 10 microg of estradiol was equivalent to 0.33 mg/kg of bw, 2.5 microg of estradiol was equivalent to 0.082 mg/kg of bw, and the 0.5-mg dose of MXC was equivalent to 16.5 mg/kg of bw. All embryos were collected for analyses on Day 4. MXC and both estradiol-17beta doses suppressed embryonic development to blastocyst, decreased embryo cell numbers, and caused abnormal blastocyst formation. The high estradiol-17beta dose significantly increased the percent degenerating embryos and caused a tube-locking effect, with retention of embryos in the oviduct. In contrast to estradiol-17beta, MXC at the dose used in this study did not alter tubal transport of embryos. Also in contrast to estradiol-17beta, MXC increased the percentage of nuclear fragmentation and micronuclei. In preimplantation embryos, MXC and estradiol-17beta both suppressed embryo development. MXC effects were, however, different from those of estradiol-17beta, indicating a difference in mechanism of action, possibly due to cytotoxicity and induction of apoptosis.
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http://dx.doi.org/10.1016/s0890-6238(02)00095-3 | DOI Listing |
Toxicol Sci
January 2020
Division of Toxicology, Wageningen University, Stippeneng 4, Wageningen, 6708 WE, The Netherlands.
The present study assessed the potential of a generic physiologically based kinetic (PBK) model to convert in vitro data for estrogenicity to predict the in vivo uterotrophic response in rats for diethylstibestrol (DES), ethinylestradiol (EE2), genistein (GEN), coumestrol (COU), and methoxychlor (MXC). PBK models were developed using a generic approach and in vitro concentration-response data from the MCF-7 proliferation assay and the yeast estrogen screening assay were translated into in vivo dose-response data. Benchmark dose analysis was performed on the predicted data and available in vivo uterotrophic data to evaluate the model predictions.
View Article and Find Full Text PDFToxicol Appl Pharmacol
September 2018
The Institute of Environmental Toxicology, 4321, Uchimoriya-machi, Joso-shi, Ibaraki, Japan. Electronic address:
It has been reported that endogenous or exogenous estrogens can affect the immune system, resulting in immune disorders; however, their direct involvement in such conditions remains to be demonstrated. The purpose of this study was to investigate whether estrogen receptors (ER) are directly implicated in pro-pruritic and pro-inflammatory reactions in cutaneous allergy. Initially, enhancement of the pro-inflammatory response by several ER agonists [methoxychlor (MXC), β-estradiol (E2), propylpyrazoletriol (PPT; an ERα agonist), and diarylpropionitrile (DPN; an ERβ agonist)] was examined in vivo using a male BALB/c mouse model of allergic dermatitis induced by toluene-2,4-diisocyanate administration.
View Article and Find Full Text PDFTheriogenology
June 2018
Department of Endocrinology, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland. Electronic address:
The objective of the study was to examine the effects of androgen and estrogen agonists or antagonists on the follicle formation, ovarian cell proliferation and apoptosis as well as plasma steroid concentration in neonatal pigs. Piglets were injected with testosterone propionate (TP, 20 mg/kg bw), flutamide (FLU, 50 mg/kg bw), 4-tert-octylphenol (OP, 100 mg/kg bw), ICI 182,780 (ICI, 400 μg/kg bw), methoxychlor (MXC, 100 mg/kg bw) or corn oil (CTR, controls) between postnatal Days 1 and 10 (n = 4/group). Heart blood was collected and ovaries were excised from the 11-day-old piglets.
View Article and Find Full Text PDFToxicol Sci
September 2016
Department of Pediatrics and Human Development, and Institute for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824;
Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 µM for MXC and 126 µM for VIN.
View Article and Find Full Text PDFAquat Toxicol
August 2016
Department of Physiological Sciences and Center for Environmental and Human Toxicology and Genetics Institute, University of Florida, Gainesville, FL 32611 USA.
Largemouth bass (Micropterus salmoides) inhabiting Lake Apopka, Florida are exposed to high levels of persistent organochlorine pesticides (OCPs) and dietary uptake is a significant route of exposure for these apex predators. The objectives of this study were to determine the dietary effects of two organochlorine pesticides (p, p'-dichlorodiphenyldichloroethylene; p, p' DDE and methoxychlor; MXC) on the reproductive axis of largemouth bass. Reproductive bass (late vitellogenesis) were fed one of the following diets: control pellets, 125ppm p, p'-DDE, or 10ppm MXC (mg/kg) for 84days.
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