coumestrol and Infertility

Topics: Animals; Chemical Phenomena; Chemistry; Coumestrol; Estrogens; Female; Infertility; Male; Plants; Poaceae; Reproduction

Phytoestrogens exist in plants that are present in forages fed to horses. They may compete with 17-β estradiol and influence the estrous cycle. Therefore, the objective was to determine whether coumestrol from clover-mixed pastures is present in mare's plasma after their ingestion (experiment I), and when this phytoestrogen was present in mare's plasma after ingestion (experiment II). The effect of a long-term ingestion of phytoestrogens on estrous cycle disruption was assessed (experiment III; clinical case). Experiment I was carried out in nonpregnant anestrous and cyclic Lusitano mares (n = 14) kept on clover and grass-mixed pastures, and supplemented with concentrate and hay or cereal straw. Blood and feedstuff were obtained from November to March. In experiment II, stabled cyclic Lusitano mares (n = 6) were fed for 14 days with increasing amounts of alfalfa pellets (250 g to 1 kg/day). Sequential blood samples were obtained for 8 hours after feed intake on Day 0 (control) and on Days 13 and 14 (1 kg/day alfalfa pellets). Experiment III mares were fed with a mixture of alfalfa and clover haylage for 5 months (group 1; n = 4) or for 9 months (group 2; n = 12). Estrous cycle was determined on the basis of plasma estradiol (E2), progesterone (P4), and ultrasound (experiment III). Concentrations of phytoestrogen coumestrol and its metabolite methoxycoumestrol were determined by high-performance liquid chromatography coupled with mass spectrometry. Phytoestrogens decreased in pasture from November until March (P < 0.01) (experiment I), but were always detected in mares' plasma. In experiment II, plasma-conjugated forms of coumestrol and methoxycoumestrol were higher on Days 13 and 14 than in control (P < 0.05). The highest concentrations of conjugated form of coumestrol were at 1.5 and 4 hours (P < 0.001), whereas its free forms peaked at 1 and at 3.5 hours after ingestion (P < 0.05). Methoxycoumestrol-conjugated form concentration was the highest at 1.5 and 5 hours (P < 0.001), whereas its free form peaked at 1 hour (P < 0.05) and at 1.5 hours (P < 0.001). Long-term intake of coumestrol caused lack of ovulation, uterine edema, and uterine fluid accumulation (experiment III). Coumestrol and methoxycoumestrol in both forms were higher in group 2 (while still ingesting haylage) than in group 1, after haylage withdrawal (P < 0.001). These data show that in the mare, coumestrol and its metabolite increase in blood after ingestion of estrogenic plants and can i

Topics: Animal Feed; Animals; Coumestrol; Eating; Endocrine Disruptors; Estrous Cycle; Female; Horses; Infertility; Ovulation; Phytoestrogens; Plants

More than 40 plant species have been shown to contain substances that are active in biological assays for estrogenic activity. Such substances may be constitutive metabolic products of a plant, or be formed adaptively in response to environmental factors, such as fungal attack (e.g. coumestrol synthesis in alfalfa infected with Pseudopeziza medicagensis); in other instances estrogens may arise from microbial attack on plant material during storage (e.g. zearalenone formation from corn by Fusarium spp.) Phyto-estrogens may reach man through direct consumption of fresh fruit, vegetables and processed plant products (e.g. administration of olive or cornoil can induce vaginal keratinization in post-menopausal women); or---more relevant to this Symposium---by consumption of carcasses and products from animals fed estrogen-containing forage. Important pasture and forage plants shown to contain phyto-oestrogens include Trifolium subterraneum L, notably the cultivars Dwalganup, Mt. Barker, Yarloop and Marrar, T. pratense (red clover), T. fragiferum L. (strawberry clover), T. alexandrinum (berseem clover), Medicago sativa (alfalfa or lucerne) and Soya hispida (soya beans). A beneficial anabolic action of the estrogens contained in these plants has been implied, but not unequivically established. More attention has been paid to their noxious effects on livestock. On affected T. subterraneum pasture, castrated male sheep showed lactation, squamous metaplasia of the bulbo-urethral glands and urethral stenosis; infertility, variously attributed to suppression of gonadotrophin release and ovulation; faulty ovum transport; premature regression of corpora lutea; irreversible cystic hyperplasia of endometrial glands on prolonged exposure; dystocia and prolapse of the uterus. Sporadic incidence of phyto-estrogen induced infertility in cattle has been reported, attended by ovarian cyst formation. Estrogenic activity in forage plants has been reported from Australia, New Zealand, India, Sweden, Great Britain, Germany, Denmark, Holland, Finland, Egypt and Israel. The clover constituents chiefly incriminated for these effects are glycosides of the isoflavone derivatives genistein and its 4'-methyl ether biochanin-A, daidzein and its 4'-methyl ether formononetin, and pratensein; coumestrol and its 3'- and 4'-methyl ethers account for the estrogenic activity of alfalfa. The isoflavone content of subterranean clover may reach 3 percent of its dry weight, and the coumestrol conten

Topics: Animals; Coumestrol; Estrogens, Non-Steroidal; Female; Infertility; Isoflavones; Male; Plants; Rats; Sheep; Sheep Diseases