Phytoestrogens & Birth Defects
There's plenty yet that you
didn't know about soy!
We at Soyonlineservice knew in
1993 that women who had been fed soy formulas in the 1970's were
infertile, miscarrying, or producing babies with defects such
as spina bifida, deformed legs and missing organs.
The risks of exposure to the quantities
of estrogens in products being consumed by pregnant women, and
by infants, that were analysed by scientists consulted by Soyonlineservice
were obvious and were specifically drawn to the attention of the
US Food and Drug Administration, US EPA, the Australian National
Food Authority, the Australian CSIRO, ANZFA, the NZ Ministry of
Health, Health Canada, UK MAFF, UK Dept of Health , WHO and FAO/Codex.
ANZFA has even secretly assessed
that soy estrogens pose health hazards to foetal and neonatal
development, to sexual maturation, and to sexual differentiation
(i.e. the ambiguity of sexual organs recited by the American Endocrine
Society
http://www.emedicine.com/ped/topic1881.htm : See page 4 re
soy and ambiguous genitalia], and by the London Independent
http://www.independent.co.uk/story.jsp?story=275758.
All of those "Food Safety"
agencies have failed to exercise the "Precautionary Principle"
of notifying women who innocently shop at supermarkets for soy
foods and infant formulas . Women do so without receiving the
slightest Government hint that there may be danger lurking for
their babies.
A real worry is that birth defects
like hypospadias
and cryptorchidism are external and visible in boys. Congenital
abnormalities of the male genital tract are also increasing, and
once again soy phytoestrogens may be implicated, according to
a study that found a higher incidence of birth
defects in male offspring of vegetarian, soy-consuming mothers.
In girls the DES effects were internal
and only showed up at adulthood (see our section on Phytoestrogens
> Soy and DES). The Wingspread
Statement also discusses birth defects from DES etc.
A discussion on the Wingspread Statement
can be found here.
One should wonder at the "dark
power" of an industry that can have such global powers to
suppress the basic legal rights of consumers everywhere.
Further Reading
Endocrine disruptors and hypospadias: role of genistein and the fungicide vinclozolin.
Vilela ML, Willingham E, Buckley J, Liu BC, Agras K, Shiroyanagi Y, Baskin LS., Urology. 2007 Sep;70(3):618-21.
These findings support the idea that exposure to genistein during gestation could contribute to the development of hypospadias.
Full
Abstract Here
Lactational transfer of the
soy isoflavone, genistein, in Sprague-Dawley rats consuming dietary
genistein.
Doerge DR, Twaddle NC, Churchwell
MI, Newbold RR, Delclos KB.
Division of Biochemical Toxicology,
National Center for Toxicological Research, U.S. Food and Drug
Administration, Jefferson, AR 72079, USA.
Exposures of Sprague-Dawley rats
to the soy isoflavone, genistein, throughout the entire lifespan
have produced a number of effects on reproductive tissues, immune
function, neuroendocrine function and behavior. Our previous studies
investigated pharmacokinetics and disposition of genistein during
adult and fetal periods and this study describes the internal
exposures of post-natal day 10 (PND10) rat pups due to lactational
transfer of genistein. Conjugated and aglycone forms of genistein
were measured by using LC/MS/MS in serum (PND10) and milk (PND7)
from lactating dams consuming a genistein-fortified soy-free diet,
and in serum from their pups at a time when milk was the only
food source (PND10). This study shows that limited lactational
transfer of genistein to rat pups occurs and that internal exposures
to the active aglycone form of genistein are generally lower than
those measured previously in the fetal period. These results suggest
that developmental effects attributable to genistein exposure
in our chronic and multi-generation studies are more likely to
result from fetal exposures because of the higher levels of the
active estrogenic aglycone form of genistein in utero, although
the possibility of neonatal responses cannot be excluded.
Detection of phytoestrogens
in samples of second trimester human amniotic fluid.
Foster WG, Chan S, Platt L, Hughes
CL Jr. Toxicol Lett 2002 Mar 28;129(3):199-205
Dietary phytoestrogens were quantified
in 96.2% of second trimester amniotic fluid samples tested. The
mean (+/- standard deviation (S.D.)) concentration of daidzein
and genistein in amniotic fluid was 1.44 +/- 1.34 and 1.69 +/-
1.48 ng/ml with maximum levels of 5.52 and 6.54 ng/ml, respectively.
Second trimester amniotic fluid contains quantifiable levels of
dietary phytoestrogens and thus is a marker of mid pregnancy fetal
exposure.
Full
Abstract Here
Neonatal exposure to genistein
induces estrogen receptor (ER)alpha expression and multioocyte
follicles in the maturing mouse ovary: evidence for ERbeta-mediated
and nonestrogenic actions.
Jefferson WN, Couse JF, Padilla-Banks
E, Korach KS, Newbold RR. Biol Reprod. 2002 Oct;67(4):1285-96.
As a functional analysis, genistein-treated
mice were superovulated and the number of oocytes was counted.
A statistically significant increase in the number of ovulated
oocytes was observed with the lowest dose, whereas a decrease
was observed with the two higher doses.
Histological evaluations on Day
19 revealed a dose-related increase in multioocyte follicles (MOFs)
in genistein-treated mice.
These data taken together demonstrate
alterations in the ovary following neonatal exposure to genistein.
Given that human infants are exposed to high levels of genistein
in soy-based foods, this study indicates that the effects of such
exposure on the developing reproductive tract warrant further
investigation.
Full
Abstract Here
The effect of phytoestrogens
on the female genital tract.
Burton JL, Wells M. J Clin Pathol
2002 Jun;55(6):401-7
This review will discuss the evidence
from both animal studies and humans for an effect of these ubiquitous
compounds on the development of the human female genital tract,
in addition to prolonging the menstrual cycle, alleviating symptoms
of the menopause, and protecting against the development of endometrial
carcinoma.
Full
Abstract Here
Placental transfer of the soy isoflavone
genistein following dietary and gavage administration to Sprague
Dawley rats.
Doerge DR, Churchwell MI, Chang
HC, Newbold RR, Delclos KB. Reprod Toxicol 2001 Mar-Apr;15(2):105-10
Fetal brain contained predominately
genistein aglycone at levels similar to those in the maternal
brain. These studies show that genistein aglycone crosses the
rat placenta and can reach fetal brain from maternal serum genistein
levels that are relevant to those observed in humans.
Full
Abstract Here
Maternal
exposure to genistein during pregnancy increases carcinogen-induced
mammary tumorigenesis in female rat offspring.
Hilakivi-Clarke L, Cho E, Onojafe I, Raygada M, Clarke
R. Oncol Rep 1999 Sep-Oct;6(5):1089-95
The results indicate that in utero
exposure to genistein, but not to zearalenone, dose-dependently
increased the incidence of DMBA-induced mammary tumors, when compared
with the controls.
Our results suggest that a maternal
exposure to subcutaneous administration of genistein can increase
mammary tumorigenesis in the offspring, mimicking the effects
of in utero estrogenic exposures. Further, increased ER protein
levels and reduced PKC activity in the mammary gland may be involved
in increasing susceptibility to carcinogen-induced mammary tumorigenesis
in rats exposed to genistein in utero.
Full
Abstract Here
p53, mutations, and apoptosis
in genistein-exposed human lymphoblastoid cells.
Morris SM, Chen JJ, Domon OE, McGarrity
LJ, Bishop ME, Manjanatha MG, Casciano DA.Mutat Res 1998 Aug 31;405(1):41-56
Our results may be interpreted
that genistein is a chromosomal mutagen
Full
Abstract Here
Neurobehavioral actions of
coumestrol and related isoflavonoids in rodents.
Whitten PL, Patisaul HB, Young
LJ. Neurotoxicol Teratol 2002 Jan-Feb;24(1):47-54
Treatment of rat dams with a 100-ppm
coumestrol diet from birth to postnatal day (PND) 21 induced premature
anovulation in female offspring, and treatment from birth to PND
10 suppressed sexual behavior in male offspring.
Full
Abstract Here
Cross-species
and interassay comparisons of phytoestrogen action.
Whitten PL, Patisaul HB. Environ Health Perspect 2001 Mar;109
Suppl 1:5-20
In vivo data show that phytoestrogens
have a wide range of biologic effects at doses and plasma concentrations
seen with normal human diets. Significant in vivoresponses have
been observed in animal and human tests for bone, breast, ovary,
pituitary, vasculature, prostate, and serum lipids. The doses
reported to be biologically active in humans (0.4--10 mg/kg body
weight/day) are lower than the doses generally reported to be
active in rodents (10--100 mg/kg body weight/day), although some
studies have reported rodent responses at lower doses.
Full
Abstract Here
Effects of dietary genistein
exposure during development on male and female CD (Sprague-Dawley)
rats.
Delclos KB, Bucci TJ, Lomax LG,
Latendresse JR, Warbritton A, Weis CC, Newbold RR. Reprod Toxicol
2001 Nov;15(6):647-63
Human exposure to genistein is
predominantly through consumption of soy products, including soy-based
infant formula and dietary supplements.
Body weight and feed consumption
of the treated dams prior to parturition showed a decreasing trend
with a significant reduction at the highest dose. Litter birth
weight was depressed in the 1250 ppm dose group, and pups of both
sexes in that dose group had significantly decreased body weights
relative to controls at the time of sacrifice. The most pronounced
organ weight effects in the pups were decreased ventral prostate
weight in males at the 1250 ppm dose and a trend toward higher
pituitary gland to body weight ratios in both sexes. Histopathologic
examination of female pups revealed ductal/alveolar hyperplasia
of the mammary glands at 250 to 1250 ppm. Ductal/alveolar hyperplasia
and hypertrophy also occurred in males, with significant effects
seen at 25 ppm and above. Abnormal cellular maturation in the
vagina was observed at 625 and 1250 ppm, and abnormal ovarian
antral follicles were observed at 1250 ppm. In males, aberrant
or delayed spermatogenesis in the seminiferous tubules relative
to controls was observed at 1250 ppm. There was a deficit of sperm
in the epididymis at 625 and 1250 ppm relative to controls, although
testicular spermatid head counts and epididymal spermatozoa counts
did not show significant differences from controls at these doses.
Both sexes showed an increase in the incidence and/or severity
of renal tubal mineralization at doses of 250 ppm and above.
Dietary genistein thus produced
effects in multiple estrogen-sensitive tissues in males and females
that are generally consistent with its estrogenic activity. These
effects occurred within exposure ranges achievable in humans.
Full
Abstract Here
Oxidative metabolism
and genotoxic potential of major isoflavone phytoestrogens.
Kulling S, Lehmann L, Metzler M.J
Chromatogr B Analyt Technol Biomed Life Sci 2002 Sep 25;777(1-2):211
Hydroxylated metabolites of daidzein
and genistein have also been demonstrated in incubations with
human hepatic microsomes and in the urine of humans after ingestion
of soy food.
Thus, oxidative metabolism appears
to be common among isoflavones and may have implications for their
biological activities.
As genistein but not daidzein exhibits
clastogenic activity in cultured mammalian cells, the role of
oxidative metabolism for the genotoxicity of isoflavones is of
particular interest.
Full
Abstract Here
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