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Science Forum Index » Life Extension Forum » Lifetime effects of infant exposure to genistein
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| kofi |
 Posted: Mon Jan 12, 2004 4:06 am |
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Mol Med. 2002 Nov;8(11):742-9. Related Articles, Links
Early exposure to genistein exerts long-lasting effects on the
endocrine and immune systems in rats.
Klein SL, Wisniewski AB, Marson AL, Glass GE, Gearhart JP.
The W. Harry Feinstone Department of Molecular Microbiology and
Immunology, The Johns Hopkins Bloomberg School of Public Health,
Baltimore, Maryland 21205, USA.
BACKGROUND: Although the immunologic effects of endogenous and
synthetic estrogens are well studied, few studies have examined the
hormonal effects of phytoestrogens (i.e., plant-derived estrogens) on
the immune system. The primary goal of this study was to compare the
effects of perinatal exposure with life-long exposure to genistein, an
estrogenic compound in soy, on the endocrine and immune system in
adulthood. MATERIALS AND METHODS: Pregnant female rats were exposed to
no, low (5 mg/kg diet), or high (300 mg/kg diet) genistein diets
throughout gestation and lactation. At weaning, male offspring exposed
to genistein perinatally were either switched to the genistein-free diet
or remained on the genistein-dosed diets. At 70 days of age, immune
organ masses, lymphocyte subpopulations, cytokine concentrations, and
testosterone concentrations were assessed in male offspring. RESULTS:
Data were analyzed based on the diets that males were exposed to during
gestation and lactation because life-long exposure to genistein had no
additional effect on any of the dependent measures. Relative thymus
masses were greater among males exposed to the high genistein diet than
among males exposed to no genistein. Although the proportions of splenic
and thymic CD4+ T cells were not altered by genistein, the percentages
of CD4+CD8+ thymocytes, CD8+ splenocytes, and total T cells in the
spleen were higher and the percentages of CD4-CD8- thymocytes were lower
among males exposed to genistein than among males not exposed to
genistein. Synthesis of interferon-gamma (IFN-gamma) was marginally
higher and testosterone concentrations were lower among
genistein-exposed than genistein-free males. DISCUSSION: These data
illustrate that exposure to genistein during pregnancy and lactation
exerts long-lasting effects on the endocrine and immune systems in
adulthood. Whether exposure to phytoestrogens during early development
affects responses to infectious or autoimmune diseases, as well as
cancers, later in life requires investigation.
PMID: 12520091 [PubMed - indexed for MEDLINE]
J Urol. 2003 Apr;169(4):1582-6. Related Articles, Links
Click here to read
Exposure to genistein during gestation and lactation demasculinizes
the reproductive system in rats.
Wisniewski AB, Klein SL, Lakshmanan Y, Gearhart JP.
Division of Pediatric Endocrinology, Department of Pediatrics, The
Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
PURPOSE: Exposure to the phytoestrogen genistein (Indofine Chemical
Co., Somerville, New Jersey) can disrupt normal male sexual
differentiation. To determine if perinatal (that is gestation and
lactation) genistein exposure at doses common in human diets alters
masculinization we examined the development of the external genitalia,
testes, wolffian ducts and sexual behavior in male rats exposed to
genistein supplemented diets during early development. MATERIALS AND
METHODS: Female rats were fed a phytoestrogen-free diet supplemented
with no genistein (free), a low genistein dose (low) or a high genistein
dose (high) throughout gestation and lactation. Anogenital distance of
male offspring was measured weekly from postnatal days 2 to 21. At
puberty (postnatal day 40 to 45) preputial separation, and testis length
and width of male offspring were measured. At age 70 days reproductive
organ masses, plasma testosterone concentration, sperm counts and sexual
behavior were assessed in male offspring.RESULTS Exposure to genistein
resulted in temporary, prepubertal urogenital abnormalities at postnatal
days 21 and 40. Males exposed to genistein had smaller anogenital
distance and testis size, and delayed preputial separation. Perinatal
exposure to genistein also caused long-term dysfunction in reproductive
behavior, in which adult males exposed to genistein were less likely to
mount, intromit and ejaculate during mating tests. Males exposed to
genistein also had lower testosterone concentrations in adulthood.
CONCLUSIONS: Perinatal genistein exposure results in transient and
lasting alterations in masculinization of the reproductive system. These
results extend our knowledge of the effects of early genistein exposure
on male development and may have implications for human health in terms
of potential relationships of endocrine disrupters and urogenital
abnormalities thought to be increasing in incidence in boys and men.
PMID: 12629420 [PubMed - indexed for MEDLINE]
J Nutr. 2003 Jul;133(7):2287-93. Related Articles, Links
Click here to read
Dietary diethylstilbestrol but not genistein adversely affects rat
testicular development.
Fritz WA, Cotroneo MS, Wang J, Eltoum IE, Lamartiniere CA.
Department of Pharmacology and Toxicology, University of Alabama at
Birmingham, Birmingham, AL 35294, USA.
Isoflavones, including genistein, contribute to the health benefits
of a soy diet. However, the estrogenic activity of genistein suggests
that there may be adverse effects on reproductive tract development. We
investigated the potential of exposure to genistein (250 and 1000 mg/kg
diet) and the synthetic estrogen and known male reproductive toxicant,
diethylstilbestrol (DES, 75 micro g/kg diet) from d 21 to d 35 to alter
rat testicular development. These dietary genistein concentrations
resulted in serum concentrations that approximate or exceed
concentrations in Asian men on a soy-containing diet. DES exposure
reduced testicular weights, altered morphology and increased apoptosis
in the seminiferous tubules. The effects of DES were accompanied by a
reduction in androgen receptor (AR) protein concentrations,
predominantly localized to Sertoli cells. Increased expression and
immunostaining for the epidermal growth factor receptor (EGFR) and its
downstream extracellular signal-regulated kinases (ERK) 1 and 2 in
spermatagonia and spermatocytes were also observed. Immunohistochemical
analysis of serial sections demonstrated that greater EGFR expression
correlated with increased cellular proliferation, rather than apoptosis,
and reflected impaired testicular development in DES-treated rats.
Genistein in the diet did not significantly alter testicular weights,
morphology, AR, EGFR and ERK expression or apoptosis. However, the
higher concentration significantly reduced testicular aromatase
activity, an effect that may contribute to reduced estrogen
concentrations and suppression of prostate cancer development. These
data suggest that exposure to genistein in the diet at concentrations
that result in serum concentrations at the upper limit of humans
consuming soy products does not adversely affect testicular development,
but may provide health benefits.
PMID: 12840195 [PubMed - indexed for MEDLINE] |
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