Early exposure to genistein exerts long-lasting effects on the endocrine and immune systems in rats.
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.


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.


CONCLUSIONS
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.
Klein
Sabra L
SL
The W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. saklein@jhsph.edu
Wisniewski
Amy B
AB
Marson
Aimee L
AL
Glass
Gregory E
GE
Gearhart
John P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004032:Diet; D004703:Endocrine System / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D007107:Immune System / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007774:Lactation; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011863:Radioimmunoassay; D051381:Rats; D020318:Rats, Long-Evans; D013154:Spleen / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism*; D013950:Thymus Gland / Q000187:drug effects
D000970:Antineoplastic Agents; D015847:Interleukin-4; D013739:Testosterone; D007371:Interferon-gamma; D019833:Genistein