Related Experiment Videos
Immunomodulation by diethylstilbestrol is dose and gender related: effects on thymocyte apoptosis and mitogen-induced
J B Calemine1, R M Gogal, A Lengi
1Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg 24061-0342, USA.
Abstract:
It is believed, but not proven, that the immunomodulatory effects of DES may vary with the dose and/or gender. To address these critical gaps in the literature, diethylstilbestrol (DES) was administered to female and male CD-1 mice as four subcutaneous injections for 1 week at 0, 5, 15, and 30 microg/kg bw doses, and immunological and reproductive effects examined a day after the last injection. Female thymuses were significantly larger than their male counterparts. Short-term administration of DES to female or male mice neither induced thymic atrophy nor altered the relative percentages of thymic subsets. Nevertheless, DES treatment of female or male mice induced a dose-related apoptosis of CD4(+)8(+), CD4(+)8(-) and CD4(-)8(+) subsets as analyzed by 7-amino-actinomycin D (7-AAD). Immature CD4(-)8(-) subset of thymocytes from females was also affected by high dose DES. The pattern of mitogen-induced proliferation of splenic lymphocytes varied with the dose of hormone and the gender. In females, splenic lymphocytes from low dose DES (5 microg/kg bw)-treated mice exhibited an increased proliferative response to Con-A, LPS or PMA/ionomycin compared with controls. Similar cultures from mice treated with higher doses of DES (15 or 30 microg/kg bw) did not manifest an increased proliferative response, but rather showed a trend for suppressed proliferation, especially in response to Con-A. In males, DES had minimal effects with the exception of increased proliferative response to Con-A in splenocytes from medium-dose-DES-treated mice. The changes in mitogen-induced proliferation in DES-treated female mice were not mirrored by similar changes in the relative numbers of CD90(+) or CD45R(+) cells, or in ratios of anti-apoptotic Bcl-2 to apoptotic Bax proteins. Con-A-activated splenocytes from DES-treated mice, particularly from females, had a decreased ability to secrete interferon-gamma compared with controls. Taken together, these findings suggest that short-term exposure to DES has differential immunological effects depending upon the dose of hormone and sex.
Insights
Diethylstilbestrol (DES) exposure in mice showed dose- and gender-dependent effects on the immune system. Short-term DES treatment induced thymocyte apoptosis and altered splenic lymphocyte proliferation, with varying responses in males and females.
Area of Science:
- Immunology
- Endocrinology
- Toxicology
Background:
- Diethylstilbestrol (DES) is a synthetic estrogen with known endocrine-disrupting properties.
- The immunomodulatory effects of DES are not fully understood, particularly concerning dose and gender variations.
- Gaps exist in the literature regarding short-term DES exposure and its impact on immune and reproductive systems.
Purpose of the Study:
- To investigate the dose- and gender-specific immunomodulatory effects of short-term diethylstilbestrol (DES) exposure in mice.
- To examine the impact of DES on thymocyte apoptosis and splenic lymphocyte proliferation.
- To assess changes in cytokine production following DES treatment.
Main Methods:
- CD-1 mice (female and male) received four subcutaneous injections of DES at varying doses (0, 5, 15, 30 microg/kg bw) over one week.
- Immunological assessments included thymic subset analysis, apoptosis assays (7-AAD), and mitogen-induced splenic lymphocyte proliferation.
- Flow cytometry was used to analyze thymocyte subsets and cell populations (CD90+, CD45R+).
- Interferon-gamma secretion by Con-A-activated splenocytes was measured.
Main Results:
- DES treatment induced a dose-related apoptosis in thymocyte subsets (CD4+8+, CD4+8-, CD4-8+) in both genders.
- Female thymuses were significantly larger than male thymuses, but DES did not induce thymic atrophy.
- Splenic lymphocyte proliferation varied by DES dose and gender; low-dose DES increased proliferation in females, while higher doses trended towards suppression.
- DES minimally affected male splenic lymphocytes, except for increased Con-A response at a medium dose.
- DES-treated female mice showed reduced interferon-gamma secretion from Con-A-activated splenocytes.
Conclusions:
- Short-term DES exposure exerts differential immunomodulatory effects that are dependent on both the dose administered and the sex of the animal.
- DES induces thymocyte apoptosis and alters splenic lymphocyte function in a dose- and gender-specific manner.
- The observed immunological changes suggest potential disruptions in immune responses following DES exposure.