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Updated: Aug 7, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Estrogen agonists, 17beta-estradiol, bisphenol A, and diethylstilbestrol, decrease cortactin expression in the mouse
Reiko Anahara1, Miyo Yoshida, Yoshiro Toyama
1Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Inohana, Japan.
Abstract:
Previous reports have revealed that estrogen agonists or anti-androgenic chemicals induce abnormal spermiogenesis in rodents. In the seminiferous epithelium, the apical ectoplasmic specialization (ES) is an actin-based (cell-cell) junctional structure developing between the Sertoli cells and spermatids as is the basal ES also--although it is located between adjoining Sertoli cells. In the apical and basal ES are several adhesion complex proteins that control the spermatid developing process. Cortactin, an actin-binding protein, is one of the ES adhesion proteins, combining with several cell-cell adhesions associating proteins. In the present study, 17beta-estradiol (E2, 1.2 microg/kg), bisphenol A (BPA, 2.4 microg/kg), and diethylstilbestrol (DES, 2.5 microg/kg) were subcutaneously injected in ICR 12-week-old male mice. Mice testes were observed for the expression of cortactin protein after E2, BPA, and DES treatments by Western blot analysis, immunohistochemical analysis, and immunoelectron microscopic analysis. Observations showed that the immunoreactivity of the treated testes was significantly decreased. The immunohistochemical reactivity of cortactin in the apical ES was decreased in the treated testis. In immunoelectron microscopic observations, ultrastructural immunolocalizations of cortactin protein in the apical ES by both E2 and BPA were decreased, and the immuno-gold particles of apical and basal ES by DES were much less than the control. In the toxicological field, cortactin may be considered to be one of the indicator proteins of abnormal spermiogenesis which is affected by exogenous chemicals, such as endocrine disrupting chemicals. In summary, this study helps toward understanding the cortactin protein expression underlying the histological abnormalities of spermatogenesis induced by exogenous hormonal chemical treatment.
Insights
Endocrine-disrupting chemicals like E2, BPA, and DES reduce cortactin protein in mouse testes, indicating abnormal spermiogenesis. This suggests cortactin is a key indicator for chemical-induced reproductive toxicity.
Area of Science:
- Reproductive Toxicology
- Cell Biology
- Endocrinology
Background:
- Estrogen agonists and anti-androgenic chemicals are known to disrupt rodent spermiogenesis.
- Ectoplasmic Specializations (ES) are crucial cell-cell junctions in the seminiferous epithelium, involving proteins like cortactin.
- Cortactin, an actin-binding protein, plays a role in ES adhesion complexes essential for spermatid development.
Purpose of the Study:
- To investigate the effect of 17beta-estradiol (E2), bisphenol A (BPA), and diethylstilbestrol (DES) on cortactin protein expression in mouse testes.
- To determine if cortactin can serve as an indicator protein for chemically induced abnormal spermiogenesis.
Main Methods:
- Subcutaneous injection of E2, BPA, and DES into male ICR mice.
- Analysis of cortactin protein expression using Western blot, immunohistochemistry, and immunoelectron microscopy.
- Assessment of cortactin localization in apical and basal ectoplasmic specializations (ES).
Main Results:
- E2, BPA, and DES treatments significantly decreased cortactin immunoreactivity in mouse testes.
- Immunohistochemical analysis showed reduced cortactin in the apical ES of treated testes.
- Immunoelectron microscopy revealed decreased ultrastructural localization of cortactin in the apical and basal ES following exposure to these chemicals.
Conclusions:
- Cortactin protein expression is significantly reduced by exposure to exogenous hormonal chemicals like E2, BPA, and DES.
- Cortactin serves as a potential indicator protein for abnormal spermiogenesis caused by endocrine-disrupting chemicals.
- This study enhances the understanding of cortactin's role in the histological abnormalities of spermatogenesis induced by hormonal chemical treatments.
