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Hyperandrogenism Induces Histo-Architectural Changes in the Rat Uterus

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Abstract

The effects of androgens on the uterus have been poorly studied and they need to be clarified to understand why androgen excess, such as observed in women with polycystic ovary syndrome (PCOS), is a risk factor for the development of endometrial hyperplasia, cancer, and infertility. Thus, uterine histomorphology in a PCOS experimental model was evaluated. Beginning at weaning, female rats were injected daily with dehydroepiandrosterone (DHEA, 6 mg/100 g body weight) or vehicle (sesame oil) for 20 consecutive days. On postnatal day 41 (PND41), DHEA-treated animals showed high serum testosterone levels. In addition, uterine histological analysis showed a significant increase in luminal epithelial height and glandular density without changes in cell proliferation. The thickness of the subepithelial stroma and myometrium also increased in these animals. The effect of DHEA on uterine thickness was accompanied by a significant reduction in cell density in both tissue compartments (subepithelial stroma and myometrium). Cell proliferation was not altered in the myometrium, whereas a decrease in the proliferative activity was seen at PND41 in the subepithelial stroma of DHEA animals. The analysis of the extracellular space showed that the changes in the thickness of the subepithelial stroma and myometrium were related to an increase in the organization of collagen fibers and water imbibition. The latter was associated with higher aquaporin 3 and 8 expression. This study provides evidence to further the understanding of PCOS-associated hyperandrogenism effects on uterine architecture. This could have implications for the regulation of uterine function and the development of uterine lesions.

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Authors and Affiliations

  1. Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Paraje El Pozo, Casilla de Correo 242, 3000, Santa Fe, Argentina

    Gisela Soledad Bracho BS, Gabriela Anahí Altamirano PhD, Laura Kass PhD, Enrique Hugo Luque PhD & Verónica Lis Bosquiazzo PhD

  2. Cátedra de Patología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

    Gabriela Anahí Altamirano PhD & Laura Kass PhD

  3. Cátedra de Fisiología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

    Enrique Hugo Luque PhD

  4. Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

    Verónica Lis Bosquiazzo PhD

Authors
  1. Gisela Soledad Bracho BS
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  2. Gabriela Anahí Altamirano PhD
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  3. Laura Kass PhD
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  4. Enrique Hugo Luque PhD
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  5. Verónica Lis Bosquiazzo PhD
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Correspondence to Verónica Lis Bosquiazzo PhD.

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Authors’ Note

E.H.L. and V.L.B. shared last authorship.

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Bracho, G.S., Altamirano, G.A., Kass, L. et al. Hyperandrogenism Induces Histo-Architectural Changes in the Rat Uterus. Reprod. Sci. 26, 657–668 (2019). https://doi.org/10.1177/1933719118783881

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