1 Instituto de Salud y Ambiente del Litoral (ISAL UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
2 Cátedra de Patología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
Reprod Sci. 2019 May;26(5):657-668. doi: 10.1177/1933719118783881. Epub 2018 Jun 21.
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.
雄激素对子宫的影响研究甚少，需要进一步阐明，以了解为什么雄激素过多，如多囊卵巢综合征（PCOS）患者中观察到的那样，是子宫内膜增生、癌症和不孕的危险因素。因此，评估了 PCOS 实验模型中的子宫组织形态学。从断奶开始，雌性大鼠每天接受脱氢表雄酮（DHEA，6 mg/100 g 体重）或载体（芝麻油）连续 20 天注射。在产后第 41 天（PND41），DHEA 处理的动物表现出高血清睾酮水平。此外，子宫组织学分析显示，腔上皮高度和腺体密度显著增加，而细胞增殖没有变化。这些动物的子上皮基质和子宫肌层的厚度也增加了。DHEA 对子宫厚度的影响伴随着两个组织区室（子上皮基质和子宫肌层）的细胞密度显著降低。细胞增殖在子宫肌层没有改变，而在 DHEA 动物的子上皮基质中，在 PND41 时观察到增殖活性降低。细胞外空间分析表明，子上皮基质和子宫肌层厚度的变化与胶原纤维组织和水分吸收的增加有关。后者与水通道蛋白 3 和 8 的表达增加有关。这项研究为进一步了解 PCOS 相关高雄激素血症对子宫结构的影响提供了证据。这可能对子宫功能的调节和子宫病变的发展有影响。
