Diabetes mellitus (DM) affects the ovary by reducing the number and diameters of ovarian follicles and increasing atretic follicles. Follicular growth and diameters depend on VEGF production. Hyperglycemia causes ovarian stromal and follicular degeneration then fibrosis by activating TGF-β. Insulin and metformin promote development of ovarian follicles and reduce atretic follicles. Therefore, the present study investigates the ovarian VEGF and TGF-β immune-expression and its variations in diabetic, insulin and metformin-treated rats. Forty adult female albino rats were divided equally into four groups: control, diabetic (STZ-induced diabetes), diabetic metformin-treated group (100 mg/kg/day orally/eight weeks) and diabetic insulin-treated group (5 U insulin /day). Ovarian sections were stained with hematoxylin and eosin, Masson’s trichrome, immunohistochemistry for VEGF and TGF-β. The diabetic group showed noticeable atrophic and degenerative changes in cortex and medulla as well as increased density and distribution of the collagenous fibers. The number and diameter of primary, secondary and tertiary follicles were decreased. However, the number of atretic follicles and corpus luteum was increased. Significant decrease in the surface area percentage of VEGF immuno-expression and significant increase in TGF-β immuno-expression surface area percentage were detected. By treating animals with metformin and insulin, there was restoration of the ovarian histological structure more or less as in control. DM negatively affects the histological and morphometric parameters of ovaries. Furthermore, insulin showed more beneficial effects than metformin in hindering these complications by modifying the expression of VEGF and TGF-β.

中文翻译：

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二甲双胍和胰岛素治疗后，糖尿病大鼠卵巢组织形态，VEGF和TGF-β的免疫表达发生变化，并可能改善。

糖尿病（DM）通过减少卵巢卵泡的数量和直径并增加闭锁卵泡来影响卵巢。滤泡的生长和直径取决于VEGF的产生。高血糖会引起卵巢基质和滤泡变性，然后通过激活TGF-β引起纤维化。胰岛素和二甲双胍促进卵巢卵泡发育并减少闭锁卵泡。因此，本研究调查了在糖尿病，胰岛素和二甲双胍治疗的大鼠中卵巢VEGF和TGF-β的免疫表达及其变化。将40只成年雌性白化病大鼠平均分为四组：对照组，糖尿病（STZ诱导的糖尿病），糖尿病二甲双胍治疗组（100 mg / kg /天，口服/八周）和糖尿病胰岛素治疗组（5 U胰岛素/天）。卵巢切片用苏木精和伊红（Masson's trichrome）染色，VEGF和TGF-β的免疫组织化学。糖尿病组在皮质和髓质中显示出明显的萎缩和退行性改变，以及胶原纤维的密度和分布增加。初级，次级和三级卵泡的数量和直径减少。然而，无定形卵泡和黄体的数量增加了。检测到VEGF免疫表达的表面积百分比显着降低和TGF-β免疫表达的表面积百分比显着增加。通过用二甲双胍和胰岛素治疗动物，与对照组相比，或多或少地恢复了卵巢组织学结构。DM对卵巢的组织学和形态学参数产生负面影响。此外，