Morphological evaluation of microvascular networks and angiogenic factors in the selective growth of oocytes and follicles in the ovaries of mouse fetuses and newborns

In the mammalian ovary, there is a striking difference in the distribution of blood vessels to individual follicles, suggesting that a microvascular network affects the selective growth of oocytes and follicles. In the present study the role of microvascular networks and angiogenic factors on the selective growth of oocytes and follicles was evaluated histologically in fetuses and newborns of ICR strain mice. Apparent selective growth of oocytes and follicles was observed in the ovaries of 1 day old newborns and, at this time, microvascular networks were recognized electronmicroscopically around the follicle that had completed the formation of its follicular structure and contained oocytes more than about 20 μm in diameter. In 3 day old newborns, oocytes more than 30 μm in diameter were detected where blood capillaries were well vascularized. Immunoreactivity to epidermal growth factor (EGF) and a strongly negative charged (colloidal iron-positive) substance (glycosaminoglycans; GAG), which have angiogenic activity, were detected in the ovaries of 3 day or older newborns and were identified more often around growing follicles containing oocytes more than 30 (GAG) and 40 (EGF) μm in diameter. Ovaries removed from 20 day old fetuses and cultured for 4 and 6 days in vitro showed a different distribution of growing follicles. A proportion of oocytes 20.0-24.9 μm in diameter increased during 4 and 6 days of incubation. However, the majority of oocytes did not grow further. These findings indicate that microvascular networks and angiogenic factors are deeply involved in selective oocyte growth beyond approximately 20-30 μm in diameter in mouse ovaries.