FIGURE 1.

Main developmental events of the ovary organogenesis uncovered by 3D imaging in mice. (A) Following the localization in the gonad, germ cells undergo meiosis (in magenta) asynchronously starting as early as E12.5 in the anterior-medial region of the ovary. Germ cells located in the peripheral-posterior part of the ovary maintain their pluripotency (cyan) and initiate the meiosis later and by E16.5, all germ cells enter meiosis. Formation of primary follicles (in orange) and the first activation of follicular growth occur in the anterior-dorsal region of the postnatal ovary. While the number of follicles decreases with advanced maternal age, aged ovaries harbor mostly primordial and primary follicles due to the decreased number of later stage follicles. (B) Blood vessels (in red) at the gonad-mesonephros border expand into the gonad at E11.5 and proliferate to establish the blood vessel network of the developing ovary. Although further development of the vascular network in late fetal ovaries is unclear, blood vessels in the postnatal ovaries enter from the hilum and blood vessel diameters and branching increase by adulthood. (C) Lymphatic vessels (in blue) invade the ovary as early as PN10, however, the first point of contact inside the PN10 ovary is unclear with the resolution of micrographs. Similar to blood vessels, the adult ovary contains a complex network of lymphatic vessels. (D) Nerve fibers (in green) in the mesonephros innervate the ovary first from the dorsal side at E16.5, neural projections expand to medulla then cortex by PN4 and the neural network further increases with age. Dashed lines adjacent to fetal ovaries illustrate mesonephros. Question marks in (B–D) refer unidentified geography of related structures at given developmental points in 3D.