Abstract
BackgroundIn mammalian females, reproductive capacity is determined by the size of the primordial follicle pool. During embryogenesis, oogonia divide mitotically but cytokinesis is incomplete so oogonia remain connected in germ cell cysts. Oogonia begin to enter meiosis at 13.5 days postcoitum in the mouse and over several days, oocytes progress through the stages of meiotic prophase I arresting in the diplotene stage. Concurrently, germ cell cysts break apart and individual oocytes become surrounded by granulosa cells forming primordial follicles. In rats, inhibition of a synaptonemal complex protein caused premature arrival at the diplotene stage and premature primordial follicle assembly suggesting diplotene arrest might trigger primordial follicle formation. Cyst breakdown and primordial follicle formation are blocked by exposure to steroid hormones but hormone effects on the timing of diplotene arrest are unclear. Here, we asked: (1) if oocytes were required to arrest in diplotene before follicles formed, (2) if all oocytes within a germ cell cyst arrested at diplotene synchronously, and (3) if steroid hormones affected progression through prophase I.MethodsMeiotic stage and follicle formation were assessed in histological sections. Statistical differences over time were determined using one-way ANOVA followed by Newman-Keuls multiple comparisons test. To determine if steroid hormones affect the rate of progression to the diplotene stage, 17.5 dpc ovaries were placed in organ culture with media containing estradiol, progesterone or both hormones. In this case, differences were determined using one-way ANOVA followed by Dunnett’s multiple comparisons test.ResultsWe found primordial follicles containing oocytes at the diplotene stage as well as follicles containing oocytes at pre-diplotene stages. We also found individual germ cell cysts containing oocytes at both diplotene and pre-diplotene stages. Progesterone but not estradiol reduced the number of diplotene oocytes in ovary organ culture.ConclusionsOur results suggest that meiotic progression and primordial follicle formation are independent events. In addition, oocytes in germ cell cysts do not synchronously proceed through meiosis. Finally, only progesterone delayed transit though meiotic prophase I.
Highlights
In mammalian females, reproductive capacity is determined by the size of the primordial follicle pool
Meiotic progression and diplotene arrest in developing mouse ovaries To investigate the relationship between meiotic progression and primordial follicle formation, we first performed a quantitative study on histological sections from 13.5 dpc to PND5, determining the number of oocytes at each meiotic stage
The first diplotene oocytes were observed at 17.5 dpc, when about 8% of the oocytes were at the diplotene stage (Fig. 1a)
Summary
Reproductive capacity is determined by the size of the primordial follicle pool. Oogonia begin to enter meiosis at 13.5 days postcoitum in the mouse and over several days, oocytes progress through the stages of meiotic prophase I arresting in the diplotene stage. The primordial germ cells migrate to the genital ridge and divide by mitosis until 13.5 days postcoitum (dpc) [2]. During these divisions the germ cells are known as oogonia and develop in germ cell cysts due to incomplete cytokinesis following each cell cycle [3]. During the same time period, germ cell cysts break apart and individual oocytes become surrounded by granulosa cells forming primordial follicles [6]. Some follicles, referred to as the first wave of developing follicles are activated to grow immediately after forming while most follicles are not activated until sexual maturity developing in groups in a cyclical fashion [7, 8]
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