5 - The early stages of follicular growth

Summary

Introduction

Since the first edition of Biology and Pathology of the Oocyte, the use of technologies such as transgenic mouse models and microarray analyses has significantly increased our knowledge of early stages of follicular growth. In the present chapter, we will show that activation of resting follicles as well as early follicular growth are regulated by local factors produced by ovarian cell types (oocyte, granulosa, theca, and stroma) that mediate a dialog between neighbor follicles. Although it is now widely accepted that early stages of follicular growth are minimally gonadotropin-dependent, the role of follicle-stimulating hormone (FSH) will be revisited in the light of early studies suggesting that FSH might be, either directly or indirectly, involved in these processes. Nevertheless, identification of factors governing early folliculogenesis remains difficult because of the multiplicity of signaling pathways and molecules of unknown function, as revealed by microarray analyses, whereas the exact role played by specific factors is very complex to determine because of the presence within the ovary of a mixture of arrested and developing follicles.

Aging changes

In the human ovary, primordial follicles begin to form during the fourth month of fetal life and although some of these follicles start to grow almost immediately, most of them remain in a resting stage. The stock of dormant follicles constitutes the ovarian reserve. In humans at birth, each ovary contains between 250 000 and 500 000 resting follicles (reviewed in [1]). In all mammalian species, resting follicles leave the stock in a continuous stream, either by apoptosis or by entry into the growth phase, thus depleting the ovarian reserve. Atresia of resting follicles is difficult to quantify because of the very quick disappearance of apoptotic oocytes. However, it can be estimated that apoptosis is responsible for approximately 90% of the ovarian reserve attrition. In physiological conditions, the factors triggering the onset of the apoptotic cascade in resting follicles remain unknown and, therefore, require further promising studies. The depletion rate of the ovarian reserve, which may be variable between subjects, accelerates, either continuously [2] or from approximately 38 years of age, leading to a stock at menopause estimated at less than 100 (see [1]).