Phenotypic Effects of Knockout of Oocyte-Specific Genes

Abstract

Folliculogenesis is a complex process requiring both extragonadal and intragonadal factors aimed at the production of fully mature oocytes, ready to be fertilized. The follicle is the functional unit of the ovary, where the tight communication between the oocyte and the surrounding somatic cells allows controlled growth and differentiation of the oocyte to form the ovum, the female gamete that supplies the many proteins and factors necessary for fertilization events and early embryonic development. At birth, the female has a finite oocyte population. By day 2 after birth in the mouse, a layer of squamous granulosa cells surrounds the oocytes to form quiescent primordial follicles. Unknown intragonadal factors regulate the entry of primordial follicles into the growing phase. At this point the follicle is committed to a program of growth and differentiation that culminates in either apoptotic death of the granulosa cells (atresia) and oocyte or ovulation of the mature oocyte. Initiation of follicle growth is marked by a squamous to cuboidal morphological transition of the pregranulosa cells to form a one-layer primary follicle. As follicular growth progresses, granulosa cells proliferate, fibroblast-like cells from the interstitium are recruited to form the theca layer, and the oocyte grows and secretes an extracellular glycoprotein matrix, the zona pellucida. The final stages of follicular growth are marked by the appearance of scattered fluid-filled spaces between granulosa cells, which collapse into a single antral cavity. The antral follicles that become responsive to gonadotropins are selected for further development to form preovulatory follicles, in which a meiotically competent oocyte protrudes into the antral cavity, surrounded by cumulus granulosa cells. The luteinizing hormone (LH) surge triggers the release of the oocyte from meiotic arrest, breakdown of the follicle wall, and extrusion of the cumulus¡ªoocyte complex into the oviduct. The oocyte completes meiosis I and progresses to the metaphase stage of meiosis II, where it arrests again until fertilization. The granulosa cells remaining in the ovary undergo luteinization and form the corpus luteum, a transient endocrine organ that produces progesterone, essential for uterine preparation and maintenance of pregnancy.