Oogenesis

Lore & Background

Oogenesis consists of several sub-processes: oocytogenesis, ootidogenesis, and finally maturation to form an egg cell. Folliculogenesis is a separate sub-process that accompanies and supports all three oogenetic sub-processes. The creation of oogonia traditionally does not belong to oogenesis proper but to the common process of gametogenesis. Oogonia enter meiosis during embryonic development, becoming oocytes, and meiosis begins with DNA replication and meiotic crossing over, then stops in early prophase. Mammalian oocytes are maintained in meiotic prophase arrest for a very long time—months in mice, years in humans. Initially, the arrest is due to lack of sufficient cell cycle proteins. As the oocyte grows, meiotic arrest becomes dependent on cyclic AMP, generated by adenylyl cyclase in the oocyte membrane, kept active by a constitutively active G protein-coupled receptor known as GPR3 and a G protein, Gs. Maintenance of meiotic arrest also depends on the presence of a multilayered complex of cells, known as a follicle, that surrounds the oocyte. Granulosa cells produce cyclic GMP, which diffuses into the oocyte through gap junctions and prevents the breakdown of cyclic AMP.

As follicles grow, they acquire receptors for luteinizing hormone, a pituitary hormone that reinitiates meiosis in the oocyte and causes ovulation. Luteinizing hormone acts on receptors in the outer layers of granulosa cells, causing a decrease in cyclic GMP in the granulosa cells and oocyte, allowing meiosis to resume. Meiosis then proceeds to second metaphase, where it pauses again until fertilization. In humans, oogenesis begins in embryonic development with the transformation of oogonia into primary oocytes. Primary oocytes reach their maximum development at ~20 weeks of gestational age, when approximately seven million primary oocytes have been created. At birth, this number has already been reduced to approximately 1-2 million.

Reader's Guide

Oogenesis is a fundamental biological process that underpins female fertility and reproduction in humans and other mammals. Its significance lies in the precise regulation of meiotic arrest and reinitiation, which ensures that eggs are only released at the appropriate time for fertilization. The process involves a complex interplay of hormonal signals, particularly luteinizing hormone, and cellular communication via gap junctions between granulosa cells and the oocyte. The maintenance of meiotic arrest through cyclic AMP and cyclic GMP is critical for the long-term viability of oocytes, which can remain arrested for decades in humans. The ovarian cycle, including folliculogenesis, ovulation, and corpus luteum formation, is tightly coordinated with oogenesis. Oocyte meiosis is unique among animal cell divisions as it occurs completely without the aid of spindle-coordinating centrosomes. Understanding oogenesis has implications for reproductive medicine, including treatments for infertility and insights into developmental biology.

Did You Know?

• Oocyte meiosis occurs completely without the aid of spindle-coordinating centrosomes, unlike all other instances of animal cell division.
• Primary oocytes reach their maximum development at approximately 20 weeks of gestational age, when about seven million primary oocytes have been created.
• Mammalian oocytes are maintained in meiotic prophase arrest for a very long time—months in mice, years in humans.