Oogonium

An oogonium (plural: oogonia) is a small, diploid cell. In a female fetus, it matures into a primordial follicle; in certain thallophytes, it serves as the female gametangium, which may be haploid or diploid. In mammalian fetuses, oogonia arise early in development when primordial germ cells undergo extensive mitosis. In humans, this process begins between the fourth and eighth weeks, and oogonia are present in the fetus from the fifth through the thirtieth week.

In human ovaries, normal oogonia are spherical or ovoid. They sit among neighboring somatic cells and oocytes at various developmental stages. Under an electron microscope, oogonia are distinguishable from somatic cells by their nuclei: oogonial nuclei contain scattered fibrillar and granular material, while somatic nuclei are more condensed and appear darker. Oogonial nuclei also feature prominent, dense nucleoli. When an oogonium is dividing mitotically, its chromosomal material appears as a dense mass surrounded by vesicles or double membranes. The cytoplasm of oogonia resembles that of nearby somatic cells, with large, round mitochondria that have lateral cristae. However, the endoplasmic reticulum (E.R.) is notably underdeveloped, consisting of many small vesicles; some of these vesicles contain ribosome-studded cisternae and sit near the Golgi apparatus. Degenerating oogonia look different: their chromosomes clump into an indistinct mass, and their mitochondria and E.R. appear swollen and disrupted. Such cells are often found partially or fully engulfed by neighboring somatic cells, indicating they are removed by phagocytosis.

In the mammalian embryo, primordial germ cells originate from the proximal epiblast of the blastocyst, guided by extra-embryonic signals. These cells travel by amoeboid movement to the genital ridge and then into the undifferentiated gonads. Around the fourth or fifth week, the gonads begin to differentiate; without a Y chromosome, they become ovaries. As the ovaries form, ingrowths called cortical cords develop, and primordial germ cells gather there. Between the sixth and eighth weeks of female (XX) embryonic development, these germ cells grow and start differentiating into oogonia. Oogonia then proliferate by mitosis from the ninth through the twenty-second week. By the eighth week, there can be up to 600,000 oogonia; by the fifth month, up to 7,000,000. Eventually, each oogonium either degenerates or undergoes asymmetric division—a mitotic process where one oogonium divides unequally, producing one daughter cell that will become an oocyte via oogenesis and another that remains an identical oogonium. This asymmetric division occurs from the fifteenth week to the seventh month. By birth, most oogonia have either degenerated or turned into primary oocytes. Primary oocytes then enter meiosis but are arrested in prophase I until puberty. This contrasts with male primordial germ cells, which are arrested as spermatogonia at birth and do not begin meiosis until puberty.

The regulation of germ cell differentiation into primary gametocytes depends on the embryo’s sex and gonad differentiation. In female mice, the protein RSPO1 drives ovary differentiation by activating the β-catenin signaling pathway through up-regulation of Wnt4. Ovaries lacking Rspo1 or Wnt4 can undergo sex reversal, forming ovotestes and somatic Sertoli cells (which normally aid sperm development). After female germ cells collect in the undifferentiated gonads, up-regulation of Stra8 is required for them to become oogonia and eventually enter meiosis. A key trigger for Stra8 up-regulation is the β-catenin pathway initiated by RSPO1, which is produced in somatic cells and acts on germ cells in a paracrine manner. However, RSPO1 is not the only factor involved; other regulators are still under investigation.

It has long been thought that oogonia either degenerate or differentiate into primary oocytes, which then arrest in prophase I after birth. This would mean adult female mammals lack a renewable germ cell population, relying instead on a fixed pool of primary oocytes that dwindles with each menstrual cycle until menopause. However, recent research suggests that renewable oogonia may exist in the ovarian lining of humans, primates, and mice, potentially playing a role in maintaining the oocyte supply.