Development of the Ovary and Early Follicular Growth
**Introduction**
The ovary plays a pivotal role in the maturation of oocytes and the secretion of hormones, such as estrogen, progesterone, inhibins A and B, and relaxin, which impact various target tissues, including the breast, bone, uterus, hypothalamus, and pituitary. This intricate process involves dynamic changes within the ovary, making it one of the most dynamically changing organs in the body. This article explores the stages of ovarian development and early follicular growth.
**Embryonic Development**
Primordial germ cells emerge as early as the third week of gestation, completing their migration to the genital ridge by the sixth week. These germ cells, initially referred to as oogonia, are crucial for initiating ovarian development. In cases of 45,X Turner syndrome, primordial germ cells proliferate and migrate to the genital ridge but cannot persist, as their survival depends on the presence of pregranulosa cells, contingent upon both X chromosomes.
**Population Dynamics**
The germ cell population expands, with oogonia entering prophase of the first meiotic division and transitioning into primary oocytes around the eighth week of gestation. This transition allows the formation of primordial follicles, where each oocyte is surrounded by a single layer of flattened granulosa cells. Granulosa cells, originating from early mesonephric cells that infiltrate the ovary, push the germ cells towards the periphery.
Mitosis, meiosis, and atresia processes drive the oogonia population to its peak of 6-7 million by the 20th week of gestation. Afterward, there's a gradual loss of both oogonia and primordial follicles through atresia, with entry into meiosis providing some protection against programmed cell death. At birth, oogonia are absent, leaving only 1-2 million germ cells in the form of primordial follicles.
The oocyte remains in prophase of the first meiotic division until just before ovulation, when meiosis resumes. Quiescent primordial follicles are recruited for further growth and differentiation in a regulated process that ensures folliculogenesis continues throughout reproductive life.
**Maturation and Communication**
The initial recruitment of primordial follicles leads to the formation of primary follicles. At this stage, granulosa cells develop receptors for follicle-stimulating hormone (FSH), estradiol, and androgens, establishing communication via gap junctions.
Bidirectional signaling between germ cells and somatic cells is essential for oocyte maturation and hormone secretion. Various factors, such as GDF-9, BMP-15, KIT ligand, and FOXL2, influence these processes, and genetic mutations can lead to premature ovarian insufficiency.
**Development of a Mature Follicle**
Early follicle growth is primarily influenced by intraovarian factors. Development to the secondary follicle stage can take nearly a year. Further maturation to the preovulatory stage, involving the resumption of meiosis in the oocyte, requires the combined stimulus of FSH and LH.
Secondary follicles are recruited from the resting follicle pool under the influence of FSH, while anti-müllerian hormone (AMH) from small growing follicles restrains FSH, controlling the number of follicles entering active growth.
Granulosa cells divide into mural and cumulus cells as follicular fluid accumulates, leading to the formation of an antrum. Differential exposure to growth factors and vascular endothelial growth factor (VEGF) influences the selection of a dominant follicle for continued growth.
The dominant follicle undergoes rapid expansion before ovulation, marked by granulosa cell proliferation, FSH receptor abundance, and elevated estradiol and inhibin A levels. Ovulation, triggered by the LH surge, requires the production of extracellular matrix, cumulus cell expansion, and the expulsion of the egg and follicular fluid, aided by progesterone, prostaglandins, and matrix metalloproteinases.
**Conclusion**
Ovarian development and follicular growth involve intricate processes orchestrated by a multitude of factors, ensuring the production of mature oocytes and the secretion of essential hormones for reproductive and physiological functions.