What are ovarian follicles in women?

From the Guidelines

Follicles in women are small fluid-filled sacs found in the ovaries that each contain an immature egg (oocyte), with the most recent and highest quality study suggesting that an excessive number (≥20) of 2–9 mm follicles per ovary is a key criterion for defining polycystic ovarian morphology (PCOM) 1. These structures are essential to female reproduction and hormone production. During each menstrual cycle, several follicles begin to develop under the influence of follicle-stimulating hormone (FSH), but typically only one becomes dominant and releases a mature egg during ovulation. Follicles progress through several developmental stages, from primordial follicles present at birth to primary, secondary, and eventually graafian (or antral) follicles. As they grow, follicles produce estrogen, which helps prepare the uterine lining for potential pregnancy. After ovulation, the ruptured follicle transforms into the corpus luteum, which secretes progesterone. The number and quality of follicles decrease with age, which is why fertility declines as women approach menopause. Some key points to consider when evaluating follicles in women include:

• The definition of PCOM, which is a key feature of polycystic ovary syndrome (PCOS), a leading cause of anovulatory infertility 1
• The use of ultrasonographic criteria, such as the number of follicles per ovary, to diagnose PCOS 1
• The importance of standardizing methodology and technology used to assess and define PCOM 1
• The potential for alternative approaches, such as offline analysis or 3D follicle counting, to improve standardization and reproducibility 1
• The need for further research to evaluate the diagnostic accuracy of ultrasonographic ovarian markers in a large population of women with PCOS across the age and adiposity spectrum 1

From the Research

Follicles in Women

• The follicle is the functional unit of the ovary, composed of three types of cells: oocytes, granulosa cells, and theca cells 2.
• Follicles have both epithelial and stromal layers in which cell migration or movement, cell division, specialization and differentiation, and death occur 3.
• A fluid-filled antrum develops and at ovulation the epithelial cells undergo an epithelial to mesenchymal transition into luteal cells 3.

Structure and Development

• The extracellular matrix participates in all processes of follicular development, including growth factors and hormones 3.
• The follicular basal lamina changes in its composition from containing all six alpha chains of collagen type IV to only alpha 1 and alpha 2 when follicles commence growing 3.
• Perlecan and nidogen 1 subsequently become components of the follicular basal lamina, and there is an increase in the amount of laminin chains alpha 1, beta 2 and gamma 1 3.

Signaling Pathways

• Ovarian follicle development and the subsequent ovulation process are coordinated by highly complex interplay between endocrine, paracrine, and autocrine signals 2.
• Steroid hormones and their receptors play pivotal roles in follicle development and participate in a series of classical signaling pathways, such as the WNT, insulin, Notch, and Hedgehog pathways 2.
• These signaling pathways interact with FOXO3, a transcription factor that is widely known to be under control of the PI3K/AKT signaling pathway and has been implicated as a major signaling pathway in the regulation of dormancy and initial follicular activation in the ovary 2.

Clinical Relevance

• Polycystic ovary syndrome (PCOS) is one of the most common causes of ovulatory infertility, characterized by a high level of male hormones (androgens) and frequent anovulatory cycles associated with multiple ovarian microcysts 4, 5.
• Clomiphene citrate is often used as a first-line treatment for ovulation induction in anovulatory patients with PCOS, and has been shown to be effective in improving pregnancy rates 4, 5.
• However, the use of clomiphene citrate in obese women with PCOS undergoing ovarian stimulation for in vitro fertilization may be associated with impaired outcomes, including fewer oocytes retrieved and top-quality embryos 6.