In Vitro Ovarian Follicle Development

In vitro ovarian follicle development encompasses the isolation, culture and maturation of ovarian follicles outside the body, with the ultimate aim of generating developmentally competent oocytes. This process mimics in vivo folliculogenesis through sequential stages that range from primordial or secondary follicles to antral follicles and finally to metaphase II oocytes. Advances in biomaterials, microfluidics and defined culture media have enabled three-dimensional scaffolds and matrix-free systems that preserve the spatial relationship between the oocyte and its somatic cell niche. Such platforms support key biochemical and mechanical cues, encourage steroidogenesis by granulosa and thecal cells and permit controlled exposure to growth factors. Progress in this field addresses critical needs in fertility preservation for cancer patients, reproductive toxicology screening and fundamental studies of gametogenesis. Despite considerable success in rodent models, challenges remain in scaling systems for human primordial follicles, optimising long-term culture and ensuring genetic and epigenetic integrity of matured oocytes.

Research from Nature Portfolio

Recent studies have demonstrated a two-step human follicle culture strategy that successfully supports growth from the preantral to the antral stage and yields meiotically competent metaphase II oocytes. By first culturing small multi-laminar follicles in defined serum-free medium and then transferring larger follicles into an activin-supplemented environment, researchers were able to recapitulate key gonadotrophin-dependent transitions. This approach produced the first in vitro human oocytes capable of completing meiosis, highlighting the feasibility of reconstructing complete folliculogenesis in vitro with direct implications for fertility preservation and assisted reproduction.

In Vitro Ovarian Follicle Development publication trend

The graph below shows the total number of articles in in vitro ovarian follicle development across all publications each year (not limited to Nature Index journals).

Technical terms

Folliculogenesis: The process of growth and maturation of ovarian follicles from primordial to preovulatory stages.

Antral follicle: A late-stage follicle characterised by a fluid-filled cavity (antrum) and enhanced gonadotrophin dependence.

Metaphase II (MII): The meiotic stage at which the oocyte resumes and arrests, indicating full cytoplasmic and nuclear maturation.

Three-dimensional culture: A scaffold-based or scaffold-free system that maintains the spatial architecture of follicle-oocyte complexes.

Neurotrophin-4 (NT4): A growth factor that promotes follicle cell proliferation, steroidogenesis and oocyte maturation in vitro.

Mesenchymal stem cells (MSCs): Multipotent stromal cells that can support follicle survival and differentiation within engineered ovarian constructs.

References

1. Three-dimensional in vitro follicle growth: overview of culture models, biomaterials, design parameters and future directions. Reproductive Biology and Endocrinology (2010).
2. Revolutionizing the female reproductive system research using microfluidic chip platform. Journal of Nanobiotechnology (2023).
3. Human Follicle in vitro Culture Including Activation, Growth, and Maturation: A Review of Research Progress. Frontiers in Endocrinology (2020).
4. Use of ovary culture techniques in reproductive toxicology. Reproductive Toxicology (2014).
5. Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. Molecular Human Reproduction (2018).
6. Neurotrophin-4 promotes in vitro development and maturation of human secondary follicles yielding metaphase II oocytes and successful blastocyst formation. Human Reproduction Open (2024).
7. Mesenchymal stem cells promote ovarian reconstruction in mice. Stem Cell Research & Therapy (2024).
8. In vitro oogenesis from murine premeiotic germ cells using a new three-dimensional culture system. Cell Death Discovery (2023).