collection-human-follicular-fluid-follicle-somatic-cells-immature

Collection of Human Follicular Fluid, Follicle Somatic Cells, and Immature Oocytes from Individuals Undergoing<em> In Vitro </em>Fertilization

Human ovary follicular contents, including follicular fluid (FF), oocytes, cumulus cells, and somatic cells, offer a powerful yet underutilized ...

Northwestern University

Reproductive aging is associated with ovulatory defects. Age-related ovarian fibrosis partially contributes to this phenotype as short-term treatment with anti-fibrotic compounds improves ovulation in reproductively old mice. However, age-dependent changes that are intrinsic to the follicle may also be relevant. In this study, we used a mouse model to demonstrate that reproductive aging is associated with impaired cumulus expansion which is accompanied by altered morphokinetic behavior of cumulus cells as assessed by time-lapse microscopy. The extracellular matrix integrity of expanded cumulus-oocyte complexes is compromised with advanced age as evidenced by increased penetration of fluorescent nanoparticles in a particle exclusion assay and larger open spaces on scanning electron microscopy. Reduced hyaluronan (HA) levels, decreased expression of genes encoding HA-associated proteins (e.g., Ptx3 and Tnfaip6), and increased expression of inflammatory genes and matrix metalloproteinases underlie this loss of matrix integrity. Importantly, HA levels are decreased with age in follicular fluid of women, indicative of conserved reproductive aging mechanisms. These findings provide novel mechanistic insights into how defects in cumulus expansion contribute to age-related infertility and may serve as a target to extend reproductive longevity.

Cumulus expansion is impaired with advanced reproductive age due to loss of matrix integrity and reduced hyaluronan.

Are the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of reproductively adult oocyte donors?

The oocyte microenvironment is altered in adolescents compared to oocyte donors.

To investigate follicular fluid (FF) phthalate levels in adolescents undergoing fertility preservation compared to oocyte donors and explore its association with ovarian reserve and cumulus cell gene expression.

Phthalates are detected in the follicular fluid of adolescents and oocyte donors with associated changes in the cumulus cell transcriptome.

Do the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of oocyte donors?

To investigate the follicular fluid (FF) phthalate levels in adolescents undergoing fertility preservation compared with oocyte donors and explore its association with ovarian reserve and cumulus cell (CC) gene expression.

Climate change is driving significant environmental changes with profound implications for human health, including fertility. While the detrimental effects of heat on spermatogenesis are well-documented, the impact of elevated temperatures on ovaries and female fertility remains less explored. This review systematically examines the literature on heat stress (HS) effects on mammalian ovaries, follicles, and oocytes. Evidence from mammalian models indicates that HS significantly impairs ovarian function, disrupting hormone profiles, reducing ovarian size and weight, altering histology, decreasing granulosa cell viability, and compromising oocyte quality. Efforts to develop strategies and substances to mitigate these adverse effects are ongoing, but further research into the underlying mechanisms is urgently needed.

The Effects of Heat Stress on the Ovary, Follicles and Oocytes: A Systematic Review.

Climate change is driving significant environmental changes with profound implications for human health, including fertility. Although the detrimental effects of heat on spermatogenesis are well-documented, the impact of elevated temperatures on ovaries and female fertility remains less explored. This systematic review evaluates the effects of elevated temperature exposures (heat stress, HS) on the ovary, follicles, and oocytes across a range of mammalian species. Drawing from both in vivo and in vitro studies, we synthesize findings that show HS can impair ovarian function by disrupting reproductive hormone profiles, reducing ovarian size and weight, altering ovarian histology, and inducing autophagy. At the cellular level, HS leads to increased granulosa cell apoptosis, impaired folliculogenesis, and decreased oocyte quality and developmental competence. However, inconsistencies across studies highlight the influence of experimental variation, including differences in species, timing, intensity, and duration of HS exposure. While many studies report detrimental effects, a few suggest possible adaptive responses under certain conditions. Finally, we review emerging interventions, including antioxidants, hormone supplementation, and bioactive compounds, that aim to counteract HS-related reproductive damage. Despite progress, further research is urgently needed to define conserved molecular pathways, optimize experimental models, and inform clinical strategies to protect fertility and reproductive lifespan in a warming world.

Article	Year
Cumulus expansion is impaired with advanced reproductive age due to loss of matrix integrity and reduced hyaluronan. Aging cell\| PubMed ID: 37850336	2023
The oocyte microenvironment is altered in adolescents compared to oocyte donors. bioRxiv : the preprint server for biology\| PubMed ID: 38617323	2024
Phthalates are detected in the follicular fluid of adolescents and oocyte donors with associated changes in the cumulus cell transcriptome. bioRxiv : the preprint server for biology\| PubMed ID: 38645121	2024
The oocyte microenvironment is altered in adolescents compared to oocyte donors. Human reproduction open\| PubMed ID: 39211054	2024
Phthalates are detected in the follicular fluid of adolescents and oocyte donors with associated changes in the cumulus cell transcriptome. F&S science\| PubMed ID: 39515754	2025
The Effects of Heat Stress on the Ovary, Follicles and Oocytes: A Systematic Review. bioRxiv : the preprint server for biology\| PubMed ID: 39677695	2024
The Effects of Heat Stress on the Ovary, Follicles and Oocytes: A Systematic Review†. Biology of reproduction\| PubMed ID: 40626913	2025

Dilan Gokyer

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