In-depth analysis of transcriptomes in ovarian cortical follicles from children and adults reveals interfollicular heterogeneity

• Published in: Nature communications 2024-08, Vol.15 (1), p.6989-18, Article 6989
• Main Authors: Rooda, Ilmatar, Hassan, Jasmin, Hao, Jie, Wagner, Magdalena, Moussaud-Lamodière, Elisabeth, Jääger, Kersti, Otala, Marjut, Knuus, Katri, Lindskog, Cecilia, Papaikonomou, Kiriaki, Gidlöf, Sebastian, Langenskiöld, Cecilia, Vogt, Hartmut, Frisk, Per, Malmros, Johan, Tuuri, Timo, Salumets, Andres, Jahnukainen, Kirsi, Velthut-Meikas, Agne, Damdimopoulou, Pauliina
• Format: Article
• Language: English
• Subjects: 13/51; 38/1; 38/32; 38/39; 49/91; 631/1647/2017; 631/337/2019; 631/443/494; 692/308/3187; 692/698/1460/1527/1710; Adolescent; Adult; Adults; Child; Child, Preschool; Children; Chronology; Cryopreservation; Cyclophosphamide; Extracellular matrix; Female; Fertility; Fertility Preservation - methods; Follicles; Gametocytes; Gene Expression Profiling; Heterogeneity; Humanities and Social Sciences; Humans; Medical treatment; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; multidisciplinary; Oocytes - metabolism; Ovarian Follicle - metabolism; Ovaries; Science; Science (multidisciplinary); Signal Transduction; Theca; Transcription activation; Transcriptome; Transcriptomes
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-51185-0

The ovarian cortical reserve of follicles is vital for fertility. Some medical treatments are toxic to follicles, leading to premature ovarian insufficiency. Ovarian tissue cryopreservation is an established method to preserve fertility in adults and even applied in prepuberty despite unproven efficacy. Here, we analyze transcriptomes of 120 cortical follicles from children and adults for detailed comparison. We discover heterogeneity with two main types of follicles in both age groups: one with expected oocyte-granulosa profiles and another with predicted role in signaling. Transcriptional changes during growth to the secondary stage are similar overall in children and adults, but variations related to extracellular matrix, theca cells, and miRNA profiles are found. Notably, cyclophosphamide dose correlates with interferon signaling in child follicles. Additionally, morphology alone is insufficient for follicle categorization suggesting a need for additional markers. Marker genes for early follicle activation are determined. These findings will help refine follicular classification and fertility preservation techniques across critical ages. The ovarian cortical reserve of follicles is vital for fertility. Here, Rooda et al. find two distinct follicle types in the human ovarian reserve, as well as key differences between child and adult follicles, calling for more precise follicle analysis in fertility preservation and continued research on their roles in fertility.