Gene Expression Analysis of Human Fetal Ovarian Primordial Follicle Formation

• Published in: The journal of clinical endocrinology and metabolism Vol. 94; no. 4; pp. 1427 - 1435
• Main Authors: Fowler, Paul A., Flannigan, Samantha, Mathers, Anna, Gillanders, Kim, Lea, Richard G., Wood, Maureen J., Maheshwari, Abha, Bhattacharya, Siladitya, Collie-Duguid, Elaina S. R., Baker, Paul J., Monteiro, Ana, O'Shaughnessy, Peter J.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.04.2009
• Subjects: Abortion, Induced; Autoantigens - genetics; Basic Helix-Loop-Helix Transcription Factors - genetics; Biological and medical sciences; Endocrinopathies; Feeding. Feeding behavior; Female; Fetal Development - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression; Humans; Medical sciences; Oocytes - physiology; Ovarian Follicle - physiology; Ovary - physiology; Pregnancy; Pregnancy Trimester, Second; Transcription, Genetic; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Human; Obesity; Nutrition; Nutrition disorder; Metabolic diseases; Gene expression; Pregnancy; Ovary; Female genital system; Fetus; Ovarian follicle; Formation; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2008-2619

Context: Primordial follicle formation dictates the maximal potential female reproductive capacity and establishes the ovarian reserve. Currently, little is known about this process in the human. Objective: The aim of the study was to identify genes associated with the onset of human fetal primordial follicle formation in morphologically normal human fetuses. Design: We conducted an observational study of the female fetal gonad, comparing gene expression before and during primordial follicle formation. Setting: The study was conducted at the Universities of Aberdeen, Glasgow, and Nottingham. Patients/Participants: Ovaries were collected from 51 morphologically normal human female fetuses of women undergoing elective termination of normal second trimester pregnancies. Main Outcome Measures: We performed fetal ovarian transcript expression by Affymetrix array and quantitative RT-PCR and gene product expression and localization by Western blot and immunohistochemistry. Results: Five transcripts were down-regulated and 61 were up-regulated in ovaries from older fetuses (18–20 wk) in which primordial follicle formation had started compared with younger (15–16 wk) fetuses in which no primordial follicles were observed. The altered genes contribute to major functions, including gene expression, tissue morphology, and apoptosis, that are essential for ovarian development. NALP5, the most highly regulated transcript, is an oocyte-specific maternal effect gene that is regulated downstream of FIGLA. Conclusions: NALP5 probably plays a key role in the onset of human primordial follicle formation and thus the establishment of ovarian reserve in women. Transcriptomic analysis of the onset of primordial follicle formation in the human fetal ovary demonstrates up-regulation of 61 genes, including the maternal effect gene NALP5, which may have an important role in this key process.