Journal
MOLECULAR HUMAN REPRODUCTION
Volume 19, Issue 8, Pages 519-527Publisher
OXFORD UNIV PRESS
DOI: 10.1093/molehr/gat024
Keywords
AMH; human small antral follicles; granulosa cells; follicular fluid; modelling
Funding
- Danish Cancer Society [DP05112/R2-A41-09-S2]
- The Danish Medical Research Council [271-07-0452, 09-072265]
- UK Medical Research Council [G1100357]
- Novo Nordic Foundation
- Sophus Carl Emil Friis and wife Olga Doris Friis' foundation
- The Lundbeck Foundation
- University Hospital of Copenhagen
- EPSRC [EP/H004092/1] Funding Source: UKRI
- MRC [G1002033, G1002118] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/H004092/1] Funding Source: researchfish
- Medical Research Council [G1100357, G1002118, G1002033] Funding Source: researchfish
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Anti-Mllerian hormone (AMH) is exclusively produced by granulosa cells (GC) of the developing pre-antral and antral follicles, and AMH is increasingly used to assess ovarian function. It is unclear which size follicles make the most AMH (total content) and are the main contributors to circulating AMH concentrations. To determine AMH gene expression in GC (q-RTPCR) and follicular AMH production (Elisa and RIA) in relation to follicular development, 87 follicles (313 mm diameter) including both GC and the corresponding follicular fluid (FF) were collected in connection with fertility preservation of human ovaries. Further, follicle number and diameter, graded in 1 mm increments, were determined by 3D ultrasound in 113 women in their natural menstrual cycle to determine follicle number and diameter in relation to circulating AMH levels. This study demonstrates for the first time a positive association between AMH gene expression in human and both total follicular fluid AMH (P 0.02) and follicular fluid AMH concentration (P 0.01). AMH gene expression and total AMH protein increased until a follicular diameter of 8 mm, after which a sharp decline occurred. In vivo modelling confirmed that 58 mm follicles make the greatest contribution to serum AMH, estimated for the first time in human to be 60 of the circulating concentration. Significant positive associations between gene expression of AMH and FSHR, AR and AMHR2 expression (P 0.00001 for all three) and significant negative association between follicular fluid AMH concentration and CYP19a1 expression were found (P 0.0001). Both AMH gene expression (P 0.02) and follicular fluid concentration of AMH (P 0.00001) correlated negatively with estradiol concentration.
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