Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection

Abstract

Anti-Müllerian 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-RT-PCR) and follicular AMH production (Elisa and RIA) in relation to follicular development, 87 follicles (3-13 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 5-8 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.

A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure

“…Similar patterns occur in non-human primates (Modi et al 2006), mice (Gruijters et al 2003), rats (Ueno et al 1989, Hirobe et al 1994, Baarends et al 1995, Siberian hamsters (Shahed & Young 2013), cows (Monniaux et al 2012), goats (Monniaux et al 2012, Rocha et al 2016, sheep (Bezard et al 1987) and brushtail possums (Juengel et al 2002). AMH expression declines as follicles progress through the large antral stage of folliculogenesis, with little AMH being produced in preovulatory follicles (Ueno et al 1989, Weenen et al 2004, Jeppesen et al 2013. However, AMH expression remains elevated in the cumulus granulosa cells of large follicles until immediately prior to ovulation (Ueno et al 1989, Hirobe et al 1994, Monniaux et al 2012, Merhi et al 2013.…”

Hormon anty-müllerowski i zespół policystycznych jajników

“…A positive relationship between AMH and AFC has been demonstrated in a large number of studies, which indirectly reflects ovarian reserve. Variability in the number of antral follicles may result in AMH level differences [18][19][20][21]. Recent studies indicate that AMH concentration may vary according to the ethnicity, with lower serum AMH level in African-American and Hispanic women in comparison to Caucasian women [22,23].…”

Effect of growth hormone receptor gene disruption and PMA treatment on the expression of genes involved in primordial follicle activation in mice ovaries

“…AMH is exclusively produced by developing preantral and small antral follicles (Jeppesen et al 2013), and it is used to estimate the size of the ovarian reserve (Visser et al 2006). GDF9 and BMP15 are also produced exclusively by growing oocytes in the mouse ovary (McGrath et al 1995;Dube et al 1998) and are involved in follicle maturation and oocyte quality (Dong et al 1996;Yan et al 2001).…”