Ovarian follicular development

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Anti mullerian hormone (AMH) is a glycoprotein which is produced by the granulosa cells of ovarian follicles in adult women belongs to the superfamily of growth and differentiation factors called transforming growth factor- beta (Durlinger et al.1999 and Fleming et al.2006). AMH plays a vital role in ovarian follicular development at two different but critical points. AMH acts as an inhibitor of primordial follicle recruitment and also decreases the effect of follicle stimulating hormone (FSH) on follicle growth (Durlinger et al.2002b and Durlinger et al. 2001).

AMH inhibition of primordial follicle recruitment

The role which is played by AMH in the ovary was obtained by carrying out studies on mice. Primordial follicles in mice form straight after birth. Within the pool of the primordial follicles all the ovarian follicles required during reproductive life. Primordial follicles begin to grow as they come into existence in the ovary, however not all follicles grow at the same speed; some may not grow and remain at rest for months in mice and years in humans. Factors regulating primordial follicle growth are still unknown.

Durlinger et al. 2002b carried out tests on ovaries taken from 2 day old mice to know what effect AMH has on primordial follicles. 2 day old mice ovaries were good choice for study as they contained high number of primordial follicles and no growing follicles. After 2 to 4 days of culture it was noticed that ovaries with AMH had fewer follicles compared to ovaries without AMH. These findings indicate that AMH does inhibit primordial follicle recruitment. When primordial follicle growth occurs along with AMH, alpha inhibin protein is also released by the granulosa cells of primordial follicles which have grown. The inhibitory effect of AMH on primordial recruitment is further showcased by decreasing levels of the alpha inhibin protein released (Durlinger et al. 2002b).

To understand the role of AMH in the ovary, the total follicle population was calculated in three different mice. The three mice used were AMH null mice, mice which are heterozygous for AMH null mutation and wild type mice. The mice which were used were at different stages of life25 days, 4 months and 13 months. Higher numbers of preantral and small antral follicles were found in the ovaries of 25 days and 4 months old AMH null female mice compared to wild type females. AMH null females' mice aged 4 and 13 months had the fewer number of primordial follicles. Also no primordial follicles found AMH null females aged 13 month, they also had small number preantral and antral follicles. The findings of heterozygous were in between null and wild type mice. Comparing the serum inhibin levels of 4 month old AMH null mice and wild type mice, it was found that 4 month old AMH null mice had the higher levels. On the other hand the lower serum inhibin levels were found in AMH null mice females. From this study it was concluded that AMH plays a major role in primordial recruitment as more primordial follicles are recruited in AMH null mice than in wild type mice (Durlinger et al.1999).

AMH decreases effect of FSH

Studies has shown that AMH as well as playing a role in primordial follicle recruitment, it also plays a major part in decreasing the effect of FSH on the growing follicles. In the same study as the AMH null mice females and wild type it was seen that 4 month old ovaries which had AMH absence had more follicles growing than the wild type with AMH. These results show that AMH does inhibit follicle growth induced by FSH showing that the effect of FSH is decreased.

A different study showed contrasting results to the AMH null mice females. This study showed that AMH acts as a FSH induced follicle growth stimulator. Although both studies used preantral follicles the contrasting results could be due to the difference in the species used and whether serum was present in the culture or not (Durlinger et al.1999 and Mcgee et al.2001).

A different study was carried out to see what effect AMH has on the response of follicle growth to FSH. It was found that females without AMH had more follicles which started to grow than females with AMH. These results indicate that the response of follicle growth to FSH is weakened when AMH is present. During this study it was also observed that the recruitment of primordial follicles further decrease in mice with AMH deficeincy when FSH is also absent. From this study it was concluded that AMH decrease the effect of FSH on follicle growth as the follicles are less reponsive to FSH and AMH is a regulating factor in early follicle growth. The action of AMH as regulating factor of early follicle growth is further shown in the study to determine the follicle population of 4 month old FSH beta deficient mice and wild type mice. This study showed that FSH has no effect on how many preantral small antral follicles and primordail follicles there are. In this same study it was seen that female mice without both FSH beta and AMH deficieny, the phenotype of ovary due to AMH deficieny was more noticleable. This shows that AMH may be stronger regulator of foolice growth than FSH (Durlinger et al. 2001).

References

  • Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT,Grootegoed JA & Themmen AP (1999) Control of primordial follicle recruitment by anti-Mullerian hormone in the mouse ovary. Endocrinology 140 5789-5796
  • Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham HA, Nachtigal MW, Uilenbroek JT, Grootegoed JA & Themmen AP (2002b) Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology 143 1076-1084
  • Durlinger AL, Gruijters MJ, Kramer P et al. (2001) Anti-Müllerian hormone attenuates the effects of FSH on follicle development in the mouse ovary Endocrinology 142 4891-4899
  • McGee EA, Smith R, Spears N, Nachtigal MW, Ingraham H and Hsueh AJ (2001) Müllerian inhibitory substance induces growth of rat preantral ovarian follicles Biology of Reproduction 64 293-298

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