Anti-Müllerian hormone (AMH), also known as Müllerian duct inhibitor, is a member of the transforming gonadotropic superfamily. Both gonadal cells secrete AMH, but the amount of the secretory phase varies. In males, it is secreted by the immature supporting cells of the testis and has the effect of degenerating the male embryonic Müllerian duct; in females, it is mainly secreted by the granulosa cells of the antral follicles and the small sinus follicles, and is closely related to ovarian function and regulates follicular growth and development.
Physiological effects of anti-mullerian hormone (AMH).
1. Inhibition of mullerian duct development
In humans, sexual differentiation generally begins at 7w of gestation, and AM has an effect on the embryonic Mullerian ducts of both sexes: in males, when androgens stimulate the development of Mullerian ducts, AMH stimulates fibroblasts to proliferate, prompting Mullerian ducts to degenerate, while Mullerian ducts differentiate into epididymal ducts, vas deferens, seminal vesicles, and ejaculatory ducts. In women, due to the lack of androgen and AMH, the ducts degenerate into the uterus, fallopian tubes and upper vagina.
2.Regulate the development of gonads and germ cells
AMH inhibits the development of gonads in both sexes: AMH mainly degenerates Mullerian ducts in male sexual differentiation and reduces steroid hormone enzymes by blocking the differentiation of Leydig cells in testes, which affects the development and function of testes; after birth, it also plays a role in gonadal development, regulation of germ cells and induction of testicular descent. AMH also has a regulatory role in early sperm formation and maturation.
In females, AMH is secreted by ovarian granulosa cells in the postnatal growth follicles. It inhibits luteinizing hormone receptor and luteinizing hormone biosynthesis on ovarian granulosa cells, regulates oogenesis and cell meiosis, inhibits granulosa cell proliferation and follicle maturation, and plays an important role in the selection of mature follicles. In human ovarian tissue studies, AMH expression was absent in the basal follicles, weakly expressed in the granulosa cells of 74% of the primary follicles, strongly expressed in the secondary follicles, antral follicles and 4 mm small sinus follicles, and gradually disappeared in the larger sinus follicles (4-8 mm), almost absent in follicles >8 mm, and absent in atretic follicles.
The AMH in human small sinus follicles (3-8 mm) is 3 times higher than that in preovulatory follicles. The ovaries have high aromatase activity, which converts testosterone to androgens, while AMH inhibits the synthesis of P450 aromatase in granulosa cells, thus hindering the conversion of androgens to estrogens, and reduces the number of LH receptors, inhibiting the production of progesterone.
3. Other effects of AMH
AMH has the function of inhibiting the growth and differentiation of certain tumor cells, as well as inhibiting the accumulation of substances on the surface of the lung and inhibiting fetal lung maturation.
Applications of AMH in assisted reproductive technology
1. AMH and ovarian reserve function
Ovarian reserve refers to the ability of follicles in the ovarian cortex to grow, develop, and form fertilizable oocytes, as evidenced by the number of follicles present in the ovary and the quality of the eggs within them. During in vitro fertilization-embryo transfer, assessing ovarian reserve function and predicting ovarian responsiveness to ovulation-promoting drugs is a crucial prerequisite and one of the current challenges in reproductive medicine.
The quantity and quality of follicles developed by exogenous gonadotropin stimulation varies among patients, and ovarian responsiveness is mainly determined by the quantity and quality of oocytes, i.e. ovarian reserve function.
AMH is an active factor secreted by ovarian granulosa cells, and is expressed in follicles recruited from the basal follicular pool until they are selected to become the dominant follicle, and is weakly expressed in granulosa cells of primary follicles, highly expressed in granulosa cells of antral follicles and small sinus follicles, and not expressed in basal follicles atretic follicles and follicular membrane cells.
In women with normal ovulation, serum AMH levels change earlier on day 3 of menstruation with increasing age than other known hormonal markers, such as inhibin B and FSH, suggesting that serum AMH levels better reflect the number of ovarian sinus follicles and provide a more accurate diagnosis of ovarian reserve function in women with normal menstruation but reduced fertility.
2. Assisted reproduction outcome prediction
With the continuous development of assisted reproductive technology, IVF-ET has become an important tool in the treatment of infertility. Successful IVF-ET clinical pregnancy is the result of the combination of high-quality embryos, normal endometrial tolerance and good endocrine levels. In recent years, AMH has received considerable attention in the field of female reproduction. The relationship between AMH and IVF treatment outcome has its own specificity, and studies have found that basal serum AMH levels are the only predictor of IVF pregnancy.
3. AMH and male reproduction
Spermatogenesis is a highly ordered process of cell development and differentiation, and spermatogenesis is a hormone-dependent process. Hormones mainly regulate spermatogenesis through the hypothalamic-pituitary-gonadal axis, i.e. gonadotropin-releasing hormone (GnRH) secreted by the hypothalamus, follicle-stimulating hormone (FSH), luteinizing hormone (LH) secreted by the pituitary gland, and testosterone (T) secreted by the testicular interstitial cells are the regulatory hormones of spermatogenesis. However, FSH and T do not act directly on spermatogenic cells, but bind to the corresponding receptors on testicular supporting cells to produce effectors that nourish spermatogenic cells and regulate the spermatogenic process through paracrine action.
The presence of AMH in seminal plasma is due to the existence of blood-testis barrier in testicular tissues, which makes it difficult for large molecules of AMH to escape into the blood circulation, and therefore the level of seminal plasma AMH is much higher than the serum level.