Synthesis and functions

AMH is a dimeric glycoprotein of 144 kDa, composed of two subunits of 72 kDa, belonging to the superfamily of the transforming growth factor-β (TGF-β) (Bedenk et al., Reference Bedenk, Vrtačnik-Bokal and Virant-Klun2019). Bone morphogenetic protein 15 (BMP15) is also part of this family, involved in folliculogenesis; the growth and differentiation 9 factor (GDF9) affects the growth and differentiation of oocytes and interferon-T (IFN-T), with various physiological functions in the mammalian uterus (D’Occhio et al., Reference D’Occhio, Campanile and Baruselli2020). AMH is derived from a precursor that exhibits slight variations between species, from 553 amino acids in rats to 575 amino acids in bovines. The latter being similar to the precursor of equines with 573 amino acids (Josso et al., Reference Josso1993). The AMH precursor starts with a signal sequence of 16–17 amino acids, followed by a prosequence of 7–8 amino acids, which are cleaved from the precursor before secretion (Claes and Ball, Reference Claes and Ball2016). In the cytoplasm, the inactive precursor undergoes an obligatory cleavage (Arouche et al., Reference Arouche2015) and an N-terminal fragment of 110 kDa (pro region) and another C-terminal of 25 kDa (mature or native region) are generated (Capecce et al., Reference Capecce2016). These fragments are linked in a non-covalent complex by two disulphide bonds (Arouche et al., Reference Arouche2015).

The AMH was discovered in 1947 by Alfred Jost (Bedenk et al., Reference Bedenk, Vrtačnik-Bokal and Virant-Klun2019), and since then it has been known to play a vital role in the sexual development of the foetus. AMH expression is strong in foetal testes but absent in ovaries (Scarlet et al., Reference Scarlet2021). It is secreted by the testicular Sertoli cells, producing the degeneration of the Müllerian ducts in male embryological development (Capecce et al., Reference Capecce2016; Josso et al., Reference Josso2006). In women, AMH is not expressed during the time of sexual differentiation, ensuring the normal development of the female genital tract (Almeida et al., Reference Almeida2011; Hirobe et al., Reference Hirobe1992; Taketo et al., Reference Taketo1993). In the last 15 years, the relevance and importance of this hormone as an ovarian function marker has been increasing (Capecce et al., Reference Capecce2016). AMH is produced in female mammals by the granulosa cells. So that, the primary follicle is the first type of follicle expressing this hormone, and as the number of granulosa layers increases, the expression of AMH does so (Claes and Ball, Reference Claes and Ball2016). It has been shown that AMH intervenes in the inhibition of the primordial follicle growth, preventing premature depletion of the ovarian follicle reserve (Mossa et al., Reference Mossa2017), and that it triggers a decrease in the responsiveness to follicle-stimulating hormone (FSH) in the antral and preantral follicles, modulating follicular development (Dewailly et al., Reference Dewailly2014; Mossa et al., Reference Mossa2017). Consequently, AMH determines which follicles are selected for further growth and which become atretic (Nawaz et al., Reference Nawaz2018). In the absence of AMH, follicles are recruited at a faster rate, which results in a depletion of primordial follicles at a younger age (Mossa et al., Reference Mossa2017). Another of its functions is the decrease in aromatase activity, which reduces oestradiol production (Dewailly et al., Reference Dewailly2014; Łebkowska et al., Reference Łebkowska2024), and stimulation of testosterone production by theca cells (Capecce et al., Reference Capecce2016).

Expression of AMH in female mammals

AMH expression in granulosa cells is timely and especially dynamic during follicular development, being inversely related to aromatase expression and oestradiol production (Ireland et al., Reference Ireland2009; Monniaux et al., Reference Monniaux2013; Ribeiro et al., Reference Ribeiro2014). AMH production starts immediately at the time follicles are initially recruited, reaching its highest level in primordial follicles. Subsequently, it decreases at the same time as the FSH-dependent follicle progresses towards the preovulatory stage (Mossa et al., Reference Mossa2017). AMH is not produced by atretic follicles, so that it is a reflection of the amount of antral follicles that are healthy and growing (Daly et al., Reference Daly2020). Different research groups have evaluated the concentration of circulating AMH in the mammalian species analysed in this review. In Table 1, we can see the results that they have obtained in their studies.

Table 1. Studies that have analysed the concentration of AMH (Mean ± SD) in women, mare, and cow (dairy and beef cows)

Despite the fact that all studies used ELISA as the analysis method, these results are not comparable. In each study, a different number of samples were collected and the age of the populations used is different.

As can be seen in Table 1, not only the species causes AMH concentrations to differ but also the breed and age produce variations in this hormone.

With respect to dairy cows, it has been confirmed that these present a lower AMH concentration than beef cows (Mossa et al., Reference Mossa2017). Also, there is a great phenotypic variation in the circulating AMH concentrations, depending on the breed. Jersey cows have the highest concentration, followed by crossbreds and lastly, Holstein cows (Gobikrushanth et al., Reference Gobikrushanth2019) (Table 2).

Table 2. AMH concentration in different breeds of dairy cows, obtained in the study carried out by Gobikrushanth et al. (Reference Gobikrushanth2019)

Serum AMH concentration from 2,628 dairy cows was analysed using bovine AMH ELISA (Gobikrushanth et al., Reference Gobikrushanth2019).

Although in general, the AMH concentration has been found to remain stable and repeatable over many oestrous cycles (Mossa et al., Reference Mossa2017), it has been observed that its concentration is inversely related to age.

In women, serum AMH levels increase until the third decade of life and slowly decrease with age (Gouvea et al., Reference Gouvea, Cota, Souza and Lima2022). Liebenthron et al. (Reference Liebenthron2019), obtained the maximum AMH concentration, of 5.71 ± 6.78 ng/ml in girls between 6 and 10 years of age. This concentration was reduced when the woman’s age was between 41 and 45, obtaining a mean of 1.2 ± 0.85 ng/ml (Liebenthron et al., Reference Liebenthron2019). Similar results are obtained by Ji et al. (Reference Ji2022) in their study, seeing that the concentration of AMH decreased with increasing age, especially after 40 years (Ji et al., Reference Ji2022). AMH was also shown to be the most promising predictive marker for detection of ovarian aging and the time of the menopause (Racoubian et al., Reference Racoubian2020), being used as a support criterion for the classification in the stages of reproductive aging (Gouvea et al., Reference Gouvea, Cota, Souza and Lima2022). Likewise, there are authors who affirm that the concentration of AMH potentially predicts the age of menopause (Broer et al., Reference Broer2011; Eskew et al., Reference Eskew2022). Although, regarding the latter, the usefulness of AMH as a predictive marker does not offer definitive conclusions (Yoon et al., Reference Yoon2020).

The same thing happens in cattle, both in dairy and beef cows. During the first months of life, the AMH concentration is at maximum levels, decreasing at 5 months and remaining stable at 8–9 months, around the time of the first ovulation (Mossa et al., Reference Mossa2017). In the study by Lainé et al. (Reference Lainé2019), it was observed that in the ovaries of 3-month-old calves, the population of follicles of 3–5 mm contained high AMH concentrations. In addition, their number was closely related to the plasma concentration of this hormone (Lainé et al., Reference Lainé2019).

In mares, serum AMH concentrations also correlate with age (Nolan et al., Reference Nolan2018). As in the rest of the species mentioned, the lowest AMH concentrations are obtained in older ones (19–27 years). But in this species, the highest AMH concentration is found in middle-aged mares (9–18 years) instead of in young ones (3–8 years) (Claes et al., Reference Claes2015). Similar results are reported in the study carried out by Uliani et al. (Reference Uliani2019), in which they collected data on AMH concentrations throughout the life of 1,101 mares, sampled from birth to an age greater than 33 years. They obtained that the concentrations of AMH were higher in mares of 5–10 years and 10–15 years than in mares of 0–5 years and the lowest in mares of 20 years or more (Uliani et al., Reference Uliani2019).

Despite the fact that in all the aforementioned studies, there is a decrease in AMH with increasing age, these results are not comparable since the same analysis protocol has not been followed.

On the other hand, although it is not the subject of this review, it is also necessary to consider, that there are external factors that can affect both the circulating concentrations of AMH and those of its main receptor, anti-Mullerian hormone receptor 2 (AMHR2). In this sense, the study carried out by Saleh et al. (Reference Saleh2021) shows that exposure to chemicals such as bisphenol A leads to an alteration in the expression of both AMH and its receptor, at the mRNA and protein level in both oocytes and blastocysts (Saleh et al., Reference Saleh2021). This highlights the adverse effects that contact with chemicals, as well as pollution, can have on female reproductive health (Han et al., Reference Han2024).

AMH receptor type 2

Signalling within the TGF-β family is limited to specific combinations of the seven type I receptors, activin-like kinases 1–7 (ALK1–7), and five type II receptors, ActRIIA, ActRIIB, BMPR2, TβR2, and AMHR2 (Hinck et al., Reference Hinck, Mueller and Springer2016; Howard et al., Reference Howard, Hart and Thompson2022). AMH uses type I receptors, specifically ALK2 and ALK3, to send signals. However, the main AMH receptor is AMHR2, which is specific to this hormone (Howard et al., Reference Howard, Hart and Thompson2022). Given the growing interest in AMH, the role of its specific receptor, AMHR2, has begun to be studied (Figure 1).

Figure 1. Human chromosome in which the gene of AMHR2 is found. An image obtained from the NCB1 database (https://www.ncbi.nlm.nih.gov/gene?db=gene&cmd=detailssearch&term=269).

Most of the studies carried out to date have focused on the place in which it is expressed and its relationship with reproduction.

In the adult human brain, it has been shown that, in mature neurons, AMH receptors are expressed both in men and women. AMHR2 is the most expressed receptor in different brain areas and cell types involved in the central control of reproduction, among which the vascular organ of the lamina terminalis is included (Barbotin et al., Reference Barbotin2019).

A previous study by Kereilwe et al. (Reference Kereilwe2018) investigated in postpuberal heifers whether their AMHR2 was expressed in the gonadotrophs to control the secretion of gonadotropins. By carrying out the polymerase chain reaction, they confirmed that the mRNA of this receptor was expressed in the anterior pituitary gland. In this place the gonadotrophs are found. In addition, by immunofluorescence microscopy, they verified that there was a co-localization of the AMHR2 and of the gonadotropin-releasing hormone (GnRH) receptor in the plasmatic membrane of the gonadotrophs (Kereilwe et al., Reference Kereilwe2018). Based on these results, it can be said that AMHR2 controls together with GnRH, gonadotroph secretion and that AMHR2 is also expressed in extragonadal areas. Therefore, Ferdousy et al. (Reference Ferdousy, Kereilwe and Kadokawa2020) conducted a study to find out whether there was any expression of mRNA in oviductal and endometrial samples in Holstein and Wagyu cows. By immunohistochemical, a large expression of AMH and AMHR2 in the ampulla and isthmus mucosa, and in the glandular and luminal epithelium of the endometrium, were revealed (Ferdousy et al., Reference Ferdousy, Kereilwe and Kadokawa2020).

Very recent studies, that continue these investigation lines, have confirmed the action mechanisms of AMH and AMHR2 in extragonadal areas. The gonadotrophs express AMH to exert paracrine and autocrine functions (Kereilwe and Kadokawa, Reference Kereilwe and Kadokawa2020a). AMH stimulates the GnRH neurons through its receptor. Most of the GnRH neurons in the preoptic area, arched nucleus and median eminence present AMH and AMHR2 expressions (Kereilwe and Kadokawa, Reference Kereilwe and Kadokawa2020b). These areas in the brain are relevant for the neuroendocrine control of reproduction (Kereilwe and Kadokawa, Reference Kereilwe and Kadokawa2020a). Ferdousy et al. (Reference Ferdousy, Kereilwe and Kadokawa2020) also found that there is a lower expression of AMH and AMHR2 in the posterior hypothalamus of old cows compared to young cows, finding a correlation between aging and both proteins (Kereilwe and Kadokawa, Reference Kereilwe and Kadokawa2020b). However, despite the information reported, in general, more studies are needed to analyse the action mechanisms of AMH and AMHR2 in the hypothalamus and their influence on the secretion of GnRH and gonadotropins (Kereilwe and Kadokawa, Reference Kereilwe and Kadokawa2020a).

Gonadotropins

The FSH and the luteinizing hormone (LH) are two gonadotropins secreted by the pituitary gland that control the function of the gonads, both the male and female ones. In women, the granulosa cells of all the growing follicles present receptors for FSH, and theca cells have receptors for LH (Lainé et al., Reference Lainé2019).

Khodavirdilou et al. (Reference Khodavirdilou2022) show that AMH levels differ between follicular and luteal phase, which could be due to ovarian response to gonadotropins (Khodavirdilou et al., Reference Khodavirdilou2022). Based on studies performed up to date, it appears that the expression of the AMH is reduced in the FSH-dependent stages of follicle development (Ball et al., Reference Ball2008). A high FSH concentration suppresses the expression of AMH directly or indirectly through oocyte-specific growth factors, triggering a marked decrease in AMH levels (Robertson et al., Reference Robertson, Lee and Baerwald2020).

In women, there is an inverse correlation between FSH and AMH, but the interaction between FSH, AMH, AFC, and the follicle growth dynamics has not been completely understood (Robertson et al., Reference Robertson, Lee and Baerwald2020). In the absence of AMH, the FSH-dependent phases’ folliculogenesis become more sensitive to FSH, and more follicles grow to be dominant ones. So that, it could be said that AMH exerts a paracrine role in the regulation of the sensitivity to FSH and the recruitment of follicles (Robertson et al., Reference Robertson, Lee and Baerwald2020). In this sense, AMH would act by repressing the recruitment, selection, and maturation of follicles, by inhibiting the action of FSH (Baarends et al., Reference Baarends1995; Durlinger et al., Reference Durlinger2002; Gouvea et al., Reference Gouvea, Cota, Souza and Lima2022; Gruijters et al., Reference Gruijters2003).

In ruminants, preantral and antral follicles can secrete AMH to control gonadotropins secretion in the gonadotrophs (Kereilwe et al., Reference Kereilwe2018). In the study carried out by Lainé et al. (Reference Lainé2019), they determined that, before 3 months of age, two out of every six calves showed a clear peak of postnatal FSH in plasma. However, they did not find any relationship between the FSH concentration and AMH (Lainé et al., Reference Lainé2019). Similarly, Krause et al. (Reference Krause2022) did not find a correlation between plasma FSH concentrations and AMH in prepubertal calves (Krause et al., Reference Krause2022). The relationship of the FSH concentration to ovarian follicle dynamics is not yet understood in young calves. This is because they experience different patterns of FSH secretion, and the postnatal activation of the follicle growth up to the antral phase seems to be independent of the FSH levels (Lainé et al., Reference Lainé2019).

In mares, no relationship has been established between the AMH and the FSH concentrations (Ball et al., Reference Ball2019).

With regard to LH, there are not many studies that relate its concentration to that of AMH. Kereilwe et al. (Reference Kereilwe2018) were able to confirm that AMH stimulated, though weakly, basal LH secretion in heifers (Kereilwe et al., Reference Kereilwe2018). A recent study made by that same author on Japanese black cows found that AMH stimulates LH secretion in bovine gonadotrophs (Kereilwe and Kadokawa, Reference Kereilwe and Kadokawa2020b).

Steroid hormones

Within the steroid hormone group, oestradiol (E2) is one of those most studied in relation to AMH because it is the hormone responsible for the growth and development of reproduction organs, as well as of the ovarian follicles (Steel et al., Reference Steel, Athorn and Grupen2018). This hormone is associated with the reproductive qualities in cows and humans. It marks the antral follicle populations in the animals and the pregnancy results in women after gonadotropin treatment (Steel et al., Reference Steel, Athorn and Grupen2018).

In women, low AMH levels have been associated with the increase in E2 concentrations (Ishii et al., Reference Ishii2019). However, in cows, the production of E2 and AMH was positively related, since the cow granulosa cells with a high AFC produce larger amounts of both hormones (Sakaguchi et al., Reference Sakaguchi2019).

With respect to progesterone (P4), it is known that its levels have an influence on fertilization rates and on the embryo parameter quality. Also, some studies report that intrafollicular P4 and AMH affect women’s fertility (Daly et al., Reference Daly2020). A recent study performed on humans demonstrated that AMH inhibits the P4 synthesis (Robertson et al., Reference Robertson, Lee and Baerwald2020). However, Ball et al. (Reference Ball2019) report that, in cows, a decrease in AFC related to low levels of AMH causes perturbations in the follicular and also in the luteal functions which gives rise to a decline in P4 concentration (Ball et al., Reference Ball2019).

There is not much bibliography relating AMH and P4, so that it is difficult to arrive at any conclusion on the influence one might have on the other. More studies are needed that supply more information on this subject.

Relationship of AMH with the ovarian reserve

Effect of age on ovarian reserve

The development of the ovaries and the follicles occurs during the foetal period (Akbarinejad et al., Reference Akbarinejad2018). So that, at birth, mammals present a limited number of ovary germinal cells that drastically decrease with age and are also highly variable between individuals (Lahoz et al., Reference Lahoz2012) (Table 3). In the first days of life, oocytes are housed in the primordial follicles at rest and at an early growth which constitutes the so-called ovarian follicular reserve (Lahoz et al., Reference Lahoz2012; McNatty et al., Reference McNatty1995) AMH is a significant determinant of reproductive aging, which is the age-related depletion of the ovarian follicular reserve (Ramesha et al., Reference Ramesha2022).

Table 3. Variation in the ovarian reserve. Differences in the woman’s, cow’s, and mare’s ovarian reserve at birth and as from 1 year

As can be observed in Table 3, in all the species a diminution is produced of the ovarian follicular reserve with the increase in age. In cows, for example, it has been reported that at 1 year they lose 80% of their original ‘stock’ of oocytes (Ireland et al., Reference Ireland2011). In women, age is considered to be the main factor related to oocyte quality (Massarotti et al., Reference Massarotti2020). It has also been seen that as they get older, the levels of AMH decline. This process is related to the decrease of the ovarian reserve, represented by the quality of the oocytes and the amount of follicles, which results in a decline in the reproductive function of women (Lahoz et al., Reference Lahoz2012; Te Velde and Pearson, Reference Te Velde and Pearson2002). Women have a larger ovarian reserve in comparison with other species (Steel et al., Reference Steel, Athorn and Grupen2018).

With reference to mares, despite their having a longer reproductive life than other species, they have a smaller and more variable ovarian reserve. This might become a clinical problem since a depletion of the ovarian reserve might be produced before the end of their reproductive life (Ball et al., Reference Ball2019). AMH can reflect ovarian senescence in mares after 20 years of age, but is too variable to do so in the first two decades of life (Uliani et al., Reference Uliani2019).

Relationship between AMH and AFC

The ovarian follicular reserve has a direct impact on the ovarian function and on fertility (Lahoz et al., Reference Lahoz2012). In humans, precise information on the ovarian reserve since childhood up to the end of the reproductive stage is of great clinical importance as it may turn out to be useful in cases of IVF (Liebenthron et al., Reference Liebenthron2019). Since AMH was perceived to be involved in the regulation of follicle growth, it has begun to be used for the study of the ovarian reserve and ovarian response. It was discovered that there is a relationship between the concentration of circulating AMH, AFC and the number of primary follicles in women (Capecce et al., Reference Capecce2016; Claes and Ball, Reference Claes and Ball2016). Regarding bovines, this can be phenotyped in terms of the number of antral follicles that grow during the follicular waves. During the latter, AFC is highly variable between individuals but very repeatable in each one (Mossa and Ireland, Reference Mossa and Ireland2019). Heifers with a low AFC show less than 15 follicles of over 3 mm and those with a high AFC have over 25 follicles of over 3 mm (Mossa and Ireland, Reference Mossa and Ireland2019). Furthermore, it has been possible to verify that the young-adult bovines with a low AFC have smaller gonads (Ireland et al., Reference Ireland2011), a thinner endometrium, a decrease in granulosa, thecal, and luteal cell response to FSH and LH, a poor response to superovulation (Mossa and Ireland, Reference Mossa and Ireland2019) and a markedly diminished ovarian reserve. These phenotypic characteristics normally correlate with aging or ovarian infertility (Ireland et al., Reference Ireland2011). Related to the above, Widodo et al. (Reference Widodo2022) hypothesized that ovarian size increased concomitantly with increased AFC in cattle, resulting in an association between ovarian size and blood AMH levels (Widodo et al., Reference Widodo2022). It should be noted that those animals that have a high AFC show a higher reproductive performance (Sakaguchi et al., Reference Sakaguchi2019). In cows, the AMH concentration in serum seems to reflect the follicle population and is also correlated with AFC (Ball et al., Reference Ball2019) detectable by vaginal ultrasound (Arouche et al., Reference Arouche2015). In the study made by Sakaguchi et al. (Reference Sakaguchi2019), it was confirmed that the granulosa cells in cows with a high AFC were capable of producing large amounts of AMH (Sakaguchi et al., Reference Sakaguchi2019). Likewise, Krause et al. (Reference Krause2022) obtained a positive correlation between AFC and plasma concentrations of AMH at the moment of the appearance of the follicular wave, in heifers (Krause et al., Reference Krause2022). Similarly, various studies have reported the existence of a positive and significant correlation between AMH and AFC in Holstein dairy heifers and in Zebu beef cattle (Baldrighi et al., Reference Baldrighi2014; Carter et al., Reference Carter2016; Torres-Simental et al., Reference Torres-Simental2021).

In mares, the circulating concentration of AMH is positively correlated with the number of small growing follicles (Joonè et al., Reference Joonè2018, Reference Joonè2019). Likewise, the determination of the concentration of AMH at a prepubertal age allows to predict the levels of AMH and AFC that will be after puberty (Scarlet et al., Reference Scarlet2018). AMH and AFC concentrations show a high repeatability in different oestral cycles. According to the work done by Ball et al. (Reference Ball2019), there is a strong relationship between both parameters in old mares, a moderate one in middle-aged ones and a non-significant one in young mares. In this sense, Traversari et al. (Reference Traversari2019) show a high interindividual variability in the concentration of AFC and AMH and a positive correlation between both parameters, this correlation being stronger in mares older than 18 years (Traversari et al., Reference Traversari2019). These results are opposite to those reported by Scarlet et al. (Reference Scarlet2018) that show a highly positive correlation between AMH and AFC in young mares (Scarlet et al., Reference Scarlet2018). These contradictory results could be due to the fact that the evaluation of follicle populations together with AMH concentrations is a complex process in mares, given their size, shape and organization of the ovary (Uliani et al., Reference Uliani2019).

Polycystic ovary syndrome

The PCOS is the most common endocrine disorder in women of a reproductive age, with a prevalence of 10–15% worldwide (Moolhuijsen and Visser, Reference Moolhuijsen and Visser2020) and with a highly hereditary component (Barbotin et al., Reference Barbotin2019). Furthermore, it is a very heterogeneous disease, whose exact physiopathological mechanisms are unknown (Moolhuijsen and Visser, Reference Moolhuijsen and Visser2020).

PCOS is associated with high AMH levels since the women who suffer from it present a follicle density that is six times greater than normal ovaries. Women with PCOS have a mean concentration of AMH of between 3.14 and 4.45 ng/ml, although on some occasions it can be higher (Bedenk et al., Reference Bedenk, Vrtačnik-Bokal and Virant-Klun2019). This is proven in various studies such as the one carried out by Butt et al. (Reference Butt2022), in which they obtained a mean serum AMH level of 7.23 ± 4.67 ng/ml in women with PCOS and normal sex hormone levels. In this study, a significant difference in ovarian morphology was also observed between women with PCOS and women without PCOS (Butt et al., Reference Butt2022). Similarly, Muharam et al. (Reference Muharam2022) found that the median AMH level was significantly higher in the PCOS group (7.59 ± 4.61 ng/ml) (Muharam et al., Reference Muharam2022). Likewise, Liu et al. (Reference Liu2022) show that AMH levels were related to the severity of PCOS and the status of the menstrual cycle (Liu et al., Reference Liu2022). Variations in serum AMH levels are not only caused by differences in the number of follicles but also by genetic factors (Moolhuijsen et al., Reference Moolhuijsen2022). This could be due to the fact that in women with PCOS, the transcriptional regulation of AMH and its principal receptor AMHR2 is altered, triggering a prolongation and increase in their expression pattern (Moolhuijsen and Visser, Reference Moolhuijsen and Visser2020).

According to the knowledge obtained up to now on the relationship between AMH and PCOS, some authors assume that it is too early to use the serum levels of this hormone as a diagnosis criterion of PCOS (Moolhuijsen and Visser, Reference Moolhuijsen and Visser2020). However, other authors state that an elevated serum AMH level can be used as a predictor to reflect with certainty the diagnosis of PCOS among women of reproductive age, when studied together with the Rotterdam criteria (Butt et al., Reference Butt2022). Besides, the extragonadal effects of AMH recently discovered suggest that there could be crosstalk between the ovary, the placenta, and the brain, and that the contribution of AMH to the physiopathology of POS could be even more elaborate than was thought (Moolhuijsen and Visser, Reference Moolhuijsen and Visser2020). However, PCOS is a syndrome and, as such, no single diagnostic criteria are sufficient for clinical diagnosis (Butt et al., Reference Butt2022).

Tumours

Several studies carried out, both on women and on mares, have demonstrated that AMH is a good tumour biomarker, in addition to the inhibin B of granulosa cell tumours (GCT) (Bedenk et al., Reference Bedenk, Vrtačnik-Bokal and Virant-Klun2019). In both species, an increase in AMH serum concentrations has been observed, due to the enlargement of the granulosa cells that release into the bloodstream large amounts of this hormone (Bedenk et al., Reference Bedenk, Vrtačnik-Bokal and Virant-Klun2019). In women, the AMH serum concentrations increase to between 76% and 96% (Ball et al., Reference Ball2008; La Marca and Volpe, Reference La Marca and Volpe2007). In mares, the AMH concentrations rise until reaching a mean of 1,901.4–1,144.6 ng/mL (Claes and Ball, Reference Claes and Ball2016). Since the increase in the AMH concentration occurs in over 90% of GCT in women and mares, the measurement of this hormone is becoming the best GCT biomarker in both species (Ball et al., Reference Ball2008).

In mares, GCT are the most frequent type of tumour in ovaries (Almeida et al., Reference Almeida2011), representing 2.5% of all equine tumours (Behrendt et al., Reference Behrendt2021). They cause a prolonged anoestrus, stallion-like behaviour, or a persistent oestrus (Gharagozlou et al., Reference Gharagozlou2013) as well as a suppression of follicular activity. The latter triggers a diminution of the FSH concentration, thus producing atrophy of the oocytes during follicular development (Almeida et al., Reference Almeida2011) and an increase in LH concentration (Ball et al., Reference Ball2008). In the study carried out by Ball et al. (Reference Ball2008), they could see that, in addition to the increase in their AMH, 87% of the mares with GCT showed an increase in inhibin greater than 0.7 ng/ml. Also, 67% of them also gave an increase in testosterone greater than 0.045 ng/ml. Similar results were obtained in the study carried out by Almeida et al. (Reference Almeida2011), who obtained that 73% of the mares with GCT showed an increase in inhibin, and 45% of them also exhibited an increase in testosterone. Therefore, the diagnosis of GCT is more certain if AMH, testosterone, and inhibin levels are markedly increased and an abnormally enlarged ovary is present (Renaudin et al., Reference Renaudin2021). In addition, recently, increased levels of these hormones have been linked to stallion-like behaviour. However, no relationship has been found between these increases and other signs associated with GCT, such as aggression or persistent oestrus (Huggins et al., Reference Huggins2024). In fact, certain behavioural abnormalities can also occur in mares with healthy ovaries, although these could be due to early, clinically undetectable neoplastic changes in the ovaries (Wolf et al., Reference Wolf2024).

In the case of other types of cancer, it has been demonstrated that, for instance, women with lymphoma and leukaemia have a reduced concentration of AMH but it is not known whether their follicle density is also reduced (Liebenthron et al., Reference Liebenthron2019). In the recent work by Yoon et al. (Reference Yoon2020), they study the effect of endometrioma on the serum levels of AMH, in comparison with benign ovary cysts. They conclude that the amount of AMH does not present any statistically significant differences between the group of women with endometrioma and the group with cysts. However, the level of AMH in serum tended to show a positive relationship with the size of the endometrioma (Yoon et al., Reference Yoon2020). They also concluded that the impact on the physiological level of AMH of a benign ovarian cyst is a clinical problem with an indefinite conclusion (Yoon et al., Reference Yoon2020).

It has also been noted that, although cancer does not affect the reproductive system, treatment for it does affect reproductive life. Su et al. (Reference Su2020) showed that the AMH levels begin to decrease as the gonadotoxicity of the treatment increases (Su et al., Reference Su2020). They also reported that, during the first 2–3 years after the end of the treatment, the ovarian function recovers, although this may vary according to the age and the gonadotoxicity of the treatment (Su et al., Reference Su2020).