Anti-Müllerian Hormone Secretion Research Articles

From biological marker to clinical application: the role of anti-Müllerian hormone for delayed puberty and idiopathic non-obstructive azoospermia in males.

Role of anti-Müllerian hormone (AMH) in male development and fertility prediction. (A) AMH levels in normal development, constitutional delay of growth and puberty (CDGP) and central hypogonadotropic hypogonadism (CHH) models. In normal males, AMH declines with puberty; in CDGP and CHH, AMH is normal or slightly elevated or abnormally low, indicating delayed or impaired pubertal progression. (B) AMH as a predictor of successful sperm retrieval (SSR) in idiopathic non-obstructive azoospermia. Lower AMH levels (<2.6 ng/mL) correlate with higher SSR in microdissection testicular sperm extraction. Anti-Müllerian hormone (AMH), a biomarker secreted by Sertoli cells in the testes, has emerged as a critical indicator of male reproductive function with significant clinical application potential. AMH reflects Sertoli cell activity and plays a pivotal role across different stages of male gonadal function. First, in prepubertal males, AMH levels are crucial for assessing testicular development and the progression of puberty, with delayed or insufficient AMH secretion often being associated with disorders such as delayed puberty. Second, in reproductive-age males, AMH serves as an important biomarker for evaluating spermatogenic capacity, particularly in cases of idiopathic non-obstructive azoospermia. In these patients, AMH levels can help predict the success of testicular sperm extraction, thereby influencing fertility treatment strategies. This review explores the physiological mechanisms of AMH and its diagnostic and prognostic significance in both delayed puberty and fertility disorders in reproductive-age males. While AMH shows great promise in the management of hypogonadism, further research is needed to validate its clinical utility and refine treatment protocols for optimizing patient outcomes.

Physiological Anti-Müllerian Hormone Concentrations in Male and Female Dogs and Cats before and around Puberty.

In recent years several studies established the diagnostic value of anti-Müllerian hormone (AMH) in companion animals. However, less is known about physiological AMH concentrations in young individuals highlighting the necessity to apply the diagnostic findings to this group. The aim of this study was to determine the AMH values of healthy male and female dogs between the age of 8 and 48 weeks, tomcats under 8 weeks and up to 48 weeks of age and queens between 2 to 12 weeks of age. In total, 96 blood samples were collected. Anti-Müllerian hormone was measured in all samples and testosterone was measured in the oldest age group of the males in both species. The hormones were analyzed using a human based chemiluminescence immune assay. Overall, AMH concentrations were higher in males than in females (p < 0.001). According to the AMH concentration there was no difference in males, but queens had significant higher AMH concentrations than bitches (p < 0.001). AMH remained high in males up to week 24 and decreased significantly thereafter (tomcats: p = 0.015; male dogs: p = 0.013), which correlated with an increase in testosterone levels for male dogs only. In bitches, AMH remained below the detection limit until the week 16 and slightly increased subsequently. In queens, AMH was detectable from the beginning with a significant increase in the older age group (p = 0.003). Half of the cats in the older age group even approached the chemiluminescence immune assay's upper limit. The results show that female cats secrete AMH much earlier than female dogs in which AMH secretion begins just shortly before the start of the puberty. In the male animals, the decrease in AMH concentration around puberty was similar in dogs and cats, but a correlation with the increase of testosterone was only observed in dogs. Further research is required to determine the origin of the high AMH concentrations in female kittens and the lack of correlation between testosterone and AMH concentrations in male kittens.

Sexually dimorphic expression of AMH facilitates testis differentiation pathway in the tropical lizard, Calotes versicolor (Daud.)

The Anti-mullerian hormone (AMH), also known as Mullerian inhibiting substance (MIS), is a glycoprotein that belongs to transforming growth factor β superfamily. The significance of AMH during gonadal differentiation is not clearly deciphered in reptiles. Hence, current study aims to know the onset of AMH secretion and its functional role in Mullerian duct regression gonadal differentiation in tropical lizard, Calotes versicolor which exhibits a novel Female-Male-Female-Male (FMFM) pattern of temperature-dependent sex determination (TSD). The Immunohistochemistry and qRT-PCR techniques were employed to analyze the gonadal expression profile of AMH during different stages of embryonic development. The eggs of the lizard were incubated at both male-producing temperature (MPT: 25.5 ± 0.5 °C) and female-producing temperatures (FPT: 31.5 ± 0.5 °C). The results reveal that the onset of AMH gene expression was observed as early as oviposition prior to the immunolocalization of AMH protein at early-TSP (Temperature-sensitive period). The substantial rise in the intensity of the immunoreaction of AMH protein in the cytoplasm confining to Sertoli cells of seminiferous cords at MPT with low level of expression at FPT during gonadal sex differentiation, specify sexually dimorphic expression of AMH protein. Further, with the onset of sexual differentiation, the developing testis immensely expresses AMH gene which is 7-fold greater than that of transcripts levels in female embryos; signifies its conserved role in Mullerian duct regression thereby promoting testis differentiation. The robust immunnoexpression of AMH protein during post-gonadal differentiation coincides with the onset of the regression of Mullerian duct point out a positive correlation between testis differentiation and Mullerian duct regression, thus facilitating testis differentiation pathway. Based on the immunoexpression pattern of AMH protein and transcript levels of AMH gene, it is inferred that AMH plays a significant role in Mullerian duct regression, favoring testis differentiation.

Iron deposition in ovarian endometriosis evaluated by magnetic resonance imaging R2* correlates with ovarian function

Research questionDoes iron overload in patients with endometriosis affect ovarian function? Can a method be developed to visually reflect this? DesignMagnetic resonance imaging (MRI) R2* was used to evaluate the correlation between iron deposition of ovarian and anti-Müllerian hormone (AMH) in patients with endometriosis. All patients underwent T2* MRI scanning. Serum AMH levels were measured preoperatively. The area of focal iron deposition, iron content of the cystic fluid and AMH levels between the endometriosis and control groups were compared using non-parametric tests. The effects of iron overload on AMH secretion in mouse ovarian granulosa cells were investigated by adding different concentrations of ferric citrate to the medium. ResultsA significant difference was found between endometriosis and control groups in area of iron deposition (P < 0.0001), cystic fluid iron content (P < 0.0001), R2* of lesions (P < 0.0001) and R2* of the cystic fluid (P < 0.0001). Negative correlations were found between serum AMH levels and R2* of cystic lesions in patients with endometriosis aged 18–35 years (rs = –0.6484, P < 0.0001), and between serum AMH levels and R2* of cystic fluid (rs = –0.5074, P = 0.0050). Transcription level (P < 0.0005) and secretion level (P < 0.005) of AMH significantly decreased with the increase in iron exposure. ConclusionIron deposits can impair ovarian function, which is reflected in MRI R2*. Serum AMH levels and R2* of cystic lesions or fluid in patients aged 18–35 years had a negative correlation with endometriosis. R2* can be used to reflect the changes of ovarian function caused by iron deposition.

Functional analysis of rare anti-Müllerian hormone protein-altering variants identified in women with PCOS.

Recently, rare heterozygous AMH protein-altering variants were identified in women with polycystic ovary syndrome (PCOS), causing reduced anti-Müllerian hormone (AMH) signaling. However, the exact functional mechanism remains unknown. Here, we analyzed the processing, secretion, and signaling of these AMH variants. Functional analysis of six PCOS-specific AMH variants (V12G, P151S, P270S, P352S, P362S, H506Q) and one control-specific variant (A519V) was performed in the mouse granulosa cell-line KK-1. Human (h) AMH-151S and hAMH-506Q have ∼90% decreased AMH signaling compared to wild-type (wt) AMH signaling. Coexpression of hAMH-151S or hAMH-506Q with wt-hAMH dose-dependently inhibited wt-hAMH signaling. Western blotting revealed that hAMH-151S and hAMH-506Q proteins were detected in the cell lysate but not in the supernatant. Confocal microscopy showed that HEK293 cells expressing hAMH-151S and hAMH-506Q had higher cellular AMH protein levels with endoplasmic reticulum (ER) retention compared to cells expressing wt-hAMH. Using two AMH ELISA kits, hAMH-151S was detected in the cell lysate, while only very low levels were detected in the supernatant. Both hAMH-362S and hAMH-519V were detectable using the automated AMH ELISA but showed severely reduced immunoactivity in the manual ELISA. Surprisingly, hAMH-506Q was undetectable in both the cell lysate and supernatant using either ELISA. However, in PCOS cases, heterozygous carriers of the P151S and H506Q variants still had detectable AMH in both assays. Thus, P151S and H506Q disrupt normal processing and secretion of AMH, causing ER retention. Additionally, AMH variants can impair the AMH immunoactivity. An AMH variant may be considered when serum AMH levels are relatively low in PCOS cases.

Potential Role of Anti-Müllerian Hormone in Regulating Seasonal Reproduction in Animals: The Example of Males.

Seasonal reproduction is a survival strategy by which animals adapt to environmental changes to improve their fitness. Males are often characterized by a significantly reduced testicular volume, indicating that they are in an immature state. Although many hormones, including gonadotropins, have played a role in testicular development and spermatogenesis, research on other hormones is insufficient. The anti-Müllerian hormone (AMH), which is a hormone responsible for inducing the regression of Müllerian ducts involved in male sex differentiation, was discovered in 1953. Disorders in AMH secretion are the main biomarkers of gonadal dysplasia, indicating that it may play a crucial role in reproduction regulation. A recent study has found that the AMH protein is expressed at a high level during the non-breeding period of seasonal reproduction in animals, implying that it may play a role in restricting breeding activities. In this review, we summarize the research progress on the AMH gene expression, regulatory factors of the gene's expression, and its role in reproductive regulation. Using males as an example, we combined testicular regression and the regulatory pathway of seasonal reproduction and attempted to identify the potential relationship between AMH and seasonal reproduction, to broaden the physiological function of AMH in reproductive suppression, and to provide new ideas for understanding the regulatory pathway of seasonal reproduction.

Efficiency of immunocastration with an anti-gonadotropin-releasing hormone vaccine on cryptorchid bulls

Cryptorchid bulls have low economic value owing to the effects of masculinization. Moreover, surgical removal of an ectopic testis is difficult in certain clinical cases. Recently, immunocastration has garnered popularity as a nonsurgical castration method in pig farming; however, the effects of immunocastration on cryptorchid bulls are yet to be yet. Herein, we investigated endocrine changes due to immunocastration in cryptorchid bulls and studied its effectiveness. This study included 13 Holstein bulls diagnosed with cryptorchidism and classified into two groups based on pubertal period: <8 months of age (pregroup) and ≥8 months of age (postgroup). Antigonadotropin-releasing hormone (GnRH) vaccine was used for immunocastration, and two vaccine doses were administered. Blood testosterone and anti-Müllerian hormone (AMH) levels were measured and analyzed for endocrine evaluation. The testosterone levels significantly decreased following the start of immunocastration in both groups, thereby confirming the efficacy of antiGnRH vaccination in cryptorchid bulls. The AMH levels significantly increased in the pregroup with two antiGnRH vaccination, suggesting a compensatory response via the neutralization of GnRH antibodies. The AMH levels did not significantly change in the postgroup, indicating the partial suppression of AMH secretion in Sertoli cells during sexual maturation and failure of Sertoli cell maturation. Thus, we successfully restrained the serum testosterone levels in cryptorchid bulls using antiGnRH vaccine. The testosterone levels are a useful indicator of the immunocastration effect on cryptorchid bulls. Hereafter, a vaccine program that can sustain the castration effect on cryptorchid bulls is necessary.

Erxian decoction alleviates cisplatin-induced premature ovarian failure in rats by reducing oxidation levels in ovarian granulosa cells

Ethnopharmacological relevantErxian Decoction (EXD) has been used empirically for more than 70 years to treat premature ovarian failure (POF), but more research is needed to understand how it works. Aim of the researchThe study aims to ascertain both in vivo and in vitro rewards of EXD. Materials and methodsEXD is composed of Curculiginis Rhizoma, Epimedii Folium, Morindae Officinalis, Angelicae Sinensis, Anemarrhenae Rhizoma, and Phellodendri Chinensis Cortex. UPLC/MS analysis was used to investigate the components of EXD. Using a POF model created by administering cisplatin to rats intraperitoneally, the pharmacodynamic effects of EXD were investigated. Three dose groups of EXD were garaged into rats: high (15.6 g/kg), medium (7.8 g/kg), and low (3.9 g/kg). By using a vaginal smear, the impact of EXD on the rat estrous cycle was evaluated. An ELISA test was used to measure the anti-Mullerian hormone (AMH), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels in the serum of rats. By using HE stains, pathological alterations in the ovaries may be seen. MDA and SOD levels in ovarian samples were used to measure the degree of ovarian oxidation. TUNEL labeling of ovarian sections was used to find apoptosis levels. By using ATP, energy production was evaluated. The relative expression of proteins connected to aging and the RAGE pathway was assessed using Western blot. Then, using H2O2, a model of senescent human ovarian granulosa cells (KGN) was created in vitro. The impact of EXD and H2O2 on cellular senescence was discovered using-galactosidase staining. Cell apoptosis levels were found using PI/Hoechest33342. By using DCFH-DA, intracellular ROS was examined. MDA and SOD concentrations were used to measure the degree of cellular oxidation. RAGE-related mRNA and protein expression were evaluated using RT-qPCR and western blotting. ResultsUsing UPLC/MS analysis, 39 chemicals in EXD were found. Rats' estrous cycles were enhanced by EXD, which increased ovarian index and follicle count and reduced the proportion of atretic follicles in the rats. EXD reduced LH and FSH output while restoring AMH and E2 secretion. In ovarian tissues, EXD reduced the amount of apoptosis and MDA while raising SOD activity and ATP levels. The protein levels of p16, p21, p53, and Lamin A/C were among the senescence-related proteins that EXD lowered, along with the levels of RAGE, PI3K, BAX, and CASPASE 3. Anti-apoptotic protein BCL-2 was also raised in the RAGE pathway. Senescence, apoptosis, ROS, and MDA levels in the KGN cells were lowered in vitro by EXD. Additionally, EXD increased the anti-apoptotic potential by changing the expression of CAT, SOD2, and SIRT1. RAGE, BAX, BCL-2, CASPASE 3, and p38 expression levels were altered by EXD, enhancing its anti-apoptotic capability. ConclusionEXD boosted the ovary's antioxidant and anti-apoptotic capabilities while enhancing the estrous cycle and hormone output. These findings strongly suggested that EXD may contribute to the alleviation of POF and ovarian granulosa cells senescence.

BMP6 regulates AMH expression via SMAD1/5/8 in goat ovarian granulosa cells

Anti-Müllerian hormone (AMH) is produced by ovarian granulosa cells (GCs)and plays a major role in inhibiting the recruitment of primordial follicles and reducing the sensitivity of growing follicles to follicle-stimulating hormone (FSH). Bone morphogenetic protein 6 (BMP6) has similar spatiotemporal expression to AMH during follicular development, suggesting that BMP6 may regulate AMH expression. However, the specific mechanism by which BMP6 regulates AMH expression remains unclear. The objectives of this study were to examine the molecular pathway by which BMP6 regulates AMH expression. The results showed that BMP6 promoted the secretion and expression of AMH in goat ovarian GCs. Mechanistically, BMP6 upregulated the expression of sex-determining region Y-box 9 (SOX9) and GATA-binding factor 4 (GATA4), which was associated with the transcriptional initiation of AMH. AMH expression was significantly decreased by GATA4 knockdown. Moreover, BMP6 treatment promoted the phosphorylation of SMAD1/5/8, whereas inhibiting the SMAD1/5/8 signaling pathway significantly abolished BMP6-induced upregulation of AMH and GATA4 expression. Interestingly, the activation of SMAD1/5/8 alone did not affect the expression of AMH or GATA4. The results suggested that BMP6 upregulated GATA4 through the SMAD1/5/8 signaling pathway, which in turn promoted AMH expression.

Physiological role and diagnostic value of anti-Mullerian hormone in pediatrics

Background. Anti-Mullerian hormone (AMH) has now gained popularity as a marker of ovarian reserve. It is important to determine the place and role of AMH in children. The purpose of this work was to analyze the data of the scientific literature on the role of AMH in pediatric practice. Materials and methods. A review of the literature in PubMed was conducted, limiting itself to articles in English and updating the search in February 2022. The search term was “anti-Mullerian hormone”. A total of 437 manuscripts were found, including 37 review articles. The search was gradually narrowed with filters of clinical trials and systematic reviews to 75 articles. The references of the original and review articles were then checked to ensure a complete review. AMH is responsible for the differentiation of the gonads, provokes the regression of Mullerian ducts in the male fetus, correlates with karyotype, sexual development, levels of luteinizing hormone, follicle-stimulating hormone, and its serum levels reflect the ovarian reserve in women, even in childhood. Serum AMH is high from prenatal life to puberty. In postnatal period, the secretion of AMH by the testes is stimulated by follicle-stimulating hormone and strongly inhibited by androgens. AMH is of clinical value as a marker of testicular tissue in men with differences in sexual development and cryptorchidism, as well as in the assessment of persistent Mullerian duct syndrome. Determination of AMH is useful for assessing the function of the gonads without the need for stimulation tests and guides the etiological diagnosis of childhood male hypogonadism. In women, AMH is used as a prognostic marker of ovarian reserve and fertility. The use of criteria developed for adult women is problematic for adolescent girls, as clinical signs associated with polycystic ovary syndrome are normal phenomena of puberty. AMH can be used as an additional criterion in the diagnosis of polycystic ovary syndrome in adolescents. However, the lack of an international standard for AMH limits comparisons between AMH analyzes. Conclusions. AMH has broad clinical diagnostic utility in pediatrics, but interpretation is often complex and should be made in the context of not only the age and sex, but also the stage of development and puberty of the child. Recognition of the role of AMH beyond the development and maturation of the gonads may lead to new diagnostic and therapeutic applications that will further expand its use in pediatric practice.

AMH Regulation by Steroids in the Mammalian Testis: Underlying Mechanisms and Clinical Implications.

Anti-Müllerian hormone (AMH) is a distinctive biomarker of the immature Sertoli cell. AMH expression, triggered by specific transcription factors upon fetal Sertoli cells differentiation independently of gonadotropins or sex steroids, drives Müllerian duct regression in the male, preventing the development of the uterus and Fallopian tubes. AMH continues to be highly expressed by Sertoli until the onset of puberty, when it is downregulated to low adult levels. FSH increases testicular AMH output by promoting immature Sertoli cell proliferation and individual cell expression. AMH secretion also showcases a differential regulation exerted by intratesticular levels of androgens and estrogens. In the fetus and the newborn, Sertoli cells do not express the androgen receptor, and the high androgen concentrations do not affect AMH expression. Conversely, estrogens can stimulate AMH production because estrogen receptors are present in Sertoli cells and aromatase is stimulated by FSH. During childhood, sex steroids levels are very low and do not play a physiological role on AMH production. However, hyperestrogenic states upregulate AMH expression. During puberty, testosterone inhibition of AMH expression overrides stimulation by estrogens and FSH. The direct effects of sex steroids on AMH transcription are mediated by androgen receptor and estrogen receptor α action on AMH promoter sequences. A modest estrogen action is also mediated by the membrane G-coupled estrogen receptor GPER. The understanding of these complex regulatory mechanisms helps in the interpretation of serum AMH levels found in physiological or pathological conditions, which underscores the importance of serum AMH as a biomarker of intratesticular steroid concentrations.

Interpretation and significance of the definition of anti-Mullerian hormone in the practice of juvenile gynaecologist

The article presents an overview of the physiological role of anti-Mullerian hormone (AMH) during persons lifetime, the fluctuations of its values from birth to the reproductive period in women, the significance of its determination in the diagnosis and prognosis of treatment outcomes for many gynecological diseases. AMH is produced mainly by preantral and early antral follicles and decreases during the final maturation and luteinization. AMH plays a potential role in preserving the ovarian reserve by performing dual actions. AMH inhibits the initial recruitment of follicles, preventing the influence of stimulating growth factors for recruitment (KIT-ligand, the main fibroblast growth factor). From the moment of puberty, AMH reduces the sensitivity of primary follicles to the follicle-stimulating hormone, reducing the likelihood of their cyclic recruitment. The systematic review data presented the characteristics of the ovarian reserve in a healthy female population aged 0 to 19 years. At birth, very low AMH values were noted with an increase in its level in the first 3 months of life, followed by a monthly increase of 31%. A significant increase in AMH secretion was revealed by the beginning of puberty, then most authors noted a constant level of serum AMH in the adolescent period. The level of AMH in the blood serum decreases with an increase in chronological age by 68% annually and varies during the menstrual cycle. AMH is an important diagnostic tool in pediatric practice when differentiating various causes of puberty disorders, virilization and menstrual cycle disorders in girls.

The effect of GnRH stimulation on AMH regulation in central precocious puberty and isolated premature thelarche.

There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups. Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group. After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group's basal AMH level; AMH response to GnRH stimulation was not different (p>0.05). In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.

Serum anti-Müllerian hormone levels in women are unstable in the postpartum period but return to normal within 5 months: a longitudinal study

Anti-Müllerian hormone (AMH) levels fall during pregnancy but the amount of time required for AMH levels to return to normal has not been accurately determined. We have previously shown that AMH levels have yet to return to normal in some women at 3-months postpartum. In this study, AMH levels were examined at 1- and 5-months postpartum to examine whether AMH levels had returned to normal within this interval. Longitudinal study involving 38 pregnant women, with serum samples taken in the first trimester, third trimester, 1-month postpartum, 5-months postpartum and 4-6 years postpartum. Participants were recruited from a tertiary maternity clinic (single centre). All women in the study were intending to breastfeed exclusively for at least 5 months, with all 38 participants achieving this at 1-month postpartum and 36/38 after 5 months. Serum AMH concentrations had not returned to expected non-pregnant levels by 1-month postpartum. At 5-months postpartum, mean AMH concentrations were similar to expected non-pregnant levels but the rank order of AMH concentrations was still dissimilar to the non-pregnant state. The regulation of AMH secretion appears to be distinctly different in non-pregnant, pregnant and postpartum populations. This may affect the conclusions that can be drawn from AMH measurements in women during pregnancy and the postpartum period.

Anti-Müllerian hormone (AMH) concentrations are maximal at puberty in male donkeys and secretion is redirected from the blood stream to seminal plasma

Sertoli cells produce anti-Müllerian hormone (AMH) and number of these cells is associated with numbers of sperm produced. The study aim was to quantify AMH concentrations in serum and seminal plasma of donkeys during puberty, and to correlate the values with those for testicular width and semen quality of sexually mature males. Blood was collected from five donkeys every second month from 4 to 24 months of age, and then once at 40 months of age. Semen was collected once monthly, from 13 to 19 and 23–25 months of age. There was quantification of AMH concentrations in serum and seminal plasma. During puberty, there was a redirection of AMH secretion from the blood stream into seminal plasma. In serum, AMH concentrations increased during puberty with a maximal concentration at 16 months and the changes were similar for seminal plasma with a maximal concentration at 18 months of age. Serum AMH concentrations from 14–20 were greater than at 12 or 22 months of age. Maximal serum AMH concentrations were associated with testicular width at 24 months (r = 0.97, P = 0.005), but not with sperm count, sperm motility or percentage of sperm with normal morphology at 42 months of age. There were no significant correlations among values for AMH concentrations in seminal plasma during puberty and values for any of the seminal variables.

Male Hypogonadism and Disorders of Sex Development.

Disorders of Sex Development (DSD) are congenital anomalies in which there is a discordance between chromosomal, genetic, gonadal, and/or internal/external genital sex. In XY individuals, the process of fetal sex differentiation can be disrupted at the stage of gonadal differentiation, resulting in gonadal dysgenesis, a form of early fetal-onset primary hypogonadism characterized by insufficient androgen and anti-Müllerian hormone (AMH) production, which leads to the development of ambiguous or female genitalia. The process of sex differentiation can also be disrupted at the stage of genital differentiation, due to isolated defects in androgen or AMH secretion, but not both. These are forms of fetal-onset hypogonadism with dissociated gonadal dysfunction. In this review, we present a perspective on impaired testicular endocrine function, i.e., fetal-onset male hypogonadism, resulting in incomplete virilization at birth.

Anti-Müllerian hormone in managed African and Asian rhino species

Serum collected across the lifespan of four managed rhino species: black (Diceros bicornis, n = 16), white (Ceratotherium simum simum, n = 19), greater one-horned (GOH, Rhinoceros unicornis, n = 11) and Sumatran (Dicerorhinus sumatrensis, n = 6) were validated and analyzed in an anti-Müllerian hormone (AMH) enzyme- linked immunoassay. Concentrations of AMH were examined over time, between sexes and throughout different reproductive states which included n = 3 female white rhinos immunocontracepted with porcine zona pellucida (pZP). Across species, males produced higher AMH concentrations compared to females. Among males, AMH concentrations varied by species aside from comparable values secreted between black and white rhinos. The GOH and Sumatran rhino secreted the highest and lowest male AMH concentrations, respectively. However, within each species, AMH concentrations were similar across male age categories. Preliminary insight into male AMH changes from birth to sexual maturity suggest its potential as a marker for onset of testicular maturation. Female black, GOH and Sumatran rhinos secreted comparable AMH concentrations which were higher than those in white rhino. Within each species, inter-individual variation in AMH secretion occurred among females of similar age. While AMH secretion did not differ across the ages sampled for female white (4->26 yr) and GOH (4–26 yr) rhinos, black and Sumatran rhinos >26 and <4 yr, respectively secreted lower AMH compared to conspecific females 7–26 yr of age. Two idiopathic infertility cases corresponded to low (outside species range) AMH values. The establishment of normative AMH concentrations in managed African and Asian rhinos provides an additional metric beyond traditional sex steroids to assess gonadal function. Further work is needed to determine if AMH can predict fertility potential in rhinos.

Discovery of new receptors regulating luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs to explore a new paradigm for mechanisms regulating reproduction

Previous studies in the 1960s and 1970s have reported that both gonadotropin-releasing hormone (GnRH) and estradiol-activated nuclear estrogen receptors regulate gonadotropin secretion in women. However, I had previously reported that gonadotroph function is regulated by complex crosstalk between several membrane receptors. RNA-seq had previously revealed 259 different receptor genes expressed in the anterior pituitary of heifers. However, the biological roles of most of these receptors remain unknown. I identified four new receptors of interest: G protein-coupled receptor 30 (GPR30), anti-Mullerian hormone (AMH) receptor type 2 (AMHR2), and G protein-coupled receptors 61 and 153 (GPR61 and GPR153). GPR30 rapidly (within a few minutes) mediates picomolar, but not nanomolar, levels of estradiol to suppress GnRH-induced luteinizing hormone (LH) secretion from bovine gonadotrophs, without decreasing mRNA expressions of the LHα, LHβ, or follicle-stimulating hormone (FSH) β subunits. GPR30 is activated by other endogenous estrogens, estrone and estriol. Moreover, GPR30 activation by zearalenone, a nonsteroidal mycoestrogen, suppresses LH secretion. AMHR2, activated by AMH, stimulates LH and FSH secretion, thus regulating gonadotrophs, where other TGF-β family members, including inhibin and activin, potentially affect FSH secretion. I also show that GPR61, activated by its ligand (recently discovered) significantly alters LH and FSH secretion. GPR61, GPR153, and AMHR2 co-localize with the GnRH receptor in unevenly dispersed areas of the bovine gonadotroph cell surface, probably lipid rafts. The findings summarized in this review reveal a new paradigm regarding the mechanisms regulating reproduction via novel receptors expressed on bovine gonadotrophs.

Serum anti-Müllerian hormone levels during estrus and diestrus in mares

Anti-Müllerian hormone (AMH) is a homodimeric glycoprotin secreted by granulosa cells in postnatal females. AMH plays an important role in follicle recruitment. The aim of the study was to analyse AMH concentrations under the guidance of circulating estradiol and progesterone levels in mares. The study was conducted on 25 non-lactating mares with regular estrous cycles. Blood samples were collected during estrus and diestrus to analyse estradiol, progesterone and AMH concentrations. Estradiol and progesterone concentrations were significantly different (P &lt; 0.001) between estrus and diestrus. AMH concentrations in estrus were significantly higher than those in diestrus (P &lt; 0.05). According to the authors’ knowledge, this is the first report to suggest that the sexual cycle stage affects AMH concentrations in mares. Further investigations are needed to reveal factors affecting the AMH production and secretion pattern throughout the sexual cycle.

Contribution of recruitable follicles to circulating anti-Müllerian hormone levels following maximal gonadotrophin stimulation in patients with limited ovarian reserve

In women, the majority of anti-Müllerian hormone (AMH) measured in serum originate from small antral follicles measuring 2–10 mm. In gonadotrophin-stimulated cycles prior to assisted reproductive technology (ART), most of the recruitable follicles develop beyond 10 mm in size and thus lose their AMH secretion capacity causing declining serum AMH levels. The aim of this study was to define the residual serum AMH level after elimination of the AMH producing recruitable follicles following maximal gonadotrophin stimulation. We measured serum AMH and number of follicles according to size at several time points during a cycle of maximal gonadotrophin stimulation (fixed dose of 300 IE HP-hMG) in 107 women with low AMH (median AMH 5 pmol/L, interquartile range (IQR) 3.3–8.3). We found that AMH decreased gradually and reached a minimum level of −55.4% (95% CI −59.6; −50.7) of the baseline value four days after ovulation trigger. Our findings suggest that the residual AMH production origins from pre-antral and small antral follicles not visible by sonography and that they account for up to 40% of the circulating AMH.