The Role of Anti-Müllerian Hormone in Ovarian Function

Anti-Müllerian hormone (AMH) is a member of the transforming growth factor β (TGFβ) superfamily, whose actions are restricted to the endocrine-reproductive system. Initially known for its role in male sex differentiation, AMH plays a role in the ovary, acting as a gatekeeper in folliculogenesis by regulating the rate of recruitment and growth of follicles. In the ovary, AMH is predominantly expressed by granulosa cells of preantral and antral follicles (i.e., post primordial follicle recruitment and prior to follicle-stimulating hormone (FSH) selection). AMH signals through a BMP-like signaling pathway in a manner distinct from other TGFβ family members. In this review, the latest insights in AMH processing, signaling, its regulation of spatial and temporal expression pattern, and functioning in folliculogenesis are summarized. In addition, effects of AMH variants on ovarian function are reviewed.</p

AMH in PCOS: Controlling the ovary, placenta, or brain?

Polycystic ovary syndrome (PCOS) is a very heterogeneous disease of which the exact pathophysiological mechanisms remain unknown. In PCOS, serum anti-Müllerian hormone (AMH) levels are significantly increased. AMH is a member of the transforming growth factor β family and is expressed by growing follicles in the ovaries. In PCOS, the transcriptional regulation of AMH and AMHR2 is altered, increasing and prolonging its temporal expression pattern. Moreover, the recently discovered extragonadal effects of AMH suggest that there might be a crosstalk between the ovary–placenta–brain. This review summarizes the recent findings concerning AMH and its role in the etiology of PCOS

AMH and AMHR2 Involvement in Congenital Disorders of Sex Development

Anti-Müllerian hormone (AMH) is one of the two testicular hormones involved in male development of the genitalia during fetal life. When the testes differentiate, AMH is secreted by Sertoli cells and binds to its specific receptor type II (AMHR2) on the Müllerian ducts, inducing their regression. In the female fetus, the lack of AMH allows the Müllerian ducts to form the Fallopian tubes, the uterus and the upper part of the vagina. The human AMH gene maps on 19p13.3 and consists of 5 exons and 4 introns spanning 2764 bp. The AMHR2 gene maps on 12q13.13, consists of 11 exons and is 7817-bp long. Defects in the AMH pathway are the underlying aetiology of a subgroup of disorders of sex development (DSD) in 46,XY patients. The condition is known as the persistent Müllerian ducts syndrome (PMDS), characterised by the existence of a uterus and Fallopian tubes in a boy with normally virilised external genitalia. Approximately 200 cases of patients with PMDS have been reported to date with clinical, biochemical and molecular genetic characterisation. An updated review is provided in this paper. With highly sensitive techniques AMH and AMHR2 expression has also been detected In other tissues, and massive sequencing technologies have unveiled variants in AMH and AMHR2 genes in hitherto unsuspected conditions.Fil: Brunello, Franco Gino. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentin

Polycystic ovary syndrome (PCOS): progress towards a better understanding and treatment of the syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. It has a strong hereditary component estimated at 60 to 70% in daughters. It has been suggested that environmental factors during the fetal period may be involved in the development of the syndrome in adulthood. However, the underlying mechanisms of its transmission remain unknown, thus limiting the development of effective therapeutic strategies.This article highlights how an altered fetal environment (prenatal exposure to high levels of anti-Müllerian hormone) can contribute to the onset of PCOS in adulthood and lead to the transgenerational transmission of neuroendocrine and metabolic traits through alterations in the DNA methylation process.The originality of the translational findings summarized here involves the identification of potential biomarkers for early diagnosis of the syndrome, in addition to the validation of a promising therapeutic avenue in a preclinical model of PCOS, which can improve the management of patients suffering from the syndrome

DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease.

DAX-1 (NR0B1) and SF-1 (NR5A1) are two nuclear receptor transcription factors that play a key role in human adrenal and reproductive development. Loss of DAX-1 function is classically associated with X-linked adrenal hypoplasia congenita. This condition typically affects boys and presents as primary adrenal insufficiency in early infancy or childhood, hypogonadotropic hypogonadism at puberty and impaired spermatogenesis. Late onset forms of this condition and variant phenotypes are increasingly recognized. In contrast, disruption of SF-1 only rarely causes adrenal insufficiency, usually in combination with testicular dysgenesis. Variants in SF-1/NR5A1 more commonly cause a spectrum of reproductive phenotypes ranging from 46,XY DSD (partial testicular dysgenesis or reduced androgen production) and hypospadias to male factor infertility or primary ovarian insufficiency. Making a specific diagnosis of DAX-1 or SF-1 associated conditions is important for long-term monitoring of endocrine and reproductive function, appropriate genetic counselling for family members, and for providing appropriate informed support for young people

Genetics and Epigenetics of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrinological and reproductive disorders in women of reproductive age with a global prevalence rate of 5–20%. It is a clinically and genetically heterogeneous disorder. There have been multiple reports from independent research groups from different ethnicities that a variety of factors, including genetics and epigenetics, significantly contribute to the etiopathogenesis of PCOS. GWAS, twin studies, and genotype-phenotype association studies have resulted in the identification of more than a dozen candidate genes/loci with PCOS. In the proposed book chapter, we aim to provide insight and discuss the role of various genetic and epigenetic elements that are responsible for PCOS globally and in India. This book chapter should serve as a reference to all the basic researchers and healthcare professionals on the genetics and epigenetics of PCOS