Dataset Information

Hypothalamic neuroglial plasticity is regulated by anti-Mullerian hormone and disrupted in polycystic ovary syndrome.

ABSTRACT:

Background

Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder affecting between 5 and 18% of women worldwide. An elevated frequency of pulsatile luteinizing hormone (LH) secretion and higher serum levels of anti-Müllerian hormone (AMH) are frequently observed in women with PCOS. The origin of these abnormalities is, however, not well understood.

Methods

We studied brain structure and function in women with and without PCOS using proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging combined with fiber tractography. Then, using a mouse model of PCOS, we investigated by electron microscopy whether AMH played a role on the regulation of hypothalamic structural plasticity.

Findings

Increased AMH serum levels are associated with increased hypothalamic activity/axonal-glial signalling in PCOS patients. Furthermore, we demonstrate that AMH promotes profound micro-structural changes in the murine hypothalamic median eminence (ME), creating a permissive environment for GnRH secretion. These include the retraction of the processes of specialized AMH-sensitive ependymo-glial cells called tanycytes, allowing more GnRH neuron terminals to approach ME blood capillaries both during the run-up to ovulation and in a mouse model of PCOS.

Interpretation

We uncovered a central function for AMH in the regulation of fertility by remodeling GnRH terminals and their tanycytic sheaths, and provided insights into the pivotal role of the brain in the establishment and maintenance of neuroendocrine dysfunction in PCOS.

Funding

INSERM (U1172), European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement n° 725149), CHU de Lille, France (Bonus H).

SUBMITTER: Barbotin AL

PROVIDER: S-EPMC10070524 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hypothalamic neuroglial plasticity is regulated by anti-Müllerian hormone and disrupted in polycystic ovary syndrome.

Barbotin Anne-Laure AL Mimouni Nour El Houda NEH Kuchcinski Grégory G Lopes Renaud R Viard Romain R Rasika Sowmyalakshmi S Mazur Daniele D Silva Mauro S B MSB Simon Virginie V Boursier Angèle A Pruvo Jean-Pierre JP Yu Qiang Q Candlish Michael M Boehm Ulrich U Bello Federica Dal FD Medana Claudio C Pigny Pascal P Dewailly Didier D Prevot Vincent V Catteau-Jonard Sophie S Giacobini Paolo P

EBioMedicine 20230329

<h4>Background</h4>Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder affecting between 5 and 18% of women worldwide. An elevated frequency of pulsatile luteinizing hormone (LH) secretion and higher serum levels of anti-Müllerian hormone (AMH) are frequently observed in women with PCOS. The origin of these abnormalities is, however, not well understood.<h4>Methods</h4>We studied brain structure and function in women with and without PCOS using proton magnetic res ...[more]

PMID: 37001236

Similar Datasets

Project description:BackgroundThe majority of available studies on the AMH thresholds were not age-specific and performed the receiver operating characteristic curve (ROC) analysis, based on variations in sensitivity and specificity rather than positive and negative predictive values (PPV and NPV, respectively), which are more clinically applicable. Moreover, all of these studies used a pre-specified age categorization to report the age-specific cut-off values of AMH.MethodsA total of 803 women, including 303 PCOS patients and 500 eumenorrheic non-hirsute control women, were enrolled in the present study. The PCOS group included PCOS women, aged 20-40 years, who were referred to the Reproductive Endocrinology Research Center, Tehran, Iran. The Rotterdam consensus criteria were used for diagnosis of PCOS. The control group was selected among women, aged 20-40 years, who participated in Tehran Lipid and Glucose cohort Study (TLGS). Generalized additive models (GAMs) were used to identify the optimal cut-off points for various age categories. The cut-off levels of AMH in different age categories were estimated, using the Bayesian method.Main results and the role of chanceTwo optimal cut-off levels of AMH (ng/ml) were identified at the age of 27 and 35 years, based on GAMs. The cut-off levels for the prediction of PCOS in the age categories of 20-27, 27-35, and 35-40 years were 5.7 (95 % CI: 5.48-6.19), 4.55 (95 % CI: 4.52-4.64), and 3.72 (95 % CI: 3.55-3.80), respectively. Based on the Bayesian method, the PPV and NPV of these cut-off levels were as follows: PPV = 0.98 (95 % CI: 0.96-0.99) and NPV = 0.40 (95 % CI: 0.30-0.51) for the age group of 20-27 years; PPV = 0.96 (95 % CI: 0.91-0.99) and NPV = 0.82 (95 % CI: 0.78-0.86) for the age group of 27-35 years; and PPV = 0.86 (95 % CI: 0.80-0.94) and NPV = 0.96 (95 % CI: 0.93-0.98) for the age group of 35-40 years.ConclusionsApplication of age-specific cut-off levels of AMH, according to the GAMs and Bayesian method, could elegantly assess the value of AMH in discriminating PCOS patients in all age categories.