Anti-Mullerian hormone (AMH), also called Mullerian inhibiting substance, was shown to be synthesized by the ovary in the eighties. This article reviews the main findings of the past 20 years on the regulation of the expression of AMH and its specific receptor AMHR2 by granulosa cells, the mechanism of action of AMH, the different roles it plays in the reproductive organs, its clinical utility and its involvement in the principal pathological conditions affecting women. The findings in respect of regulation tell us that AMH and AMHR2 expression is mainly regulated by Bone Morphogenetic Proteins, gonadotropins and estrogens. It has now been established that AMH regulates the different steps of folliculogenesis and that it has neuroendocrine effects. On the other hand, the importance of serum AMH as a reliable marker of ovarian reserve and as a useful tool in the prediction of the polycystic ovary syndrome (PCOS) and primary ovarian failure has also been acknowledged. Last but not least, a large body of evidence points to the involvement of AMH in the pathogenesis of PCOS.

Anti-Müllerian Hormone in Female Reproduction.

Huangqin decoction ameliorates DSS-induced ulcerative colitis: Role of gut microbiota and amino acid metabolism, mTOR pathway and intestinal epithelial barrier.

Diabetes is a major risk factor for cardiovascular diseases, including diabetic cardiomyopathy, atherosclerosis, myocardial infarction, and heart failure. As cardiovascular disease represents the number one cause of death in people with diabetes, there has been a major emphasis on understanding the mechanisms by which diabetes promotes cardiovascular disease, and how antidiabetic therapies impact diabetic heart disease. With a wide array of models to study diabetes (both type 1 and type 2), the field has made major progress in answering these questions. However, each model has its own inherent limitations. Therefore, the purpose of this guidelines document is to provide the field with information on which aspects of cardiovascular disease in the human diabetic population are most accurately reproduced by the available models. This review aims to emphasize the advantages and disadvantages of each model, and to highlight the practical challenges and technical considerations involved. We will review the preclinical animal models of diabetes (based on their method of induction), appraise models of diabetes-related atherosclerosis and heart failure, and discuss in vitro models of diabetic heart disease. These guidelines will allow researchers to select the appropriate model of diabetic heart disease, depending on the specific research question being addressed.

Guidelines on models of diabetic heart disease

Although there are large differences between horses and humans for reproductive anatomy, follicular dynamics, mono-ovulation, and embryo development kinetics until the blastocyst stage are similar. In contrast to humans, however, horses are seasonal animals and do not have a menstrual cycle. Moreover, horse implantation takes place 30 days later than in humans. In terms of artificial reproduction techniques (ART), oocytes are generally matured in vitro in horses because ovarian stimulation remains inefficient. This allows the collection of oocytes without hormonal treatments. In humans, in vivo matured oocytes are collected after ovarian stimulation. Subsequently, only intra-cytoplasmic sperm injection (ICSI) is performed in horses to produce embryos, whereas both in vitro fertilization and ICSI are applied in humans. Embryos are transferred only as blastocysts in horses. In contrast, four cells to blastocyst stage embryos are transferred in humans. Embryo and oocyte cryopreservation has been mastered in humans, but not completely in horses. Finally, both species share infertility concerns due to ageing and obesity. Thus, reciprocal knowledge could be gained through the comparative study of ART and infertility treatments both in woman and mare, even though the horse could not be used as a single model for human ART.

https://www.mdpi.com/2076-2615/11/8/2304/pdf

The Mare: A Pertinent Model for Human Assisted Reproductive Technologies?

Polycystic ovary syndrome (PCOS) is a common endocrine disease regulated by metabolic disorders, the effective intervention of which depends on diverse phenotypes (e.g., insulin resistance). Serum metabolic fingerprint (SMF) holds promise in characterizing the pathogenesis stress related to diseases; yet, PCOS diagnosis and phenotyping are time‐consuming and challenging due to the lack of an integrated metabolic tool. Here, a nanoparticle‐enhanced laser desorption/ionization mass spectrometry platform is introduced for one‐time serum metabolic fingerprinting and to identify the metabolic heterogeneity associated with obesity in PCOS patients. A decision tree based on the acquired SMFs is constructed, and real‐world simulations on independent internal and external cohorts are performed. The decision tree yields the area under the receiver operating characteristic curves (AUC) of 0.967 for PCOS diagnosis and AUC of 0.898 for phenotyping, respectively. The technical robustness of the “one‐stop shop” decision tree across laboratories is validated for clinical utility. The decision tree aims to improve PCOS management in comparison to clinical assessment, leading to a potential reduction in multiple blood tests and physician workload.

A “One‐Stop Shop” Decision Tree for Diagnosing and Phenotyping Polycystic Ovarian Syndrome on Serum Metabolic Fingerprints

Polycystic ovary syndrome (PCOS) is characterized by an oligo-anovulation, hyperandrogenism and polycystic ovarian morphology combined with major metabolic disturbances. However, despite the high prevalence and the human and economic consequences of this syndrome, its etiology remains unknown. In this study, we show that female Goto-Kakizaki (GK) rats, a type 2 diabetes mellitus model, encapsulate naturally all the reproductive and metabolic hallmarks of lean women with PCOS at puberty and in adulthood. The analysis of their gestation and of their fetuses demonstrates that this PCOS-like phenotype is developmentally programmed. GK rats also develop features of ovarian hyperstimulation syndrome. Lastly, a comparison between GK rats and a cohort of women with PCOS reveals a similar reproductive signature. Thus, this spontaneous rodent model of PCOS represents an original tool for the identification of the mechanisms involved in its pathogenesis and for the development of novel strategies for its treatment.

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Camille Gauthier

Papers

The Goto-Kakizaki rat is a spontaneous prototypical rodent model of polycystic ovary syndrome.

Découverte du premier modèle pré-clinique développant spontanément un syndrome des ovaires polykystiques