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Background Testicular sperm extraction (TESE) is the method of choice for recovering spermatozoa in patients with azoospermia. However, the lack of reliable biomarkers makes it impossible to predict sperm retrieval outcomes at TESE. To date, little attention has been given to anti-Müllerian hormone (AMH) serum levels in adult men with altered spermatogenesis. In this study we aimed to investigate whether serum concentrations of AMH and the AMH to total testosterone ratio (AMH/T) might be predictive factors for sperm retrieval outcomes during TESE in a cohort of 155 adult Caucasian men with azoospermia. Results AMH serum levels were significantly lower in nonobstructive azoospermia (NOA) that was unexplained, cryptorchidism-related, cytotoxic and genetic (medians [pmol/l] = 30.1; 21.8; 26.7; 7.3; and p = 0.02; 0.001; 0.04; <0.0001, respectively]) compared with obstructive azoospermia (OA) (median = 44.8 pmol/l). Lowest values were observed in cases of genetic NOA (p < 0.0001, compared with unexplained NOA) and especially in individuals with non-mosaic Klinefelter syndrome (median = 2.3 pmol/l, p <0.0001). Medians of AMH/T values were significantly lower in genetic NOA compared to unexplained, cryptorchidism-related NOA as well as OA. Only serum concentrations of AMH differed significantly between positive and negative groups in men with non-mosaic Klinefelter syndrome. The optimal cut-off of serum AMH was set at 2.5 pmol/l. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off to predict negative outcomes of SR were 100 %, 76.9 %, 66.6 %, 100 and 84.2 %, respectively. Conclusions Serum AMH levels, but not AMH/T values, are a good marker for Sertoli and germ cell population dysfunction in adult Caucasian men with non-mosaic Klinefelter syndrome and could help us to predict negative outcomes of SR at TESE with 100 % sensitivity when serum levels of AMH are below 2.5 pmol/l.

Background Few studies to date have attempted to measure serum anti-Müllerian hormone (AMH) levels in adult men, and solid references ranges have not yet been defined on a large cohort. Objective In this study, we aimed to first establish the reference ranges for serum AMH and AMH-to-total testosterone ratio (AMH/tT) in adult males. Secondly, we investigated the relationship between serum AMH and both reproductive hormones and semen parameters. Methods This single-center retrospective study included 578 normozoospermic adult men. Serum AMH concentrations were determined with an automated sandwich chemiluminescent immunoassay. Results The median serum AMH was 43.5 pmol/l. The 2.5th and 97.5th percentile values for serum AMH and AMH/tT were 16.4 pmol/l – 90.3 pmol/l, and 0.45 – 3.43, respectively. AMH was positively correlated with inhibin B and sperm concentration, and negatively correlated with age, FSH and progressive sperm motility. Interestingly, using immunofluorescence, we documented for the first time that AMH type-II receptor (AMH-R2) is expressed in ejaculated human spermatozoa and gonadotrophic cells in postmortem pituitary gland. Conclusions A new age-specific reference range for serum AMH and AMH/tT was established. Moreover, AMH-R2 expression in human spermatozoa and gonadotrophic cells, together with the relationship between serum AMH levels and sperm motility or mean FSH levels, highlight new potential functions of AMH in regulating sperm motility or FSH secretion in adult men.

With the expand of the population’s average age, the incidence of neurodegenerative disorders has dramatically increased over the last decades. Alzheimer disease (AD) which is the most prevalent neurodegenerative disease is mostly sporadic and primarily characterized by cognitive deficits and neuropathological lesions such as amyloid -β (Aβ) plaques and neurofibrillary tangles composed of hyper- and/or abnormally phosphorylated Tau protein. AD is considered a complex disease that arises from the interaction between environmental and genetic factors, modulated by epigenetic mechanisms. Besides the well-described cognitive decline, AD patients also exhibit metabolic impairments. Metabolic and cognitive perturbations are indeed frequently observed in the Developmental Origin of Health and Diseases (DOHaD) field of research which proposes that environmental perturbations during the perinatal period determine the susceptibility to pathological conditions later in life. In this review, we explored the potential influence of early environmental exposure to risk factors (maternal stress, malnutrition, xenobiotics, chemical factors … ) and the involvement of epigenetic mechanisms on the programming of late-onset AD. Animal models indicate that offspring exposed to early-life stress during gestation and/or lactation increase both AD lesions, lead to defects in synaptic plasticity and finally to cognitive impairments. This long-lasting epigenetic programming could be modulated by factors such as nutriceuticals, epigenetic modifiers or psychosocial behaviour, offering thus future therapeutic opportunity to protect from AD development.

Alzheimer’s disease (AD) is the leading cause of dementia. While impaired glucose homeostasis has been shown to increase AD risk and pathological loss of tau function, the latter has been suggested to contribute to the emergence of the glucose homeostasis alterations observed in AD patients. However, the links between tau impairments and glucose homeostasis, remain unclear. In this context, the present study aimed at investigating the metabolic phenotype of a new tau knock-in (KI) mouse model, expressing, at a physiological level, a human tau protein bearing the P301L mutation under the control of the endogenous mouse Mapt promoter. Metabolic investigations revealed that, while under chow diet tau KI mice do not exhibit significant metabolic impairments, male but not female tau KI animals under High-Fat Diet (HFD) exhibited higher insulinemia as well as glucose intolerance as compared to control littermates. Using immunofluorescence, tau protein was found colocalized with insulin in the β cells of pancreatic islets in both mouse (WT, KI) and human pancreas. Isolated islets from tau KI and tau knock-out mice exhibited impaired glucose-stimulated insulin secretion (GSIS), an effect recapitulated in the mouse pancreatic β-cell line (MIN6) following tau knock-down. Altogether, our data indicate that loss of tau function in tau KI mice and, particularly, dysfunction of pancreatic β cells might promote glucose homeostasis impairments and contribute to metabolic changes observed in AD.