The cerebellum modulates thirst.

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking.

Loss of WNT4 in the gubernaculum causes unilateral cryptorchidism and fertility defects.

Undescended testis (UDT) affects 6% of male births. Despite surgical correction, some men with unilateral UDT may experience infertility with the contralateral descended testis (CDT) showing no A-dark spermatogonia. To improve our understanding of the etiology of infertility in UDT, we generated a novel murine model of left unilateral UDT.

Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor.

Asprosin is a fasting-induced glucogenic and centrally acting orexigenic hormone. The olfactory receptor Olfr734 is known to be the hepatic receptor for asprosin that mediates its effects on glucose production, but the receptor for asprosin's orexigenic function has been unclear. Here, we have identified protein tyrosine phosphatase receptor δ (Ptprd) as the orexigenic receptor for asprosin.

PRSS50 is a testis protease responsible for proper sperm tail formation and function.

Multiple morphological abnormalities of the sperm flagella (MMAF) are a major cause of asthenoteratozoospermia. We have identified protease serine 50 (PRSS50) as having a crucial role in sperm development, because Prss50-null mice presented with impaired fertility and sperm tail abnormalities. PRSS50 could also be involved in centrosome function because these mice showed a threefold increase in acephalic sperm (head-tail junction defect), sperm with multiple heads (spermatid division defect) and sperm with multiple tails, including novel two conjoined sperm (complete or partial parts of several flagellum on the same plasma membrane).

E2F1 regulates testicular descent and controls spermatogenesis by influencing WNT4 signaling.

Cryptorchidism is the most common urologic birth defect in men and is a predisposing factor of male infertility and testicular cancer, yet the etiology remains largely unknown. microdeletions and microduplications contribute to cryptorchidism, infertility and testicular tumors. Although deletion or overexpression in mice causes spermatogenic failure, the mechanism by which influences testicular function is unknown.

Variants in ALX4 and their association with genitourinary defects.

Background: Genitourinary anomalies occur in approximately 1% of humans, but in most cases, the cause is unknown. Aristaless-like homeobox 4 (ALX4) is an important homeodomain transcription factor. ALX4 mutations in humans and mouse have been associated with craniofacial defects and genitourinary anomalies such as cryptorchidism and epispadias.

Asprosin is a centrally acting orexigenic hormone.

Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood-brain barrier and directly activates orexigenic AgRP neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight.

Paratubal Cyst Size Correlates With Obesity and Dysregulation of the Wnt Signaling Pathway.

Study Objective: Paratubal cysts (PTCs) occur in 7%-10% of women, regardless of age. Although common, PTCs often are found incidentally because of the potential for these cysts to be asymptomatic. The specific aims of the study were to determine if PTC number and size correlated with signs of hyperandrogenism and obesity, as well as to investigate the molecular profiles of these PTCs in samples derived from female adolescents.

Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin.

Isolation and Manipulation of Adipogenic Cells to Assess TGF-β Superfamily Functions.

A variety of TGF-β superfamily members affect adipocyte differentiation and function with consequential effects on energy metabolism. There has been a growing interest in this area because of the apparent influence of the BMP subgroup on brown adipose characteristics and potential application to the treatment of human obesity. In this chapter we describe methods that are useful in allowing one to assess the roles of specific members of the superfamily on adipocyte differentiation and mature adipocyte function, including the isolation and differentiation of mouse embryo fibroblasts (MEFs) to examine cell autonomous effects and the efficient transfection of two commonly used (but difficult to transfect) adipogenic cell lines, C3H/10T1/2 and 3T3-L1.

Aberrations in pseudoautosomal regions (PARs) found in infertile men with Y-chromosome microdeletions.

Context: The pseudoautosomal regions (PARs) of the Y-chromosome undergo meiotic recombination with the X-chromosome. PAR mutations are associated with infertility and mental and stature disorders.

Objective: The aim of the study was to determine whether men with Y-chromosome microdeletions have structural defects in PARs.

Mitochondrial dysfunction in obesity.

Purpose Of Review: The review highlights recent findings regarding the functions of mitochondria in adipocytes, providing an understanding of their central roles in regulating substrate metabolism, energy expenditure, disposal of reactive oxygen species (ROS), and in the pathophysiology of obesity and insulin resistance, as well as roles in the mechanisms that affect adipogenesis and mature adipocyte function.

Recent Findings: Nutrient excess leads to mitochondrial dysfunction, which in turn leads to obesity-related pathologies, in part due to the harmful effects of ROS. The recent recognition of 'ectopic' brown adipose in humans suggests that this tissue may play an underappreciated role in the control of energy expenditure.

Activin signaling: effects on body composition and mitochondrial energy metabolism.

Activin-betaA and activin-betaB (encoded by Inhba and Inhbb genes, respectively) are closely related TGF-beta superfamily members that participate in a variety of biological processes. We previously generated mice with an insertion allele at the Inhba locus, Inhba(BK). In this allele, the sequence encoding the Inhba mature domain is replaced with that of Inhbb, rendering the gene product functionally hypomorphic.

Decorin promotes plasminogen/plasmin expression within acute spinal cord injuries and by adult microglia in vitro.

Spinal cord scar tissue presents a combined physical and molecular barrier to axon regeneration. Theoretically, spinal cord injuries (SCIs) can be rendered more permissive to axon growth by either suppressing synthesis of misaligned, fibrotic scar tissue and associated axon growth inhibitors, or enzymatically degrading them. We have previously shown that acute infusion of human recombinant decorin core protein into discreet stab injuries of the rat dorsal column pathways effected a major suppression of inflammation, astrogliosis, and multiple axon growth inhibitory chondroitin sulfate proteoglycans, which combined to promote rapid axon growth across the injury site.