Early Castration in Horses Does Not Impact Osteoarticular Metabolism.

The castration of stallions is traditionally performed after puberty, at around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we aimed to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses.

Ex vivo effects of 17β-estradiol on the prepubertal rat testis.

Although it is well established that testis produces estrogens, their precise effect is not fully documented, particularly during the prepubertal period. In a previous in vivo study, we demonstrated that an exposure of prepubertal rats (15-30 days post-partum (dpp)) to 17β-estradiol (E2) delays the establishment of spermatogenesis. In order to characterize the mechanisms of action and the direct targets of E2 on the immature testis, we developed an organotypic culture model of testicular explants obtained from prepubertal rats (15, 20 and 25 dpp).

Effects of bisphenol A and estradiol in adult rat testis after prepubertal and pubertal exposure.

Over the past few decades, male fertility has been decreasing worldwide. Many studies attribute this outcome to endocrine disruptors exposure such as bisphenol A (BPA), which is a chemical compound used in plastics synthesis and exhibiting estrogenic activity. In order to assess how the window of exposure modulates the effects of BPA on the testis, prepubertal (15 dpp to 30 dpp) and pubertal (60 dpp to 75 dpp) male Sprague-Dawley rats were exposed to BPA (50 µg/kg bw/day), 17-β-estradiol (E2) (20 µg/kg bw/day) as a positive control, or to a combination of these compounds.

Investigation of equine testis contribution to vitamin D bioactivation.

Although vitamin D acts in various biological processes, it plays a critical role in the maintenance of bone health, and regulates calcium homeostasis. In humans and rodents, the main tissues involved in vitamin D metabolism are the liver and the kidneys, however it has been shown that the testis has strongly participated in its bioactivation. Indeed, in these different species, enzymes metabolizing vitamin D (CYP27A1, CYP27B1 and CYP2R1) have been demonstrated in this tissue.

Estrogen receptor α regulates the expression of syndecan-1 in human breast carcinoma cells.

Breast cancer (BC) is the primary cause of cancer-related mortality among women. Patients who express the estrogen receptor (ER), which mediates the tumorigenic effects of estrogens, respond to antihormonal therapy. Loss of ER expression or acquired resistance to E2 is associated with aggressive malignant phenotypes, which lead to relapse.

MST1/Hippo promoter gene methylation predicts poor survival in patients with malignant pleural mesothelioma in the IFCT-GFPC-0701 MAPS Phase 3 trial.

Background: The Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS/NCT00651456) phase 3 trial demonstrated the superiority of bevacizumab plus pemetrexed-cisplatin triplet over chemotherapy alone in 448 malignant pleural mesothelioma (MPM) patients. Here, we evaluated the prognostic role of Hippo pathway gene promoter methylation.

Methods: Promoter methylations were assayed using methylation-specific polymerase chain reaction in samples from 223 MAPS patients, evaluating their prognostic value for overall survival (OS) and disease-free survival in univariate and multivariate analyses.

Increase in hyaluronic acid degradation decreases the expression of estrogen receptor alpha in MCF7 breast cancer cell line.

The loss of estrogen receptor α (ERα) expression in breast cancer constitutes a major hallmark of tumor progression to metastasis and is generally correlated to a strong increase in Hyaluronic Acid (HA) turnover. The aim of our study was to search for a putative link between these two major events of breast cancer progression in the estrogen receptor-positive (ER+) MCF7 breast cancer cell line. The increase in HA turnover was performed by stable overexpression of the standard CD44 (CD44S) isoform and also by treatment with exogenous Hyaluronidase (Hyal) to allow an increase in HA catabolism.

Hyaluronate synthase-2 overexpression alters estrogen dependence and induces histone deacetylase inhibitor-like effects on ER-driven genes in MCF7 breast tumor cells.

In breast carcinoma cells, high levels of hyaluronan (HA) and its CD44 receptor are frequently associated with alteration in estrogen signaling. We demonstrate that stable hyaluronate synthase 2 (HAS2) overexpression in estrogen receptor α (ERα) -positive MCF7 cells oppositely altered estrogen dependence of cell growth and its sensitivity towards antiestrogens. Albeit without effect on ERα expression and estradiol binding properties, HAS2 overexpression increased ERα Ser118 phosphorylation as well as transcriptional activity of estrogen in an ERE-luciferase reporter gene assay.

No evidence for genetic association between glutamate transporter EAAT2 and Devic's neuromyelitis optica in caucasians and afro-caribbeans.

Devic's neuromyelitis optica (NMO) is a severe inflammatory and autoimmune disease producing demyelinating lesions. Recent data suggest that a complex genetic component could be involved. While impairment of glutamate homeostasis has emerged as a contributing etiological factor in NMO, a genetic alteration of Excitatory Amino Acid Transporter 2 (EAAT2/SLC1A2), the major glutamate transporter in the Central Nervous System (CNS), could contribute to glutamate excitotoxicity and then must be considered.

GnRH agonist and GnRH antagonist protocols in ovarian stimulation: differential regulation pathway of aromatase expression in human granulosa cells.

Gonadotrophin-releasing hormone (GnRH) agonists and antagonists have been widely used to prevent premature LH surge during ovarian stimulation. However, studies have shown a significantly lower serum oestradiol concentration on the day of human chorionic gonadotrophin administration for cycles using GnRH antagonist. This study compared aromatase gene expression in granulosa lutein cells from 50 women randomly assigned to receive either GnRH agonist (group 1, n=28) or GnRH antagonist (group 2, n=22).

Electrotransfer of cDNA coding for a heterologous prion protein generates autoantibodies against native murine prion protein in wild-type mice.

Prion diseases (e.g., Creutzfeldt-Jakob disease in humans) are always fatal neurodegenerative disorders characterized by conversion of the ubiquitous cellular prion protein (PrP(c)) into a pathological conformer.

Curative properties of antibodies against prion protein: a comparative in vitro study of monovalent fragments and divalent antibodies.

Prion diseases, which include Creutzfeldt-Jakob disease (CJD) in humans, are a group of devastating neurodegenerative disorders for which no therapy is yet available. However, passive immunotherapy appears to be a promising therapeutic approach, given that antibodies against the cellular prion protein (PrPc) have been shown in vitro to antagonize deposition of the disease-associated prion protein (PrPSc). Nevertheless, in vivo deleterious side effects of injected anti-PrP antibodies have been reported, mainly due to their Fc fragments and divalence.

Generating antibodies against the native form of the human prion protein (hPrP) in wild-type animals: a comparison between DNA and protein immunizations.

Generation of therapeutic antibodies against human proteins is hampered by the difficulty of obtaining large quantities of correctly folded immunogens when following classic immunization procedures. Here we compared several genetic immunization protocols for their potential ability to generate high levels of antibodies against proteins expressed in their native form. We chose as a model the prion protein (PrP) because it has been demonstrated that the recognition of the native conformation of PrP is an absolute prerequisite for anti-PrP antibodies to be used as therapeutic tools for prion diseases, a group of lethal neurodegenerative disorders.

Polyclonal anti-idiotypic antibodies which mimic an epitope of the human prion protein.

Immunization with anti-idiotypic (anti-Id) antibodies, used as surrogate antigens, has led to promising results, notably in active immunotherapy of cancers, essentially because it breaks immunological tolerance against self-tumor-associated antigens. The aim of the present study was to provide a proof-of-principle that this vaccination approach could be envisaged also in the field of prion diseases, caused by the accumulation of an aggregated pathological isoform of the highly tolerogenic self-prion protein (PrP), and for which no therapy is available. We investigated the possibility of raising anti-Id antibodies mimicking the human PrP (hPrP), using as immunogens either a peptide derived from the paratope of an anti-PrP mAb or the entire antibody.

The role of p63 in germ cell apoptosis in the developing testis.

The fetal and neonatal development of male germ cells (gonocytes) is a poorly understood but crucial process for establishing fertility. In rodents, gonocytes go through two phases of proliferation accompanied by apoptosis and separated by a quiescent period during the end of fetal development. P63 is a member of the P53 gene family that yields six isoforms.

Differential regulation of two 3' end variants of P450 aromatase transcripts and of a new truncated aromatase protein in rabbit preovulatory granulosa cells.

In rabbit granulosa cells, two cytochrome P450 aromatase (P450 arom) mRNAs issued from promoter II were described: a full-length and a truncated transcript. Western blot analysis showed two P450 arom proteins with apparent molecular masses of 53 and 46 kDa, which are consistent with the predicted theoretical sizes of proteins encoded by these two transcripts. To examine the involvement of the truncated transcript in the regulation of P450 arom gene expression, the level of each transcript was specifically quantified in cultured granulosa cells by competitive quantitative RT-PCR.