Studies in teleosts suggest that progestins have crucial functions during early spermatogenesis. However, the role of the different progestin receptors in these mechanisms is poorly understood. In this work, we investigated the expression pattern and hormonal regulation of the classical nuclear progestin receptor (Pgr) in the gilthead seabream at three different stages of spermatogenesis: the resting (postspawning) phase, onset of spermatogenesis, and spermiation. Immunolocalization experiments using a seabream specific Pgr antibody revealed that the receptor was expressed in Sertoli and Leydig cells, and also in a subset of spermatogonia type A, throughout spermatogenesis. Short-term treatment of testis explants with 17β-estradiol (E2) increased pgr mRNA expression at all stages, while the progestin 17α,20β-dihydroxy-4-pregnen-3-one (17,20βP) had the opposite effect. At the resting stage, Sertoli cell Pgr expression was positively correlated with the occurrence of proliferating spermatogonia type A in the tubules, and both processes were incremented in vitro by E2 likely through the estrogen receptor alpha (Era) expressed in Sertoli and Leydig cells. In contrast, treatment with 17,20βP downregulated Pgr expression in somatic cells. The androgen 11-ketotestosterone (11-KT) upregulated pgr expression in Leydig cells and promoted the proliferation of mostly spermatogonia type B, but only during spermiation. No relationship between the changes in the cell type-specific expression of the Pgr with the entry into meiosis of germ cells was found. These data suggest a differential steroid regulation of Pgr expression during seabream spermatogenesis and the potential interplay of the E2/Era and 17,20βP/Pgr pathways for the maintenance of spermatogonial renewal rather than entry into meiosis.
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Sci Rep
January 2025
Department of Medical and Surgical Sciences (DIMEC), General Pathology Building, University of Bologna, Bologna, Italy.
The β1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) which synthesizes the histo-blood group antigen Sd is highly expressed by normal colon, but it is dramatically down-regulated in colorectal cancer (CRC). High B4GALNT2 expression in CRC tissues is a marker of longer survival. The molecular bases of B4GALNT2 inhibition in CRC are largely obscure.
View Article and Find Full Text PDFExp Neurol
January 2025
Department of Neurology, University of Virginia, Charlottesville, VA 22908, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; UVA Brain Institute, University of Virginia, Charlottesville, VA 22908, USA.
Migraine patients often experience sensory symptoms called auras accompanying the headaches. Cortical spreading depression (CSD), a slow-propagating wave of neuroglial depolarization followed by hyperpolarization is proposed to be the neurological mechanism underlying these auras. We have previously found that progesterone regulates susceptibility to migraine through progesterone receptor (PR) activation.
View Article and Find Full Text PDFWhile most pregnancies are affected by nausea and vomiting, hyperemesis gravidarum (HG) is at the severe end of the clinical spectrum and is associated with dehydration, undernutrition, and adverse maternal, fetal, and child outcomes. Herein we performed a multi-ancestry genome-wide association study (GWAS) of severe nausea and vomiting of pregnancy of 10,974 cases and 461,461 controls across European, Asian, African, and Latino ancestries. We identified ten significantly associated loci, of which six were novel ( , , , , , and and confirmed previous genome-wide significant associations with risk genes , , , and .
View Article and Find Full Text PDFNat Commun
January 2025
Center for Early Detection and Interception of Blood Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.
View Article and Find Full Text PDFCell Discov
January 2025
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
We investigated a novel cancer immunotherapy strategy that effectively suppresses tumor growth in multiple solid tumor models and significantly extends the lifespan of tumor-bearing mice by introducing pathogen antigens into tumors via mRNA-lipid nanoparticles. The pre-existing immunity against the pathogen antigen can significantly enhance the efficacy of this approach. In mice previously immunized with BNT162b2, an mRNA-based COVID-19 vaccine encoding the spike protein of the SARS-CoV-2 virus, intratumoral injections of the same vaccine efficiently tagged the tumor cells with mRNA-expressed spike protein.
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