A single locus on the X chromosome codes for androgen receptor (AR) although this gene is subject to alternative splicing. AR is expressed in multiple tissues in males and females and is essential for reproductive success in the male. Since male and female mice are viable following naturally occurring and engineered loss of function with male mice infertile as anticipated, functional deletion of AR in pigs was hypothesized to provide a genetic containment strategy for males with edited genomes. In addition, deletion of AR might be a method to manage boar taint, hence contributing to a perceived improvement in animal welfare. The CRISPR/Cas9 technology was used to edit either exon 2 or exon 5 of the pig AR gene. Although pregnancies were established following embryo transfer of edited embryos, they were not maintained beyond day 25. Furthermore, normal M:F sex ratios were present in edited blastocysts and 19-day fetuses, but all fetuses recovered on day 21 or later were female. The pig AR gene differs from the mouse in having a U2 spliceosome component encoded in the intronic region. Hence, the absence of fetal survival beyond day 25 may be due to interference with the U2 component rather than AR.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497509PMC
http://dx.doi.org/10.1038/s41598-023-41665-6DOI Listing

Publication Analysis

Top Keywords

androgen receptor
8
spliceosome component
8
pig gene
8
gender disparity
4
disparity survival
4
survival early
4
early porcine
4
porcine fetuses
4
fetuses altered
4
altered androgen
4

Similar Publications

Supraphysiological androgen (SPA) treatment can paradoxically restrict growth of castration-resistant prostate cancer with high androgen receptor (AR) activity, which is the basis for use of Bipolar Androgen Therapy (BAT) for patients with this disease. While androgens are widely appreciated to enhance anabolic metabolism, how SPA-mediated metabolic changes alter prostate cancer progression and therapy response is unknown. Here, we report that SPA markedly increased intracellular and secreted polyamines in prostate cancer models.

View Article and Find Full Text PDF

Metastatic prostate cancer remains incurable. Though significant progress has been made in the field, the search for agents that improve outcomes for patients is ongoing. Several clinical trials have explored the benefit of combining PARP inhibitors (PARPi) with androgen receptor pathway inhibitors (ARPIs) for metastatic castrate resistant prostate cancer (mCRPC), especially those cancers with alterations in homologous recombination repair (HRR) genes.

View Article and Find Full Text PDF

Lepidium meyenii (Maca) is a plant that has nutritional benefits and increases the effectiveness of male reproduction. In this study, oxidative stress-exposed New Zealand rabbits were used to assess the ameliorative effects of daily Maca ingestion on testicular and epididymal tissues as well as the quality of fresh and frozen/thawed sperm. Twenty-four 40-week-old, healthy New Zealand white male rabbits were divided into four groups.

View Article and Find Full Text PDF

Increased nuclear factor I-mediated chromatin access drives transition to androgen receptor splice variant dependence in prostate cancer.

Cell Rep

December 2024

Department of Medicine and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Androgen receptor (AR) splice variants, of which ARv7 is the most common, are increased in castration-resistant prostate cancer, but the extent to which they drive AR activity is unclear. We generated a subline of VCaP cells (VCaP16) that is resistant to the AR inhibitor enzalutamide (ENZ). AR activity in VCaP16 is driven by ARv7, independently of full-length AR (ARfl), and its cistrome and transcriptome mirror those of ARfl in VCaP cells.

View Article and Find Full Text PDF

The damaged organ may experience severe pathological alterations as a result of tissue ischemia-reperfusion (I/R). The study of stem cell-based repair therapies is actively being conducted, and the outcomes and therapeutic potential of these cells are both promising. Autophagy checks protein homeostasis by breaking down huge damaged proteins or organelles.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!