scholarly journals A novel approach to nonsurgical sterilization; application of menadione‐modified gonocyte‐targeting M13 bacteriophage for germ cell ablation in utero

2020 ◽  
Vol 8 (5) ◽  
Author(s):  
Barbara A. Fraser ◽  
Kasey Miller ◽  
Natalie A. Trigg ◽  
Nathan D. Smith ◽  
Patrick S. Western ◽  
...  
Keyword(s):  
Germ Cell ◽  
In Utero ◽  
M13 Bacteriophage ◽  
Cell Ablation ◽  
Novel Approach ◽  
Nonsurgical Sterilization

scholarly journals A Novel Pharmacogenetic Model for Highly Efficient Ablation of Oligodendrocyte Progenitor Cells in the Adult Mouse CNS

2021 ◽  
Author(s):  
Yao Lulu Xing ◽  
Bernard H.A. Chuang ◽  
Jasmine Poh ◽  
Kaveh Moradi ◽  
Stanislaw Mitew ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Adult Mouse ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Cell Ablation ◽  
Novel Approach ◽  
Anterior Forebrain ◽  
Health And Disease ◽  
The Brain ◽  
Advance Knowledge

Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent central nervous system have been limited by methodological challenges resulting in only partial and transient OPC depletion. We have developed a novel pharmacogenetic model of conditional OPC ablation, resulting in the elimination of 99.7% of all OPCs throughout the brain. By combining recombinase-based transgenic and viral strategies for targeting of OPCs and ventricular-subventricular zone (V-SVZ)-derived neural precursor cells (NPCs), we found that new PDGFRα-expressing cells born in the V-SVZ repopulated the OPC-deficient brain starting 12 days after OPC ablation. Our data reveal that OPC depletion induces V-SVZ-derived NPCs to generate vast numbers of PDGFRα+/NG2+ cells with the capacity to migrate and proliferate extensively throughout the dorsal anterior forebrain. Further application of this novel approach to ablate OPCs will advance knowledge of the function of both OPCs and oligodendrogenic NPCs in health and disease.

scholarly journals Vinclozolin Exposure in Utero Induces Postpubertal Prostatitis and Reduces Sperm Production via a Reversible Hormone-Regulated Mechanism

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 783-792 ◽  
Author(s):  
Prue A. Cowin ◽  
Elspeth Gold ◽  
Jasna Aleksova ◽  
Moira K. O'Bryan ◽  
Paul M. D. Foster ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Apoptosis ◽  
Reproductive Tract ◽  
Nuclear Factor Κb ◽  
In Utero ◽  
High Dose ◽  
Nuclear Factor ◽  
Testicular Germ Cell ◽  
Male Reproductive Tract ◽  
Germ Cell Apoptosis

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-κB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, −3A, −3B, and −3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-κB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

Experimental cryptorchidism enhances testicular susceptibility to dibutyl phthalate or acrylamide in Sprague-Dawley rats

2019 ◽  
Vol 38 (8) ◽  
pp. 899-913 ◽  
Author(s):  
NP de Souza ◽  
AP Ferragut Cardoso ◽  
LMM Gomide ◽  
TRR Lima ◽  
HA Miot ◽  
...  
Keyword(s):  
Germ Cell ◽  
Dibutyl Phthalate ◽  
Reproductive Tract ◽  
In Utero ◽  
Seminiferous Tubules ◽  
Postnatal Exposure ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Extended Exposure

Cryptorchidism (CPT), the most common male congenital abnormality, is variably associated with other male reproductive tract problems. We evaluated if cryptorchid rats develop enhanced testicular susceptibility to dibutyl phthalate (DBP) or acrylamide (AA) after extended exposure. Three studies with rats were performed: (1) in utero and postnatal exposure to DBP or AA; (2) establishment of CPT and orchiopexy; and (3) in utero and postnatal exposures to DBP or AA associated with CPT/orchiopexy. Seminiferous tubules were histologically scored according to the severity of lesions: (1) Rats exposed to DBP (score 1.5) or AA (score 1.1) presented mostly preserved spermatogenesis. Some seminiferous tubules showed vacuolated germinative epithelium, germ cell apoptosis, and a Sertoli cell-only (SCO) pattern. (2) CPT (score 3.3) resulted in decreased absolute testes weights, degenerated and SCO tubules, and spermatogenesis arrest that were reversed by orchiopexy (score 1.1). (3) Exposure to DBP or AA with CPT/orchiopexy led to atrophic testes, spermatogenesis arrest, germ cell exfoliation/multinucleation, and SCO tubules (both chemicals score 2.5). Exposure to chemicals such as DBP or AA prevented the recovery of cryptorchid testes by orchiopexy. The possible role of environmental contaminants should be considered when looking for factors that modulate human testicular disorders associated with CPT.

Evaluation of degenerating germ cells in normal juvenile mice

Genome ◽  
2009 ◽  
Vol 52 (10) ◽  
pp. 891-896 ◽  
Author(s):  
Anastassia Trifonova ◽  
Peter B. Moens
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Germ Cells ◽  
Normal Component ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Electron Microscopic ◽  
Cell Degeneration ◽  
Novel Approach ◽  
Two Generations ◽  
Germ Cell Degeneration

Absence of spermiogenesis in mice with meiotic defects complicates the staging of meiotic arrest using light microscopy. Consequently, new methodologies are required to establish accurate relationships among germ cells. In this study, we utilized a novel approach to analyze germ cell degeneration in juvenile mice. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in combination with meiosis-specific antibodies. Germ cell degeneration is a normal component of early spermatogenesis in juvenile mice. The incidence of germ cell death was monitored at various postnatal ages of mice using the TUNEL assay to quantify the incidence of apoptosis. Cell death occurred predominantly at 15.5 days after birth. It was found that groups of apoptotic cells were apparent in tubules containing two generations of spermatocytes that form in two progressive cohorts. Electron microscopic observations further illustrated that the majority of cells in the first cohort are in late pachytene, while groups of cells in the second cohort can degenerate in early pachytene. The methodology utilized in this study is significant because it allows one to accurately determine the point at which germ cells arrest. Consequently, we believe that these methods can be applied to study animals with meiotic defects that prevent spermiogenesis.

scholarly journals Alteration of Transforming Growth Factor-β Signaling System Expression in Adult Rat Germ Cells with a Chronic Apoptotic Cell Death Process after Fetal Androgen Disruption

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5135-5143 ◽  
Author(s):  
Magali Maire ◽  
Anne Florin ◽  
Krisztian Kaszas ◽  
Daniel Regnier ◽  
Pierre Contard ◽  
...  
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Germ Cells ◽  
Apoptotic Cell ◽  
In Utero ◽  
Apoptotic Cell Death ◽  
Death Process ◽  
Rat Testis ◽  
Adult Rat ◽  
Cell Death Process

In utero exposure to chemicals with antiandrogen activity induces undescended testis, hypospadias, and sub- or infertility. The hypospermatogenesis observed in the adult rat testis exposed in utero to the antiandrogen flutamide has been reported to be a result of a long-term apoptotic cell death process in mature germ cells. However, little if anything is known about the upstream signaling mechanisms controlling this apoptosis. In the present study, we have investigated the possibility that the TGF-β signaling pathway may be at play in this control of the apoptotic germ cell death process. By using a model of adult rat exposed in utero to 0, 0.4, 2, or 10 mg/kg·d flutamide, we observed that pro-TGF-β signaling members, such as the three isoforms of TGF-β ligands (TGF-β1–3), the two TGF-β receptors (TGF-βRI and -RII) and the R-Smads Smad 1, Smad 2, Smad 3, and Smad 5 were inhibited at the mRNA and protein levels, whereas the anti-TGF-β signaling member Smad 7 was overexpressed. Furthermore, we report that the overexpression of Smad 7 mRNA could induce an activation of c-Jun N-terminal kinase, because of the observed c-Jun overexpression, activation, and nuclear translocation leading to an increase in the transcription of the proapoptotic factor Fas-L. Together, the alterations of TGF-β signaling may represent upstream mechanisms underlying the adult germ cell apoptotic process evidenced in adult rat testis exposed in utero to antiandrogenic compounds such as flutamide.

Christian Humility and the Goods of Perinatal Hospice

2021 ◽  
Author(s):  
Aaron D Cobb
Keyword(s):  
Hospice Care ◽  
In Utero ◽  
Novel Approach ◽  
Wide Range ◽  
Perinatal Hospice

Abstract Perinatal palliative and hospice care (hereafter, perinatal hospice) is a novel approach to addressing a family’s varied needs following an adverse in utero diagnosis. Christian defenses of perinatal hospice tend to focus on its role as an ethical alternative to abortion. Although these analyses are important, they do not provide adequate grounds to characterize the wide range of goods realized through this compassionate form of care. This essay draws on an analysis of the Christian virtue of humility to highlight the ways a Christian virtue-based defense of perinatal hospice can account for these goods. I argue that humility can play an important facilitating role in helping Christian physicians to meet the needs of families in profoundly difficult circumstances.

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