Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0079731 (
B-cell lymphoma
)
16,671
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Varicocele is one of the most important causes of male infertility, as this condition leads to a decline in sperm quality. It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels, leading to oxidative stress and sperm apoptosis; however, the specific pathogenic mechanisms affecting spermatogenesis remain elusive.
Prokineticin 2
(
PK2
), a secretory protein, is associated with multiple biological processes, including cell migration, proliferation, and apoptosis. In the testis,
PK2
is expressed in spermatocytes under normal physiological conditions. To investigate the role of
PK2
in varicocele, a rat varicocele model was established to locate and quantify the expression of
PK2
and its receptor, prokineticin receptor 1 (PKR1), by immunohistochemistry and quantitative real-time PCR assays (qPCR). Moreover, H
2
O
2
was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line (GC-2) in vitro, and the apoptosis rate was detected by flow cytometry. Here, we illustrated that the expression levels of
PK2
and PKR1 were upregulated in the spermatocytes of the rat model. Administration of H
2
O
2
stimulated the overexpression of
PK2
in GC-2. Transfection of recombinant pCMV-HA-
PK2
into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3, caspase-8, and
B cell lymphoma
2-associated X; downregulating
B cell lymphoma
2; and promoting the accumulation of intracellular calcium. Overall, we revealed that the varicocele-induced oxidative stress stimulated the overexpression of
PK2
, leading to apoptosis of spermatocytes. Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.
...
PMID:Prokineticin 2 overexpression induces spermatocyte apoptosis in varicocele in rats. 3174 94
