Wt1 gene encodes a nuclear transcription factor which is specifically expressed in ovarian granulosa cells and testicular Sertoli cells. Our previous studies demonstrated that Wt1 is required for the lineage specification of supporting cells and inactivation of Wt1 results in Sertoli cells to Leydig-like cells transformation. To test whether Wt1 is also involved in lineage maintenance of granulosa cells during ovary development, Wt1 was specifically deleted in pre-granulosa cells using Foxl2-cre. We found that the female Wt1−/flox; Foxl2-cre mice were infertile with atrophic ovaries and no growing follicles with multiple layers of granulosa cells were observed. A large number of 3β-HSD-positive steroidogenic cells were detected in ovaries of Wt1−/flox; Foxl2-cre mice during embryonic stage and these cells were derived from Foxl2-expressing pre-granulosa cells. The quantitative results showed the expression of granulosa cell marker genes (Foxl2, Follistatin) was downregulated and steroidogenic cell marker genes (3β-HSD, Cyp11a1, Star and Sf1) was dramatically increased in Wt1−/flox; Foxl2-cre ovaries. We also found that the meiosis of germ cells in Wt1−/flox; Foxl2-cre ovaries was delayed but not arrested. This study demonstrates that Wt1 is required for lineage maintenance of granulosa cells and inactivation of Wt1 results in pre-granulosa cells to steroidogenic cells transformation which in turn causes the defect of ovary development.
Coridius chinensis (C. chinensis) is a traditional Chinese medicine that has been used to treat pain, erectile dysfunction, and other diseases. Our previous study demonstrated that manganese‐induced reproductive damage was partially rescued by a medium dose of C. chinensis treatment in rat. However, the underlying mechanism is unknown. In this study, we found that the weight of reproductive organs and the sperm count in manganese‐exposed rat were partially rescued by C. chinensis extracts (CcE) treatment. The number of apoptotic cells was significantly decreased and the expression of malondialdehyde, cytochrome c, and caspase‐3 in manganese‐exposed rats was significantly decreased after high dose of CcE treatment. Further studies revealed that the activity of superoxide dismutase, total antioxidant capacity, and glutathione peroxidase enzymes was significantly increased in testis tissues and serum of manganese‐exposed rats with high dose of CcE treatment. Taken together, the results of this study suggest that CcE inhibits the Mn2+‐induced apoptosis in testes by inducing the activity of antioxidants.
Wilms’ tumour 1 (Wt1) encodes a zinc finger nuclear transcription factor which is mutated in 15–20% of Wilms’ tumor, a pediatric kidney tumor. Wt1 has been found to be involved in the development of many organs. In gonads, Wt1 is expressed in genital ridge somatic cells before sex determination, and its expression is maintained in Sertoli cells and granulosa cells after sex determination. It has been demonstrated that Wt1 is required for the survival of the genital ridge cells. Homozygous mutation of Wt1 causes gonad agenesis. Recent studies find that Wt1 plays important roles in lineage specification and maintenance of gonad somatic cells. In this review, we will summarize the recent research works about Wt1 in gonadal somatic cell differentiation.
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