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Crowder, C. M.

Publications and source records attributed to Crowder, C. M..

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G protein-coupled estrogen receptor is not required for sex determination or ovary function in zebrafish

Estrogens regulate vertebrate development and function through binding to nuclear estrogen receptors alpha and beta (ER, ER{beta}) and the G protein-coupled estrogen receptor (GPER). Studies in mutant animal models demonstrated that ER and ER{beta} are required for normal ovary development and function. However, the degree to which GPER signaling contributes to ovary development and function is less well understood. Previous studies using cultured fish oocytes found that estradiol inhibits oocyte maturation in a GPER-dependent manner, but whether GPER regulates oocyte maturation in vivo is not known. To test the hypothesis that GPER regulates oocyte maturation in vivo, we assayed ovary development and function in gper mutant zebrafish. We found that homozygous mutant gper embryos developed into male and female adults with normal sex ratios and fertility. Adult mutant fish exhibited normal secondary sex characteristics and fertility. Additionally, mutant ovaries were histologically normal. We observed no differences in the number of immature versus mature oocytes in mutant versus wild-type ovaries from both young and aged adults. Furthermore, expression of genes associated with sex determination and ovary function were normal in gper mutant ovaries compared to wild type. Our findings suggest that GPER is not required for sex determination, ovary development or fertility in zebrafish.

developmental biology

Nuclear androgen receptor regulates testes organization and oocyte maturation in zebrafish

Androgens act through the nuclear androgen receptor (AR) to regulate gonad differentiation and development. In mice, AR is required for spermatogenesis, testis development and formation of external genitalia in males and oocyte maturation in females. However, the extent to which these phenotypes are conserved in nonmammalian vertebrates is not well understood, because mutations in AR have not been generated in any other species. Here, we generate zebrafish with a mutation in the ar gene and examine the role of AR on sexual differentiation and gonad development. We find that zebrafish AR is not required for male sexual differentiation, since a portion of ar mutants develop a testis. However, we show that in zebrafish, as in mice, AR is required for the development of secondary sexual characteristics and for proper organization of the testis in males and for oocyte maturation in females. Additionally, we find that zebrafish ar mutant males have functional, mature sperm present in their testis, but are infertile due to an inability to release sperm. These findings suggest that AR is required for male sexual development and fertility, but not essential for sexual differentiation in zebrafish. The ar mutant we developed will be useful for modeling human endocrine function in zebrafish.

developmental biology