Membrane Progestin Receptors α and β (Paqr7 and 8) are Necessary for Oogenesis in Zebrafish

Paqr7 and paqr8 are genes encoding membrane progestin receptor αand β (mPRα and mPRβ, respectively), which are currently classified as members of the progestin and adipoQ receptor (PAQR) family. For mPRα, the first identified mPR gene, there are two paralogs in zebrafish, paqr7a and paqr7b. In order to elucidate the physiological functions of the mPR subtypes, we created gene knockout (KO) fish by editing seven paqr genes in zebrafish and analyzing their phenotypes. The null-mutant strains of paqr7a, paqr7b, and paqr8 presented no significant abnormalities in reproductive functions. Thus, we generated a triple-gene knockout (TKO) strain of these highly related genes. The TKO strain had reduced fecundity and a high percentage of abnormal embryos. The embryos exhibited various types of abnormal morphology. In histological sections, a reduction in the number of nucleoli in germinal vesicles was observed. Additionally, the distribution of the nucleolus was abnormal. The amount of 18S and 28S ribosomal RNAs in the oocytes significantly increased. These analyses indicate that paqr7a, paqr7b, and paqr8 are responsible for the production of the nucleolus, which is necessary for supplying the proper number of ribosomal RNAs into the cytoplasm of oocytes. Abnormal embryo development resulted from low-quality eggs in TKO zebrafish, suggesting that paqr7a, paqr7b, and paqr8 mutations affect oogenesis. These results indicate that Paqr7a, Paqr7b, and Paqr8 are required for the preparation of the nucleolus during oogenesis. Insufficient formation of the nucleolus resulted in a higher quantity of ribosomal RNA in the cytoplasm, causing abnormal embryo development.