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. 2020 Jan 16;11:330. doi: 10.1038/s41467-019-14055-8

Fig. 2. Mechanisms of AZT-sensitive FOA.

Fig. 2

a GO enrichment in untreated (UT) and AZT-treated E18.5 ovaries and oocytes. b mRNA abundance (FPKM) in UT and AZT-treated E18.5 ovaries and oocytes for immunity and apoptosis genes. a, b Analysis from mRNA-sequencing data containing n > 2 biological replicates sequenced per condition, each containing sorted oocytes or ovaries from > 6 WT CD1 embryos. c Immunofluorescence labeling of macrophage marker F4/80 and L1 ORF1p-labeling oocytes in E18.5 Chk2+/− and Chk2−/− + AZT ovaries. Ovaries are separated from surrounding tissue for quantification of macrophages in ovary with dotted line, boundary determined using L1 ORF1p as a marker of oocytes. Scale bar:50 μm. d Quantification of macrophage number per ovary section area in Chk2+/− (n = 6) and Chk2−/− + AZT (n = 5) conditions. Dots indicate independent ovary sections from three ovary samples per condition; data are mean + SD. Stats by Mann–Whitney test, **p < 0.01. e Model of L1 ORF2p activities and their relationship to molecular triggers and mechanisms of FOA. Reverse transcriptase (RT) activity of ORF2p is inhibited by AZT and associated with L1 reverse transcription intermediates, activation of the complement system and recruitment of immune cells. Endonuclease (EN) activity of ORF2p creates DNA breaks that in addition to other common meiotic defects, activates the DNA damage checkpoint through CHK2.