Gamete abnormalities and reproductive system tumors have become a dominant cause of infertility, troubling people globally. In recent years, increasing evidence emerged and found that N6-methyladenosine (m6A) played a leading role in reproduction. The biological effects of m6A modification are dynamically and reversibly regulated by methyltransferases (writers), WTAP, METTL3, METTL14 and KIAA1429, demethylases (erasers), FTO and ALKBH5, and m6A binding proteins (readers), including YTH domain. In this review, we highlight the change of m6A modification in abnormal oogenesis, female reproductive system diseases including reproductive system tumors, adenomyosis, endometriosis, premature ovarian failure and polycystic ovary syndrome. Moreover, we review some of the mechanisms and the specific modified genes that have been identified. Especially, with the underlying mechanisms being uncovered, m6A and its protein machineries are expected to be the markers and targets for the diagnosis and treatment of female reproductive dysfunction.

This systematic review and meta-analysis was aimed at determining whether paternal age is a risk factor for offspring birth defects. A total of 38 and 11 studies were included in the systematic review and meta-analysis, respectively. Compared with reference, fathers aged 25 to 29, young fathers (< 20 years) could increase the risk of urogenital abnormalities (OR: 1.50, 95 % CI: 1.03-2.19) and chromosome disorders (OR: 1.38, 95 % CI: 1.12-1.52) in their offsprings; old fathers (≥ 40 years) could increase the risk of cardiovascular abnormalities (OR: 1.10, 95 % CI: 1.01-1.20), facial deformities (OR: 1.08, 95 % CI: 1.00-1.17), urogenital abnormalities (OR: 1.28, 95 % CI: 1.07-1.52), and chromosome disorders (OR: 1.30, 95 % CI: 1.12-1.52). Our study indicated that paternal age is associated with a moderate increase in the incidence of urogenital and cardiovascular abnormalities, facial deformities, and chromosome disorders. PubMed, Web of Science, the Cochrane Library, and Embase were searched for relevant literatures from 1960 to February 2020. The systematic review follows PRISMA guidelines. Relevant meta-analyses were performed.

Mancozeb (MZ), an antibacterial pesticide, has been linked to reproductive toxicity, neurotoxicity, and endocrine disruption. However, whether MZ has cardiactoxicity is unclear. In this study, the cardiotoxic effects of exposure to environment-related MZ concentrations ranging from 1.88 μM to 7.52 μM were evaluated at the larval stage of zebrafish. Transcriptome sequencing predicted the mechanism of MZ-induced cardiac developmental toxicity in zebrafish by enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Consistent with morphological changes, the osm, pfkfb3, foxh1, stc1, and nrarpb genes may effect normal development of zebrafish heart by activating NOTCH signaling pathways, resulting in pericardial edema, myocardial fibrosis, and congestion in the heart area. Moreover, differential gene expression analysis indicated that cyp-related genes (cyp1c2 and cyp3c3) were significantly upregulated after MZ treatment, which may be related to apoptosis of myocardial cells. These results were verified by real-time quantitative RT-qPCR and acridine orange staining. Our findings suggest that MZ-mediated cardiotoxic development of zebrafish larvae may be related to the activation of Notch and apoptosis-related signaling pathways.