To better understand transcriptional regulation during human oogenesis and pre-implantation development, we defined stage-specific transcription, which revealed the cleavage stage as highly distinctive. Here, we present multiple lines of evidence that a eutherian-specific, multi-copy retrogene, DUX4, encodes a transcription factor which activates hundreds of endogenous genes (e.g. ZSCAN4, ZFP352, KDM4E) and retroviral elements (MERVL/HERVL-family) that defines the cleavage-specific transcriptional programs in mouse and human. Remarkably, mouse Dux expression is both necessary and sufficient to convert mouse embryonic stem cells into two-cell embryo-like (‘2C-like’) cells, measured here by the reactivation of ‘2C’ genes and repeat elements, the loss of POU5F1 protein and chromocenters, and by the conversion of the chromatin landscape (assessed by ATAC-seq) to a state strongly resembling mouse two-cell embryos. Taken together, we propose mouse DUX and human DUX4 as major drivers of the cleavage/‘2C’ state.

Purpose The purpose of the study is to evaluate existing literature for possible associations between female infertility, infertility-associated diagnoses, and the following areas of disease: psychiatric disorders, breast cancer, ovarian cancer, endometrial cancer, cardiovascular disease, and metabolic dysfunction. Methods The design of the study is a literature review. The patients were women included in 26 selected studies due to a diagnosis of infertility or a reproductive disorder associated with infertility. This study has no interventions, and the main outcome measure is the association between female infertility or a related diagnosis and psychiatric disorders, breast cancer, ovarian cancer, endometrial cancer, cardiovascular disease, and metabolic dysfunction. Results Female infertility and related reproductive disorders may have ramifications for women beyond reproductive health. An analysis of publications shows that women with infertility had higher rates of psychiatric disorders and endometrial cancer than the general population [1][2][3][4][5][6][7][8][9][10]. Data is conflicting about whether infertile women are at increased risk for breast cancer and ovarian cancer [7,8,[10][11][12][13][14][15][16][17][18][19][20]. A generalized diagnosis of infertility was not clearly associated with an increased risk of cardiovascular disease or metabolic dysfunction, but women with infertility related to polycystic ovarian syndrome (PCOS) do appear more likely to develop cardioCapsule There is a growing body of literature addressing the impact of female infertility on long-term health. This review evaluates 26 studies, investigating possible correlations between infertility and psychiatric illness, breast cancer, ovarian cancer, endometrial cancer, cardiovascular disease, and metabolic dysfunction. Overall, higher rates of psychiatric illness and endometrial cancer were seen in infertile women. It is unclear whether infertility results in increased rates of breast cancer and ovarian cancer, and data are conflicting regarding correlations between generalized infertility and cardiovascular disease and metabolic dysfunction. This study summarizes current literature and can guide practitioners in counseling infertile patients.