Many long noncoding RNA (lncRNA) species have been identified in gametes. However, the biogenesis and function of other categories of lncRNAs in gametes is poorly understood. Here, we profiled the expression of lncRNAs and mRNAs in spermatogonial stem cells (SSC), type A spermatogonia (A), pachytene spermatocytes (PS) and round spermatids (RS) by microarray analysis. We analyze the total expression of lncRNA/mRNA in these four germ cells and found that the maximum number of lncRNAs expression is in A (22127), and the minimum is in PS (14456). Also, the maximum number of mRNAs is in A (19923), and the minimum is in PS (13941). Furthermore, the trend in the number of specific lncRNAs was similar to the number of specific mRNAs in each type of germ cells (e.g., maximum in A and minimum in PS). The trend in the number of lncRNAs was similar to the number of mRNAs in two continued types of germ cells (e.g., maximum in SSC to A and minimum in PS to RS). The correlation analysis showed a high correlation coefficient of lncRNAs/mRNAs expression (R = 0.992). The results suggested that the sequential expression of long noncoding RNA as mRNA gene expression exhibits coordinated changes in male spermatogenesis.

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Endometriosis, a chronic disorder characterised by the presence of endometrial-like tissue outside the uterus, is associated with iron overload and oxidative stress in the lesion. Although it is well established that iron overload can trigger ferroptosis, the results of previous studies on ferroptosis resistance and ferroptosis in endometriotic lesions are paradoxical. Here, we found that some stromal cells of the cyst walls that were in contact with the cyst fluid underwent ferroptosis. Surprisingly, endometrial stromal cell ferroptosis triggered the production of angiogenic, inflammatory and growth cytokines. In particular, angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8), promoted human umbilical vein endothelial cell (HUVEC) vascular formation in vitro. Moreover, we found that inhibition of p38 mitogen-activated protein kinase/signal transducer and activator of transcription 6 (p38 MAPK/STAT6) signalling represses VEGFA and IL8 expression when endometrial stromal cells undergo ferroptosis. Notably, VEGFA and IL8 showed localised expression and were significantly upregulated in ectopic lesions compared to control and eutopic endometrium samples from patients with endometriosis. Thus, our study reveals that endometrial stromal cell ferroptosis in the ovarian endometrioma may trigger cytokine secretion and promote angiogenesis of adjacent lesions via paracrine actions to drive the development of endometriosis, providing a rationale for translation into clinical practice and developing drugs for endometriosis.

The results showed that IL-6 may be an early low-grade chronic inflammatory marker among PCOS patients with IRS-2 polymorphism in Taiwanese population. This pharmacologic study in IRS-2 polymorphism may provide more information for preventing long-term complications in PCOS.