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IRE1α, a type I transmembrane protein characterized by a cytoplasmic serine/threonine kinase domain, is related to ER stress and ER function maintenance. In this study, 4µ8c, a highly effective selective inhibitor of IRE1α RNase, and APY29, an ATP competitive inhibitor, inhibiting IRE1α autophosphorylation and the kinase domain, were employed to elucidate the function of IRE1α on the proliferation of ovarian granulosa cells, with the ultimate goal of identifying novel strategies and methodologies for the prevention and treatment of associated diseases. Human ovarian granulosa cells (SVOG) cultured in vitro were treated with the IRE1α inhibitors 4µ8c and APY29. It was shown that inhibition of IRE1α reduced the cell ability of dealing with misfolded protein, triggered oxidative stress, altered mitochondrial membrane potential, and inflicted DNA damage, eventually lead to ovarian granulosa cell apoptosis.
IRE1α, a type I transmembrane protein characterized by a cytoplasmic serine/threonine kinase domain, is related to ER stress and ER function maintenance. In this study, 4µ8c, a highly effective selective inhibitor of IRE1α RNase, and APY29, an ATP competitive inhibitor, inhibiting IRE1α autophosphorylation and the kinase domain, were employed to elucidate the function of IRE1α on the proliferation of ovarian granulosa cells, with the ultimate goal of identifying novel strategies and methodologies for the prevention and treatment of associated diseases. Human ovarian granulosa cells (SVOG) cultured in vitro were treated with the IRE1α inhibitors 4µ8c and APY29. It was shown that inhibition of IRE1α reduced the cell ability of dealing with misfolded protein, triggered oxidative stress, altered mitochondrial membrane potential, and inflicted DNA damage, eventually lead to ovarian granulosa cell apoptosis.
BackgroundThe management of Non-Obstructive (NOA) Azoospermia or Obstructive Azoospermia (OA) patients relies on testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI). In NOA patients the sperm recovery is successful in only 50% of cases and therefore the ability to predict those patients with a high probability of achieving a successful sperm retrieval would be a great value in counselling the patient and his partner. Several studies tried to suggest predictors of a positive TESE (e.g. FSH concentration), but most concluded that diagnostic testicular biopsy (histology) is best.MethodsThis is a retrospective analysis of 526 TESE patients. After the extraction of the testis, the resulting sample was immediately given to the embryologist, who examined the tubules for sperm cryopreservation. During the same procedure, a different specimen was destined to the histological analysis. The comparison between the two methodological approaches was carried out through a score.ResultsConcordance between TESE and testicular histology outcomes was found in 70,7% of patients; discordance was found in 29,3% of patients. Among the discordance outcomes, in approximately 95% we found at least 1 sperm in the TESE retrieval, while the histology report did not find any spermatozoa or found not enough compared to our evaluation; in only 5% of cases we did not find any spermatozoa or found not enough compared to what was detected in the testicular histology.ConclusionBased on our experience, to increase diagnostic accuracy, a larger biopsy should be sent to the histopathology laboratory; another option may be to use TESE cell suspension (the same embryologists employ for cryopreservation) for cytological evaluation of spermatogenesis.
Autophagy, an evolutionarily conserved cellular mechanism essential for maintaining internal stability, plays a crucial function in female reproductive ability. In this review, we discuss the complex interplay between autophagy and several facets of female reproductive health, encompassing pregnancy, ovarian functions, gynecologic malignancies, endometriosis, and infertility. Existing research emphasizes the crucial significance of autophagy in embryo implantation, specifically in the endometrium, highlighting its necessity in ensuring proper fetal development. Although some knowledge has been gained, there is still a lack of research on the specific molecular impacts of autophagy on the quality of oocytes, the growth of follicles, and general reproductive health. Autophagy plays a role in the maturation, quality, and development of oocytes. It is also involved in reproductive aging, contributing to reductions in reproductive function that occur with age. This review explores the physiological functions of autophagy in the female reproductive system, its participation in reproductive toxicity, and its important connections with the endometrium and embryo. In addition, this study investigates the possibility of emerging treatment approaches that aim to modify autophagy, using both natural substances and synthetic molecules, to improve female fertility and reproductive outcomes. Additionally, this review intends to inspire future exploration into the intricate role of autophagy in female reproductive health by reviewing recent studies and pinpointing areas where current knowledge is lacking. Subsequent investigations should prioritize the conversion of these discoveries into practical uses in the medical field, which could potentially result in groundbreaking therapies for infertility and other difficulties related to reproduction. Therefore, gaining a comprehensive understanding of the many effects of autophagy on female fertility would not only further the field of reproductive biology but also open new possibilities for diagnostic and treatment methods.
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