Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.

Retinal neurodegeneration (RN), an early marker of diabetic retinopathy (DR), is closely associated with Müller glia cells (MGs) in diabetic subjects. MGs play a pivotal role in maintaining retinal homeostasis, integrity, and metabolic support and respond to diabetic stress. In lower vertebrates, MGs have a strong regenerative response and can completely repair the retina after injuries.

LH promotes the proliferation of porcine primordial germ cell-like cells (pPGCLCs) by regulating the ceRNA network related to the TGF-β signaling pathway.

Primordial germ cells (PGCs), as the precursors of gametes found in early embryos, provide a new direction for solving the problem of reproductive disorders. In vitro, conversion of adult stem cells (ASCs) into primordial germ cell-like cells (PGCLCs) is feasible. The means of increasing PGCLCs number in vitro has been a focus of recent stem cell research.

Gonadotropin Activity during Early Folliculogenesis and Implications for Polycystic Ovarian Syndrome and Premature Ovarian Insufficiency: A Narrative Review.

Female fertility depends on the ovarian reserve of follicles, which is determined at birth. Primordial follicle development and oocyte maturation are regulated by multiple factors and pathways and classified into gonadotropin-independent and gonadotropin-dependent phases, according to the response to gonadotropins. Folliculogenesis has always been considered to be gonadotropin-dependent only from the antral stage, but evidence from the literature highlights the role of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during early folliculogenesis with a potential role in the progression of the pool of primordial follicles.

RNA m6A dynamic modification mediated by nucleus-localized FTO is involved in follicular reserve.

In eukaryotic organisms, the most common internal modification of messenger RNA (mRNA) is N6-methyladenosine (m6A). This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers. The fat-mass and obesity-associated protein (FTO) catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes.

Aflatoxin B1 affects porcine alveolar macrophage growth through the calcium signaling pathway mediated by the ceRNA regulatory network.

Background: Aflatoxin B1 (AFB1), one of the most prevalent contaminants in human and animal food, impairs the immune system, but information on the mechanisms of AFB1-mediated macrophage toxicity is still lacking.

Methods And Results: In this study, for the first time, we employed whole transcriptome sequencing technology to explore the molecular mechanism by which AFB1 affects the growth of porcine alveolar macrophages (PAM). We found that AFB1 exposure reduced the proliferative capacity of PAM and prevented cell cycle progression.

Reprogramming Human Female Adipose Mesenchymal Stem Cells into Primordial Germ Cell-Like Cells.

In the last two decades, considerable progress has been made in the derivation of mammalian germ cells from pluripotent stem cells such as Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs). The pluripotent stem cells are generally first induced into pre-gastrulating endoderm/mesoderm-like status and then specified into putative primordial germ cells (PGCs) termed PGC-like cells (PGCLCs) which possess the potential to generate oocytes and sperms. Adipose-derived mesenchymal stromal cells (ASCs) are multipotent cells, having the capacity to differentiate into cell types such as adipocytes, osteocytes and chondrocytes.

Naringin regulates intestinal microorganisms and serum metabolites to promote spermatogenesis.

Naringin (NAR) is a dihydroflavonoid with various biological activities and pharmacological effects, especially natural antioxidant activity. To gain a better understanding of the effects of NAR on the reproductive system, especially spermatogenesis, we employed western blotting, immunofluorescence, immunohistochemistry, metabolomics and microbiomics to comprehensively dissect the impact of NAR on spermatogenesis. NAR promotes germ cell proliferation and testicular development, and promotes the secretion of sex hormones.

Inheritance of perturbed methylation and metabolism caused by uterine malnutrition via oocytes.

Background: Undernourishment in utero has deleterious effects on the metabolism of offspring, but the mechanism of the transgenerational transmission of metabolic disorders is not well known. In the present study, we found that undernourishment in utero resulted in metabolic disorders of female F1 and F2 in mouse model.

Results: Undernutrition in utero induced metabolic disorders of F1 females, which was transmitted to F2 females.

Analysis of Secreted Proteins from Prepubertal Ovarian Tissues Exposed In Vitro to Cisplatin and LH.

It is well known that secreted and exosomal proteins are associated with a broad range of physiological processes involving tissue homeostasis and differentiation. In the present paper, our purpose was to characterize the proteome of the culture medium in which the oocytes within the primordial/primary follicles underwent apoptosis induced by cisplatin (CIS) or were, for the most part, protected by LH against the drug. To this aim, prepubertal ovarian tissues were cultured under control and in the presence of CIS, LH, and CIS + LH.

The process of ovarian aging: it is not just about oocytes and granulosa cells.

Ovarian age is classically considered the main cause of female reproductive infertility. In women, the process proceeds as an ongoing decline in the primordial follicle stockpile and it is associated with reduced fertility in the mid-thirties, irregular menstruation from the mid-forties, cessation of fertility, and, eventually, menopause in the early fifties. Reproductive aging is historically associated with changes in oocyte quantity and quality.

The ovarian reserve as target of insulin/IGF and ROS in metabolic disorder-dependent ovarian dysfunctions.

Unlabelled: It is known for a long time that metabolic disorders can cause ovarian dysfunctions and affect a woman's fertility either by direct targeting follicular cells and/or the oocytes or by indirect interference with the pituitary-hypothalamic axis, resulting in dysfunctional oogenesis. Such disorders may also influence the efficiency of the embryo implantation and the quality of the embryo with permanent effects on the fertility and health of the offspring. Thanks to the expanding knowledge on the molecular mechanisms governing oogenesis and folliculogenesis in mammals, we are beginning to understand how such disorders can negatively affect this process and consequently fertility in women.

Human adipose-derived stromal cells transplantation prolongs reproductive lifespan on mouse models of mild and severe premature ovarian insufficiency.

Background: Although recent studies have investigated the ability of Mesenchymal Stromal Cells (MSCs) to alleviate short-term ovarian damage in animal models of chemotherapy-induced Premature Ovarian Insufficiency (POI), no data are available on reproductive lifespan recovery, especially in a severe POI condition. For this reason, we investigated the potential of MSCs isolated from human adipose tissue (hASCs), since they are easy to harvest and abundant, in ameliorating the length and performance of reproductive life in both mild and severe chemotherapy-induced murine POI models.

Methods: Mild and severe POI models were established by intraperitoneally administering a light (12 mg/kg busulfan + 120 mg/kg cyclophosphamide) or heavy (30 mg/kg busulfan + 120 mg/kg cyclophosphamide) dose of chemotherapy, respectively, in CD1 mice.

YAP regulates porcine skin-derived stem cells self-renewal partly by repressing Wnt/β-catenin signaling pathway.

Skin-derived stem cells (SDSCs) are a class of adult stem cells (ASCs) that have the ability to self-renew and differentiate. The regulation mechanisms involved in the differentiation of SDSCs are a hot topic. In this paper, we explore the link between the transcriptional regulator yes-associated protein (YAP) and the fate of porcine SDSCs (pSDSCs).

PI3K/PTEN/AKT Signaling Pathways in Germ Cell Development and Their Involvement in Germ Cell Tumors and Ovarian Dysfunctions.

Several studies indicate that the PI3K/PTEN/AKT signaling pathways are critical regulators of ovarian function including the formation of the germ cell precursors, termed primordial germ cells, and the follicular pool maintenance. This article reviews the current state of knowledge of the functional role of the PI3K/PTEN/AKT pathways during primordial germ cell development and the dynamics of the ovarian primordial follicle reserve and how dysregulation of these signaling pathways may contribute to the development of some types of germ cell tumors and ovarian dysfunctions.

Protective Mechanism of Luteinizing Hormone and Follicle-Stimulating Hormone Against Nicotine-Induced Damage of Mouse Early Folliculogenesis.

Previous studies have shown that nicotine could impair the germ cell cyst breakdown and the primordial follicle assembly by autophagy. In this paper, we discovered that luteinizing hormone (LH) and follicle-stimulating hormone (FSH) could counteract the damage caused by nicotine of mouse germ cell cyst breakdown. The neonatal mice were separately intraperitoneally injected with nicotine, nicotine plus LH, nicotine plus FSH, and saline (control) for 4 days.

To Be or Not to Be a Germ Cell: The Extragonadal Germ Cell Tumor Paradigm.

In the human embryo, the genetic program that orchestrates germ cell specification involves the activation of epigenetic and transcriptional mechanisms that make the germline a unique cell population continuously poised between germness and pluripotency. Germ cell tumors, neoplasias originating from fetal or neonatal germ cells, maintain such dichotomy and can adopt either pluripotent features (embryonal carcinomas) or germness features (seminomas) with a wide range of phenotypes in between these histotypes. Here, we review the basic concepts of cell specification, migration and gonadal colonization of human primordial germ cells (hPGCs) highlighting the analogies of transcriptional/epigenetic programs between these two cell types.

Effects of low-dose X-ray medical diagnostics on female gonads: Insights from large animal oocytes and human ovaries as complementary models.

Diagnostic imaging has significantly grown over the last thirty years as indispensable support for diagnostic, prognostic, therapeutic and monitoring procedures of human diseases. This study explored the effects of low-dose X-ray medical diagnostics exposure on female fertility. To aim this, cumulus-oocyte complexes (COCs) recovered from the ovaries of juvenile sheep and human ovaries were used as complementary models for in vitro studies.

The p63 C-terminus is essential for murine oocyte integrity.

The transcription factor p63 mediates distinct cellular responses, primarily regulating epithelial and oocyte biology. In addition to the two amino terminal isoforms, TAp63 and ΔNp63, the 3'-end of p63 mRNA undergoes tissue-specific alternative splicing that leads to several isoforms, including p63α, p63β and p63γ. To investigate in vivo how the different isoforms fulfil distinct functions at the cellular and developmental levels, we developed a mouse model replacing the p63α with p63β by deletion of exon 13 in the Trp63 gene.

miR-378-3p maintains the size of mouse primordial follicle pool by regulating cell autophagy and apoptosis.

Primordial follicle pool provides all available oocytes throughout the whole reproductive life span. Abnormal regulation in primordial follicle assembly leads to abnormal size of primordial follicle pool, even causes infertility. Here, miR-378-3p was proved to regulate mouse primordial follicle assembly both in vivo and in vitro.

IUI and uterine lavage of in vivo-produced blastocysts for PGT purposes: is it a technically and ethically reasonable perspective? Is it actually needed?

A recent study by Munné et al. portrayed a protocol to retrieve in vivo produced blastocysts after IUI and uterine lavage for preimplantation genetic testing (PGT) purposes. The authors claimed this protocol might represent a reasonable future perspective for patients who do not want to undergo IVF, but still want to be informed about their embryos' genetic/chromosomal defects.