Biology of Reproduction

It has been previously shown that the cytokine interleukin33 (IL33) is required for two processes, i.e. autophagic digestion of granulosa cells and recruitment of macrophages into atretic follicles, for full disposal of atretic follicles. Now, this study shows that activation of IL33-ST2 (IL33 receptor)-NFκB axis in granulosa in early atretic follicles may regulate those two events. Injection of hCG has been shown to induce a transient peak of IL33 expression with synchronized atresia. In this model, IL33-independent expression of ST2 in granulosa cells was detected in early atretic follicles before macrophage invasion...

Completion of fertilization is orchestrated by various ion channels in sperm membrane. Hyperpolarization of membrane potential, an indispensable event during the capacitation process, is dominated by sperm potassium channel (KSper). In addition to sperm-specific SLO3, which forms the channel pore, the auxiliary subunit leucine-rich-repeat-containing protein 52 (LRRC52) is required to form mKSper to function under physiological conditions. However, in human sperm, although most evidence supports that hSLO3 is the pore-forming subunit, whether hLRRC52 contributes to hKSper conductance and modulates sperm function remains to be understood...

It is known that the oocyte has a limited capacity to acquire and metabolize glucose, and it must rely on cumulus cells (CCs) to take up glucose and produce pyruvate for use to produce ATP through oxidative phosphorylation. We therefore propose that miRNAs might regulate glucose metabolism (GM) in CCs and might be used as markers for oocyte quality assessment. Here, mouse CC models with impaired glycolysis or pentose phosphate pathway (PPP) were established, and miRNAs targeting the key enzymes in glycolysis/PPP were predicted using the miRNA target prediction databases...

Chemically defined oocyte maturation media supplemented with FGF2, LIF and IGF-1 (FLI medium) enabled significantly improved oocyte quality in multiple farm animals, yet the molecular mechanisms behind such benefits were poorly defined. Here, we first demonstrated that FLI medium enhanced mouse oocyte quality assessed by blastocyst formation after in vitro fertilization, and implantation and fetal development after embryo transfer. We then analyzed the glucose concentrations in the spent media, ROS concentrations, mitochondrial membrane potential, spindle morphology in oocytes, and the abundance of transcripts of EGF-like factors, cumulus expansion factors, and glucose metabolism related genes in cumulus cells...

The centrosome is critical for maintaining the sperm head-tail connection and the formation of flagellar microtubules. In this study, we found that in mouse testes, coiled-coil domain-containing protein 159 (CCDC159) is specifically localized to the head-tail coupling apparatus (HTCA) of spermatids, a structure that ensures sperm head-tail tight conjunction. CCDC159 contains a C-terminal coiled-coil domain that functions as the centrosomal localization signal. Gene knockout (KO) of Ccdc159 in mice resulted in acephalic spermatozoa, abnormal flagella, and male infertility...

Defining features of Polycystic Ovary Syndrome (PCOS) include elevated expression of steroidogenic genes, theca cell androgen biosynthesis and peripheral levels of androgens. In previous studies we identified vascular cell adhesion molecule 1 (VCAM1) as a selective androgen target gene in specific NR2F2/SF1 (+/+) theca cells. By deleting NR2F2 and VCAM1 selectively in CYP17A1 theca cells in mice, we documented that NR2F2 and VCAM1 impact distinct and sometimes opposing theca cell functions that alter ovarian follicular development in vivo: including major changes in ovarian morphology, steroidogenesis, gene expression profiles, immunolocalization images (NR5A1, CYP11A1, NOTCH1, CYP17A1, INSL3, VCAM1, NR2F2) as well as granulosa cell functions...

Histones post-translational modifications (PTMs), such as phosphorylation, methylation, acetylation and ubiquitination, play vital roles in various chromatin-based cellular processes. Meiosis is crucial for organisms that depend on sexual reproduction to produce haploid gametes, during which chromatin undergoes intricate conformational changes. An increasing body of evidence is clarifying the essential roles of histone PTMs during meiotic divisions. In this review, we concentrate on the PTMs of H2A, H2B, H3 and H4 as well as the linker histone H1 that are required for meiosis and summarize recent progress in understanding how these modifications influence diverse meiotic events...

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Sperm proteins undergo post-translational modifications during sperm transit through the epididymis to acquire fertilizing ability. We previously reported that the genomic region coding Pate family genes is key to the proteolytic processing of the sperm membrane protein ADAM3 and male fertility. This region contains nine Pate family genes (Pate5-13), and two protein-coding genes (Gm27235 and Gm5916), with a domain structure similar to Pate family genes. Therefore, in this study, we aimed to identify key factors by narrowing the genomic region...

Uterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at approximately 30% of deliveries in the US and projected to continue to climb, a deeper understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are needed. Here we describe a rodent model of uterine injury on subsequent in utero outcomes...

The occurrence of unexplained recurrent spontaneous abortion (URSA) is closely related to immune system disorders, however, the underlying mechanisms remain unclear. The purpose of this study was to investigate the expression of GRIM-19 in URSA and the possible pathogenesis of URSA according to macrophage polarization. Here, we showed that GRIM-19 was downregulated in the uterine decidual macrophages of patients with URSA and that GRIM-19 downregulation was accompanied by increased M1 macrophage polarization...

Murine endogenous retrovirus with leucine tRNA primer, also known as MERVL, is expressed during zygotic genome activation in mammalian embryos. Here we show that protein arginine N-methyltransferase 6 (Prmt6) forms a chimeric transcript with MT2B2, one of the long terminal repeat sequences of MERVL, and is translated into an elongated chimeric protein (PRMT6MT2B2) whose function differs from that of the canonical PRMT6 protein (PRMT6CAN) in mouse preimplantation embryos. Overexpression of PRMT6CAN in fibroblast cells increased asymmetric dimethylation of the third arginine residue of both histone H2A (H2AR3me2a) and histone H4 (H4R3me2a), while overexpression of PRMT6MT2B2 increased only H2AR3me2a...

Cisplatin, a platinum-containing alkylating agent, is used in the treatment of various tumors owing to its potent antitumor activity. However, it causes permanent and adverse effects, particularly hearing loss and depletion of ovarian reserve. Until recently, there were no clinically available protective agents to mitigate the adverse side effects of cisplatin-induced cytotoxicity. In 2022, sodium thiosulfate (STS) was approved by the Food and Drug Administration for mitigating hearing loss in children and adolescents undergoing cisplatin treatment...

The Yangtze finless porpoises (YFP; Neophocaena asiaeorientalis a.) is an endemic and critically endangered species in China. Intensive captive breeding is essential for understanding the biology of critically endangered species, especially their pregnancy characteristics, knowledge of which is crucial for effective breeding management. Urine metabolomics can reveal metabolic differences, arising from physiological changes across pregnancy stages. Therefore, we used the urinary metabolomic technology, to explore urinary metabolite changes in pregnant YFPs...

New microscopy techniques in combination with tissue clearing protocols and emerging analytical approaches have presented researchers with the tools to understand dynamic biological processes in a three-dimensional context. This paves the road for the exploration of new research questions in reproductive biology, for which previous techniques have provided only approximate resolution. These new methodologies now allow for contextualized analysis of far larger volumes than was previously possible. Tissue optical clearing and three-dimensional imaging techniques posit the bridging of molecular mechanisms, macroscopic morphogenic development, and maintenance of reproductive function into one cohesive and comprehensive understanding of the biology of the reproductive system...

Vitamin D receptors (VDR) and vitamin D3 metabolizing enzymes have been found to be highly expressed in the ovaries and spermatophores of fish. However, the role of VD3 on fish gonadal development has rarely been reported. In this study, two-month-old female zebrafish were fed with different concentrations of VD3 diets (0 IU/kg, 700 IU/kg, 1400 IU/kg, and 11,200 IU/kg) to investigate the effects of VD3 on ovarian development. The diet with 0 IU/kg VD3 resulted in elevated interstitial spaces, follicular atresia and reproductive toxicity in zebrafish ovaries...

Maternal immune activation during pregnancy is a risk factor for offspring neuropsychiatric disorders. Among the mechanistic pathways by which maternal inflammation can affect fetal brain development and programming, those involving tryptophan (TRP) metabolism have drawn attention because various TRP metabolites have neuroactive properties. This study evaluates the effect of bacterial (LPS) and viral (poly I:C) placental infection on TRP metabolism using an ex vivo model. Human placenta explants were exposed to LPS or Poly I:C, and the release of TRP metabolites was analyzed together with the expression of related genes and proteins and the functional activity of key enzymes in TRP metabolism...

Protein kinase A (PKA) signaling pathway which mediated protein phosphorylation is important for sperm motility and male fertility. This process relies on A-kinase anchoring proteins (AKAPs) that organize PKA and its signalosomes within specific subcellular compartments. Previously, it was found that the absence of AKAP3 leads to multiple morphological abnormalities in mouse sperm. But how AKAP3 regulates sperm motility is yet to be elucidated. AKAP3 has two amphipathic domains, Dual and RI in its N-terminus...

Studying testicular genes´ expression may give key insights into precise regulation of its functions that influence epididymal sperm quality. The current study aimed to investigate the abundance of candidate genes involved in the regulation of testicular functions specially those regulate sperm function (PLA2G4D, SPP1 and CLUAP1), testicular steroidogenic function (ESR1 and AR), materials transport (AQP12B and LCN15) and defense mechanisms (DEFB110, GPX5, SOCS3 and IL6). Therefore, blood samples and testes with epididymis were collected from mature middle-aged (5-10 years) dromedary camels (n = 45) directly prior and after their slaughtering, respectively, during breeding season...

Di(2-ethylhexyl) phthalate (DEHP) is a pervasive environmental toxicant used in the manufacturing of numerous consumer products, medical supplies, and building materials. DEHP is metabolized to mono(2-ethylhexyl) phthalate (MEHP). MEHP is an endocrine disruptor that adversely affects folliculogenesis and steroidogenesis in the ovary, but its mechanism of action is not fully understood. Thus, we tested the hypothesis that the aryl hydrocarbon receptor (AHR) plays a functional role in MEHP-mediated disruption of folliculogenesis and steroidogenesis...