Female infertility is mainly caused by ovulation disorders, which affect female reproduction and pregnancy worldwide, with polycystic ovary syndrome (PCOS) being the most prevalent of these. PCOS is a frequent endocrine disease that is associated with abnormal function of the female sex hormone estrogen and estrogen receptors (ERs). Estrogens mediate genomic effects through ERα and ERβ in target tissues. The G-protein-coupled estrogen receptor (GPER) has recently been described as mediating the non-genomic signaling of estrogen. Changes in estrogen receptor signaling pathways affect cellular activities, such as ovulation; cell cycle phase; and cell proliferation, migration, and invasion. Over the years, some selective estrogen receptor modulators (SERMs) have made substantial strides in clinical applications for subfertility with PCOS, such as tamoxifen and clomiphene, however the role of ER in PCOS still needs to be understood. This article focuses on the recent progress in PCOS caused by the abnormal expression of estrogen and ERs in the ovaries and uterus, and the clinical application of related targeted small-molecule drugs.

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 μmol/L vs. 325.60 ± 18.65 μmol/L, p < 0.001), serum creatinine (66.20 ± 11.88 μmol/L vs. 182.20 ± 8.87 μmol/L, p < 0.001) and BUN level (13.33 ± 3.16 mmol/L vs. 36.04 ± 6.60 mmol/L, p < 0.001). The treatment group also displayed attenuated renal pathological lesions and metabolic endotoxemia (25.60 ± 5.90 ng/mL vs. 38.40 ± 4.98 ng/mL, p < 0.01), and improved tightly linked proteins expression. Besides, curcumin altered the gut microbiota structure in UAN rats. More specifically, curcumin treatment protected against the overgrowth of opportunistic pathogens in UAN, including Escherichia-Shigella and Bacteroides, and increased the relative abundance of bacteria producing short‐chain fatty acids (SCFAs), such as Lactobacillus and Ruminococcaceae. These results suggest that curcumin could modulate gut microbiota, fortify the intestinal barrier, attenuate metabolic endotoxemia, and consequently protect the renal function in UAN rats.

Cell lineage tracing is a key technology for describing the developmental history of individual progenitor cells and assembling them to form a lineage development tree. However, traditional methods have limitations of poor stability and insufficient resolution. As an efficient and flexible gene editing tool, CRISPR‐Cas9 system has been widely used in biological research. Furthermore, CRISPR‐Cas9 gene editing‐based tracing methods can introduce fluorescent proteins, reporter genes, or DNA barcodes for high‐throughput sequencing, enabling precise lineage analysis, significantly improving precision and resolution, and expanding its application range. In this review, we summarize applications of CRISPR‐Cas9 system in cell lineage tracing, with special emphasis on its successful applications in traditional model animals (e.g., zebrafish and mice), large animal models (pigs), and human cells or organoids. We also discussed its potential prospects and challenges in xenotransplantation and regenerative medicine.

Fibroblast growth factor 5 (FGF5) plays key roles in promoting the transition from the anagen to catagen during the hair follicle cycle. The sheep serves as an excellent model for studying hair growth and is frequently utilized in various research processes related to human skin diseases. We used the CRISPR/Cas9 system to generate four FGF5-edited Dorper sheep and only low levels of FGF5 were detected in the edited sheep. The density of fine wool in GE sheep was markedly increased, and the proportion of fine wool with a diameter of 14.4–20.0 μm was significantly higher. The proliferation signal in the skin of gene-edited (GE) sheep was stronger than in wild-type (WT) sheep. FGF5 editing decreased cortisol concentration in the skin, further activated the activity of antioxidant enzymes such as Glutathione peroxidase (GSH-Px), and regulated the expression of Wnt signaling pathways containing Wnt agonists (Rspondins, Rspos) and antagonists (Notum) in hair regeneration. We suggest that FGF5 not only mediates the activation of antioxidant pathways by cortisol, which constitutes a highly coordinated microenvironment in hair follicle cells, but also influences key signals of the Wnt pathway to regulate secondary hair follicle (SHF) development. Overall, our findings here demonstrate that FGF5 plays a significant role in regulating SHF growth in sheep and potentially serves as a molecular marker of fine wool growth in sheep breeding.

Stingers, evolved from ovipositors, are an important defense organ for the Apidae, Vespidae, and Formicidae species. However, the molecular mechanism of stinger development remains unclear. Here, we show that the earliest time point for the appearance of stingers in Apis mellifera is at the 1-day-old worker pupal stage based on morphological observations and anatomy from the pre-pupal to adult stages. To discover the genes related to stinger development, we first comprehensively compared the stinger transcriptome at different stages and screened 1282, 186, and 166 highly expressed genes in the stingers of 1- and 5-day-old worker pupae and newly emerged worker bees (NEBs), respectively, then identified 25 DEGs involved in the early stage of stinger development. We found that Dll was a key candidate gene in the early development of A. mellifera stingers by combining analyses of the protein–protein interaction network and spatiotemporal expression patterns. An RNAi experiment showed that about 20% of individuals exhibited tip bending in the piercing parts of their stingers in the Dll-dsRNA-treated group, with the morphology presenting as side–side or front–back tip bending. This indicates that Dll plays a vital role in the early development of A. mellifera stingers. Together, our study provides insight into the molecular mechanism of Hymenoptera stinger development and an inspiration for the molecular breeding of gentle honeybee species with stinger abnormalities.

The appetite of honeybees for food is crucial to their survival and reproduction, as they sustain their entire colony by collecting pollen and nectar for nutrients. Dopamine, an important neurotransmitter, regulates appetite and satiety. However, how dopamine regulates honeybee foraging behavior remains unexplored. In this study, we investigated dopamine expression in 23-day-old Apis mellifera under different food-wanting conditions and identified differentially expressed genes (DEGs) in the brains of honeybees using RNA sequencing technology. We showed that dopamine levels in honeybees starved for 2 h were higher than those sated after 2 h of starvation. RNA-seq results revealed there were differences in the expression of cytochrome P450-dependent monooxygenase (CYP9Q1) in honeybees, which regulated the sucrose sensitivity of honeybees under different intake states. Furthermore, CYP9Q1 targeted the expression of the insulin receptor substrate (IRS) to promote dopamine synthesis. Our findings emphasize the relationship between dopamine and honeybees’ desire for food at the molecular level, providing a reference for further exploring the mechanism of food wanting.