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Protein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found that PRMT5 was expressed at high level in ovarian granulosa cells of growing follicles. Inactivation of Prmt5 in granulosa cells resulted in aberrant follicle development and female infertility. In Prmt5-knockout mice, follicle development was arrested with disorganized granulosa cells in which WT1 expression was dramatically reduced and the expression of steroidogenesis-related genes was significantly increased. The premature differentiated granulosa cells were detached from oocytes and follicle structure was disrupted. Mechanism studies revealed that Wt1 expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation of Wt1 mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes in Prmt5-deficient granulosa cells was repressed by Wt1 overexpression. These results demonstrate that PRMT5 participates in granulosa cell lineage maintenance by inducing Wt1 expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development., eLife digest Infertility in women can be caused by many factors, such as defects in the ovaries. An important part of the ovaries for fertility are internal structures called follicles, which house early forms of egg cells. A follicle grows and develops until the egg is finally released from the ovary into the fallopian tube, where the egg can then be fertilised. In the follicle, an egg is surrounded by other types of cells, such as granulosa cells. The egg and neighbouring cells must maintain healthy contacts with each other, otherwise the follicle can stop growing and developing, potentially causing infertility. The development of a follicle depends on an array of proteins. For example, the transcription factor WT1 controls protein levels by activating other genes and their proteins and is produced in high numbers by granulosa cells at the beginning of follicle development. Although WT1 levels dip towards the later stages of follicle development, insufficient levels can lead to defects. So far, it has been unclear how levels of WT1in granulose cells are regulated. Chen, Dong et al. studied mouse follicles to reveal more about the role of WT1 in follicle development. The researchers measured protein levels in mouse granulosa cells as the follicles developed, and discovered elevated levels of PRMT5, a protein needed for egg cells to form and survive in the follicles. Blocking granulosa cells from producing PRMT5 led to abnormal follicles and infertility in mice. Moreover, mice that had been engineered to lack PRMT5 developed abnormal follicles, where the egg and surrounding granulosa cells were not attached to each other, and the granulosa cells had low levels of WT1. Further experiments revealed that PRMT5 controlled WT1 levels by adding small molecules called methyl groups to another regulatory protein called HnRNPA1. The addition of methyl groups to genes or their proteins is an important modification that takes place in many processes within a cell. Chen, Dong et al. reveal that this activity also plays a key role in maintaining healthy follicle development in mice, and that PRMT5 is necessary for controlling WT1. Identifying all of the intricate mechanism involved in regulating follicle development is important for finding ways to combat infertility.

Arginine methylation is one of the most important post-translational modifications which is catalyzed by protein arginine methyltransferases (PRMTs). Previous studies have demonstrated that Prmt5 plays important role in germ cell development. Prmt7 is the only family member responsible for mono-methylation of arginine residue. However, whether Prmt7 is also involved in germ cell development remains unclear. In this study, we find that PRMT7 is abundantly expressed in the male germ cells during embryonic stage (from E10.5). Depletion of Prmt7 results in the defect of germ cell proliferation during embryonic stage and the number of primordial germ cells is significantly reduced in Prmt7-/- mice at E11.5. We also find that the size of testes is reduced in Prmt7-/- mice at P5 with reduced germ cell number and the diameter of seminiferous tubules. Further study reveals that the expression of BMPs and TGF-β singling pathway is significantly changed in germ cells of Prmt7-/- mice at E12.5. However, no defect of testes development is observed in adult Prmt7-/flox; Mvh-Cre mice. Collectively, this study demonstrates that Prmt7 plays roles in male germ cell proliferation during embryonic stages and it is not required for germ cell development postnatally.

Advanced oxidation processes (AOPs) are effective ways to degrade refractory organic contaminants, relying on the generation of inorganic radicals (e.g., &bull, OH and SO4&bull, &minus, ). Herein, a novel AOP with organic radicals (R-O&bull, ) was reported to degrade contaminants. Lanthanum cobaltite perovskite (LaCoO3) was used to activate peracetic acid (PAA) for organic radical generation to degrade sulfamethoxazole (SMX). The results show that LaCoO3 exhibited an excellent performance on PAA activation and SMX degradation at neutral pH, with low cobalt leaching. Meanwhile, LaCoO3 also showed an excellent reusability during PAA activation. In-depth investigation confirmed CH3C(O)O&bull, and CH3C(O)OO&bull, as the key reactive species for SMX degradation in LaCoO3/PAA system. The presence of Cl&minus, (1&ndash, 100 mM) slightly inhibited the degradation of SMX in the LaCoO3/PAA system, whereas the addition of HCO3&minus, (0.1&ndash, 1 mM) and humic aid (1&ndash, 10 mg/L) could significantly inhibit SMX degradation. This work highlights the generation of organic radicals via the heterogeneous activation of PAA and thus provides a promising way to destruct contaminants in wastewater treatment.

As an emerging light source, ultraviolet light emitting diodes (UV-LEDs) are adopted to overcome the shortcomings of the conventional mercury lamp, such as mercury pollution. The degradation of chloramphenicol (CAP) using three UV-LED-based advanced oxidation processes (AOPs)—UV-LED/persulfate (UV-LED/PS), UV-LED/peroxymonosulfate (UV-LED/PMS) and UV-LED/chlorine—was investigated. Results indicate that CAP can be more effectively degraded by the hybrid processes when compared to UV irradiation and oxidants alone. Degradation of CAP using the three UV-LED-based AOPs followed pseudo-first-order kinetics. The degradation rate constants (kobs) for UV-LED/PS, UV-LED/PMS, and UV-LED/chlorine were 0.0522, 0.0437 and 0.0523 min−1, and the CAP removal rates 99%, 98.1% and 96.3%, respectively. The degradation rate constant (kobs) increased with increasing oxidant dosage for UV-LED/chlorine, whereas overdosing reduced CAP degradation using UV-LED/PS and UV-LED/PMS. Ultraviolet wavelength influenced degradation efficiency of the UV-LED based AOPs with maximum CAP degradation observed at a wavelength of 280 nm. The application of UV-LED enhanced the formation DBPs during subsequent chlorination. uUV-LED/PMS produced more disinfection by-products than UV-LED/PS. Compared to UV-LED, UV-LED/PS reduced the formation of dichloroacetonitrile and trichloronitromethane during chlorination owing to its capacity to degrade the nitro group in CAP. The intermediates dichloroacetamide, 4-nitrobenzoic acid, 4-nitrophenol were produced during the degradation of CAP using each of UV-LED, UV-LED/PS and UV-LED/chlorine. The present study provides further evidence supporting the application of UV-LED in AOPs.

The interaction between germ cell and somatic cell plays important roles in germ cell development. However, the exact function of gonad somatic cell in germ cell differentiation is unclear. In the present study, the function of gonad somatic cell in germ cell meiosis was examined by using mouse models with aberrant somatic cell differentiation. In Wt1R394W/R394W mice, the genital ridge is absent due to the apoptosis of coelomic epithelial cells. Interestingly, in both male and female Wt1R394W/R394W germ cells, STRA8 was detected at E12.5 and the scattered SYCP3 foci were observed at E13.5 which was consistent with control females. In Wt1-/flox; Cre-ERTM mice, Wt1 was inactivated by the injection of tamoxifen at E9.5 and the differentiation of Sertoli and granulosa cells was completely blocked. We found that most germ cells were located outside of genital ridge after Wt1 inactivation. STRA8, SYCP3, and γH2AX proteins were detected in germ cells of both male and female Wt1-/flox; Cre-ERTM gonads, whereas no thread-like SYCP3 signal was observed. Our study demonstrates that aberrant development of gonad somatic cells leads to ectopic expression of meiosis-associated genes in germ cells, but meiosis was arrested before prophase I. These results suggest that the proper differentiation of gonad somatic cells is essential for germ cell meiosis.

The rice field eel Monopterus albus is a hermaphroditic protogynous fish species that undergoes sex reversal from female to male. However, the potential mechanisms underlying the process of sex transformation are still unclear. We analyzed and compared the gene sequence of M. albus dmrt1 5′ upstream region and its potential transcription factor binding sites with other known species and examined the in vitro effects of testosterone (T) on the expression levels of dmrt1a and foxl2 in the ovotestis. Moreover, we cloned and analyzed the expression of genes encoding enzymes, 11β-hydroxylase (11β-h) and 11β-hydroxysteroid dehydrogenase (11β-hsd), involved in the production of 11-ketotestosterone (11-KT). The results showed that, compared with other fish species, M. albus dmrt1 5′ upstream region contained unique androgen response elements (AREs) with one on the sense strand and the other one on the antisense strand, indicating a crucial role for androgens in the transcriptional regulation of dmrt1. The expression of dmrt1a was induced but the expression of foxl2 was inhibited by T manipulation in vitro, suggesting that blood androgen could activate the transcription of dmrt1 in the ovotestis. Moreover, the expression levels of 11β-h and 11β-hsd2 were predominantly expressed in testis, much less in ovotestis, and barely in ovary, suggesting the production of 11-KT during sex reversal. Androgens are synthesized in large amounts during sex reversal, leading to the promotion of dmrt1 transcription, and thus, gonadal somatic cells transdifferetiation. Overall, androgen-dmrt1 positive feedback programs the M. albus sex reversal.

Synapses are semi-membraneless, protein-dense, sub-micron chemical reaction compartments responsible for signal processing in each and every neuron. Proper formation and dynamic responses to stimulations of synapses, both during development and in adult, are fundamental to functions of mammalian brains, although the molecular basis governing formation and modulation of compartmentalized synaptic assemblies is unclear. Here, we used a biochemical reconstitution approach to show that, both in solution and on supported membrane bilayers, multivalent interaction networks formed by major excitatory postsynaptic density (PSD) scaffold proteins led to formation of PSD-like assemblies via phase separation. The reconstituted PSD-like assemblies can cluster receptors, selectively concentrate enzymes, promote actin bundle formation, and expel inhibitory postsynaptic proteins. Additionally, the condensed phase PSD assemblies have features that are distinct from those in homogeneous solutions and fit for synaptic functions. Thus, we have built a molecular platform for understanding how neuronal synapses are formed and dynamically regulated.