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Spermatogenesis is a complicated process that is tightly regulated by the well-coordinated expression of a series of genes in the testes. Ankyrin repeat domain-containing protein 49 (ANKRD49), an evolutionarily conserved protein highly expressed in the testes, is mainly found in spermatogonia, spermatocytes, and round spermatids. However, the exact function of ANKRD49 in spermatogenesis has remained elusive. In this study, we sought to investigate the role of ANKRD49 in apoptosis and determine the mechanism underlying this process in male germ cell-derived GC-1 cells. Nuclear staining with Hoechst 33258 and annexin V-FITC/PI, as well as analysis of caspase 3 activity, mitochondrial membrane potential, and apoptotic protein expression, showed that etoposide-induced apoptosis was attenuated by ANKRD49 overexpression but promoted by RNA interference-induced ANKRD49 knockdown. Furthermore, assessment of the levels of caspase 9, caspase 8, and proteins of the Bcl-2 family revealed ANKRD49 to be involved in an intrinsic apoptosis pathway. Examination of the subcellular distribution of the NF-κB p65 subunit after treatment with an NF-κB signaling inhibitor or p65 small interfering RNA demonstrated that ANKRD49 modulated etoposide-induced GC-1 cell apoptosis via the NF-κB pathway. Taken together, these results suggest that ANKRD49 plays an important role in reducing intrinsic apoptosis of GC-1 cells by modulating the NF-κB signaling pathway.

Di(n-butyl) phthalate (DBP) is extensively used in industrial applications as plasticizer and stabilizer and its presence in the environment may present health risks for human. Previous studies have demonstrated its mutagenic, teratogenic, and carcinogenic ability. However, its effect on mammalian oocyte maturation remains unknown. In this study, we examined the effect of DBP on oocyte maturation both in vitro and in vivo. Our results showed that DBP could significantly reduce mice oocyte germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) rates. In addition, oocyte cytoskeleton was damaged and cortical granule-free domains (CGFDs) were also disrupted. Finally, DBP induced early apoptosis of oocyte and granulosa cells (GCs). Collectively, these data demonstrate that DBP could reduce meiosis competence and mouse oocyte development., (Copyright © 2018. Published by Elsevier Ltd.)

Mancozeb, a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Mancozeb could lead to mitochondria dysfunction, cellular anti-oxidation enzymes depletion and apoptotic pathways activation. Previous studies indicated the exposure of mancozeb through mother would lead to irregular estrous cycles, decreased progesterone levels, reduced litter sizes, and more frequent delivery of dead fetuses. In this study, we investigated mancozeb inducing reproductive toxicity, especially focusing on its apoptotic effect and epigenetic modifications. We also showed that resveratrol, a kind of phytoalexin found in peanuts and grapes, can alleviate mancozeb's adverse effects, such as declined fertility, decreased ovary weight and primary follicles. Besides, mancozeb treated oocytes displayed suboptimal developmental competence and this can also be improved by treatment of resveratrol. More detailed investigation of these processes revealed that mancozeb increased reactive oxygen species, causing cell apoptosis and abnormal epigenetic modifications, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can alleviate mancozeb induced infertility and this was mainly through the correction of apoptotic tendency and the abnormity of cellular epigenetic modification.

Apoptosis, as an innate antiviral defense, not only functions to limit viral replication by eliminating infected cells, but also contribute to viral dissemination, particularly at the late stages of infection. A highly neurotropic CVS strain of rabies virus induces apoptosis both in vitro and in vivo. However, the detailed mechanism of CVS-mediated neuronal apoptosis is not entirely clear. Here, we show that CVS induces apoptosis through mitochondrial pathway by dissipating mitochondrial membrane potential, release of cytochrome c and AIF. CVS blocks Bax activation at the early stages of infection; while M protein partially targets mitochondria and induces mitochondrial apoptosis at the late stages of infection. The α-helix structure spanning 67-79 amino acids of M protein is essential for mitochondrial targeting and induction of apoptosis. These results suggest that CVS functions on mitochondria to regulate apoptosis at different stages of infection, so as to for viral replication and dissemination., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Perfluorooctane sulphonate (PFOS), as a surfactant, is widely applied in the agricultural production activities and has become a potential menace to human health. The mechanism of its effect on the maturation of mammalian oocytes is unclear. This study explored the toxic effect of PFOS on mouse oocyte maturation in vitro. The results revealed that PFOS under a concentration of 600 μM could significantly reduce the polar body extrusion rate (PBE) of mouse oocytes and cause symmetrical cell division. Further experiments showed that PFOS resulted in the abnormal cytoskeleton of the oocytes, causing the abnormal spindles and misplaced chromosomes, as well as the impaired dynamics of actin. Moreover, PFOS exposure inhibited the process of oocyte meiosis, which reflected in the slower spindle migration and continuous activation of spindle assembly checkpoint (SAC), then ultimately increased the probability of aneuploidy. Most importantly, PFOS exposure reduced the quality of oocytes, specifically by disrupting the function of mitochondria, inducing cell oxidative stress, and triggering early apoptosis. Furthermore, the level of methylation of histones is additionally influenced. In summary, our findings showed that PFOS exposure interfered with the maturation of mouse oocytes through affecting cytoskeletal dynamics, meiotic progression, oocyte quality, and histone modifications. [Display omitted] • PFOS of 600 μM has obvious toxic effects on mouse oocytes in vitro. • PFOS destroys the cytodynamic skeleton of mouse oocytes. • PFOS leads to oxidative stress and apoptosis induced by mitochondrial dysfunction. • PFOS inhibits the spindle migration and increases aneuploidy rate during meiosis. • PFOS alteres the expression of methylation modifier genes in mouse oocytes. [ABSTRACT FROM AUTHOR]

Two new platinum(II) complexes 7a and 7b with methyl hydrazinecarbodithioate derivatives of indolin-2-one have been prepared and characterized by single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometry. Antiproliferative activity of the two complexes and their ligands 6a and 6b against HCT-116, MCF-7 and MDA-MB-231 cell lines was determined by the MTS assay. Complexes 7a and 7b exhibited stronger antiproliferative activity against three cell lines than compounds 6a and 6b (IC 50 , 1.89–5.60 versus 6.52–35.13 μM). Moreover, treatment of HCT-116 cells with the complexes resulted in an obvious sub-G1 peak by cell cycle profile analysis, and an increase of cleaved PARP1 and caspases 3, 7, and 9 by immunoblotting analysis. Live cell imaging showed that nucleus shrinkage and condensation started to appear when MCF-7 cells were treated with 7a for 8 h. Fluorescent spectrophotometric analysis revealed that the complexes physically associated with calf thymus DNA. Competitive DNA binding assays uncovered that the complexes non-covalently bind to DNA. Taken together, our results indicated that the two new platinum(II) complexes 7a and 7b non-covalently bind to DNA with high affinity and exhibit cytotoxicity against cancer cells by inducing apoptosis. [ABSTRACT FROM AUTHOR]

Acrylonitrile is an organic chemical synthetic monomer that is widely used in food packaging and manufacturing. Animal studies have reported that acrylonitrile is carcinogenic and toxic, but the effects on the female reproductive function in mammals are unknown. In the present study, we report that acrylonitrile treatment affects ovarian homeostasis in mice, resulting in impaired follicular development. Follicles in acrylonitrile-exposed mice exhibited high levels of inflammation and apoptosis, and acrylonitrile treatment interfered with oocyte development. Transcriptomics analysis showed that acrylonitrile altered the expression of oocyte genes related to apoptosis, oxidative stress, endoplasmic reticulum stress, and autophagy. Further molecular tests revealed that acrylonitrile induced early apoptosis, DNA damage, elevated levels of reactive oxygen species, endoplasmic reticulum abnormalities, and lysosomal aggregation. We also observed disruption of mitochondrial structure and distribution and depolarization of membrane potential. Finally, acrylonitrile treatment in female mice decreased the number and weight of offspring. Altogether, these findings suggest that acrylonitrile impairs the stability of the ovarian internal environment, which in turn affects oocyte development and reduces the number of offspring. [Display omitted] • Acrylonitrile is toxic, but its effects on female reproductive function are unknown. • The work studies the effects of acrylonitrile on ovarian function and oocyte quality. • Inflammation and apoptosis are involved in acrylonitrile induced toxicity. [ABSTRACT FROM AUTHOR]

Captan is a non-systematic fungicide widely used in agricultural production, and its residues have been found in the environment and daily diet. Previous studies confirmed that captan exerts several toxic effects on tissues, but its effect on the mammalian female reproductive system is unclear. In current study, we reported that captan affected mouse ovarian homeostasis and disrupted female hormone receptor expression, leading to impaired follicular development. Ovarian follicles from the captan exposure group showed an increased level of inflammation, endoplasmic reticulum stress and apoptosis. In addition, captan exposure disrupted oocyte development. Transcriptomic analysis indicated that captan changed multiple genes expression in oocytes, including autophagy and apoptosis. Further molecular testing showed that captan induced oxidative stress and mitochondrial dysfunction, as indicated by the increased level of reactive oxygen species, disrupted mitochondrial structure and distribution, and depolarized membrane potential. Furthermore, captan triggered DNA damage, autophagy and early apoptosis, as shown by the enhanced levels of γ-H2AX, LC3, and Annexin-V and increased expression of related genes. Taken together, these results indicated that captan exposure impairs ovarian homeostasis and subsequently affects oocyte development. [Display omitted] • Captan exposure disrupted female hormone receptor expression and adversely affect follicle development. • Captan increased inflammation and apoptosis in ovarian follicle and altered the related gene expression. • Captan exposure triggered mitochondrial dys function and apoptosis, and blocked oocyte development. [ABSTRACT FROM AUTHOR]

[Display omitted] • PFDA exposure reduces GVBD and PBE rates of mouse oocytes. • PFDA exposure accelerates the PBE process, destroys the cytoskeleton, and increases aneuploidy. • PFDA exposure induces mitochondrial dysfunction, oxidative stress, and early apoptosis. • PFDA exposure alters epigenetic modifications. Perfluorodecanoic acid (PFDA) is a member of the perfluoroalkyl substances, which are toxic to organic functions. Recently, it has been found in follicular fluid, seriously interfering with reproduction. Follicular fluid provides the oocyte with necessary resources during the process of oocytes maturation. However, the effects of PFDA on the oocyte need investigation. Our study evaluated the impacts of PFDA on the meiosis and development potential of mouse oocytes by exposing oocytes to PFDA in vitro at 350, 400, and 450 μM concentrations. The results showed that exposure to PFDA resulted in the first meiotic prophase arrest by obstructing the function of the maturation-promoting factor. It also induced the dysfunction of the spindle assembly checkpoint, expedited the progression of the first meiotic process, and increased the risk of aneuploidy. The oocytes treated with PFDA had a broken cytoskeleton which also contributed to meiotic maturation failure. Besides, PFDA exposure caused mitochondria defections, increased the reactive oxygen species level in oocytes, and consequently induced oocyte apoptosis. Moreover, PFDA produced epigenetic modifications in oocytes and increased the frequency of mature oocytes with declined development potential. In summary, our data indicated that PFDA disturbs the meiotic process and induces oocyte quality deterioration. [ABSTRACT FROM AUTHOR]