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Triptolide (TPL), a prominent bioactive constituent derived from the Chinese herb Tripterygium wilfordii, exhibits diverse pharmacological effects such as anti-tumor and anti-immune properties. Despite its extensive clinical application for the treatment of arthritis and immune disorders, TPL has been associated with multiorgan toxicity, including adverse effects on the female reproductive system. However, the precise mechanisms underlying TPL-induced ovarian damage remain poorly understood. In this study, employing a mouse toxicological model, exposure to TPL was observed to result in decreased ovarian coefficient and fertility. Subsequent research demonstrated TPL exposure affected mitochondrial function, increased mitochondrial outer membrane permeability, resulted in mtDNA releasing into the cytoplasm. These events subsequently activated cGAS-STING pathway, leading to ovarian inflammation. Furthermore, TPL exposure has been found to disrupt the meiotic maturation of oocytes, which is mechanistically associated with suboptimal morphology of spindle and microtubule organizing centers (MTOCs). This association has been further confirmed through the use of reduced representation bisulfite sequencing (RRBS). In conclusion, our study demonstrates that TPL exposure can hinder follicular development, resulting in ovarian inflammation and reduced oocyte quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Women with polycystic ovary syndrome (PCOS) are characterized by endocrine disorders accompanied by a decline in oocyte quality. In this study, we generated a PCOS mice model by hypodermic injection of dehydroepiandrosterone, and metformin was used as a positive control drug to study the effect of pachymic acid (PA) on endocrine and oocyte quality in PCOS mice. Compared with the model group, the mice treated with PA showed the following changes (slower weight gain, improved abnormal metabolism; increased development potential of GV oocytes, reduced number of abnormal MII oocytes, and damaged embryos; lower expression of ovarian-related genes in ovarian tissue and pro-inflammatory cytokines in adipose tissue). All these aspects show similar effects on metformin. Most notably, PA is superior to metformin in improving inflammation of adipose tissue and mitochondrial abnormalities. It is suggested that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice. These findings suggest that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice., (© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Fine particulate matter (PM 2.5 ) has an adverse effect on reproductive function, in particular causing reduced male reproductive function, but relatively few studies have directly targeted its effects on female reproduction. To investigate the effects of PM 2.5 exposure on female reproduction, we exposed female mice to PM 2.5 by intratracheal instillation for 28 days, and evaluated apoptosis of ovarian granulosa cells and oocytes and the quality embryos after insemination. Our results showed increased numbers of apoptotic granulosa cells and oocytes after exposure to elevated concentrations of PM 2.5 , which had adverse effects on female fertility via compromising embryo development and quality. We conclude that PM 2.5 induced apoptosis of ovarian granulosa cells and oocytes leading to disrupted embryo development and female fertility in mice., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recently, graphene nanomaterials have attracted tremendous attention and have been utilized in various fields because of their excellent mechanical, thermal, chemical, optical properties, and good biocompatibility, especially in biomedical aspects. However, there is a concern that the unique characteristics of nanomaterials may have undesirable effects. Therefore, in this study, we sought to systematically investigate the effects of graphene quantum dots (GQDs) on the maturation of mouse oocytes and development of the offspring via in vitro and in vivo studies. In vitro, we found that the first polar body extrusion rate in the high dosage exposure groups (1.0-1.5 mg/ml) 2 decreased significantly and the failure of spindle migration and actin cap formation after GQDs exposure was observed. The underlying mechanisms might be associated with reactive oxygen species accumulation and DNA damage. Moreover, transmission electron microscope studies showed that GQDs may have been internalized into oocytes, tending to accumulate in the nucleus and severely affecting mitochondrial morphology, which included swollen and vacuolated mitochondria accompanied by cristae alteration with a lower amount of dense mitochondrial matrix. In vivo, when pregnant mice were exposed to GQDs at 8.5 days of gestation (GD, 8.5), we found that high dosage of GQD exposure (30 mg/kg) significantly affected mean fetal length; however, all the second generation of female mice grew up normal, attained sexual maturity, and gave birth to a healthy offspring after mating with a healthy male mouse. The results presented in this study are important for the future investigation of GQDs for the biomedical applications., (© 2019 Wiley Periodicals, Inc.)

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.

SKAP2 (Src kinase-associated phosphoprotein 2), a substrate of Src family kinases, has been suggested to be involved in actin-mediated cellular processes. However, little is known about its role in mouse oocyte maturation. In this study, we thus investigated the expression, localization, and functions of SKAP2 during mouse oocyte asymmetric division. SKAP2 protein expression was detected at all developmental stages in mouse oocytes. Immunofluorescent staining showed that SKAP2 was mainly distributed at the cortex of the oocytes during maturation. Treatment with cytochalasin B in oocytes confirmed that SKAP2 was co-localized with actin. Depletion of SKAP2 by injection with specific short interfering RNA caused failure of spindle migration, polar body extrusion, and cytokinesis defects. Meanwhile, the staining of actin filaments at the oocyte membrane and in the cytoplasm was significantly reduced after these treatments. SKAP2 depletion also disrupted actin cap and cortical granule-free domain formation, and arrested a large proportion of oocytes at the telophase stage. Moreover, Arp2/3 complex and WAVE2 expression was decreased after the depletion of SKAP2 activity. Our results indicate that SKAP2 regulates the Arp2/3 complex and is essential for actin-mediated asymmetric cytokinesis by interacting with WAVE2 in mouse oocytes.

KIF2A, a member of the kinesin-13 family, has been reported to play a role in spindle assembly in mitosis. However, its function in mammalian meiosis remains unknown. In this research, we examined the expression, localization and function of KIF2A during mouse oocyte meiosis. KIF2A was expressed in some key stages in mouse oocyte meiosis. Immunofluorescent staining showed that KIF2A distributed in the germinal vesicle at the germinal vesicle stage and as the spindle assembling after meiosis resumption, KIF2A gradually accumulated to the entire spindle. The treatment of oocytes with taxol and nocodazole demonstrated that KIF2A was co-localized with α-tubulin. Depletion of KIF2A by specific short interfering (si) RNA injection resulted in abnormal spindle assembly, failure of spindle migration, misaligned chromosomes and asymmetric cell division. Meanwhile, SKA1 expression level was decreased and the TACC3 localization was disrupted. Moreover, depletion of KIF2A disrupted the actin cap formation, arrested oocytes at metaphase I with spindle assembly checkpoint protein BubR1 activated and finally reduced the rate of the first polar body extrusion. Our data indicate that KIF2A regulates the spindle assembly, asymmetric cytokinesis and the metaphase I-anaphase I transition in mouse oocyte.

Methoxychlor (MXC) is used worldwide against insects and other pests. This organochlorine pesticide acts as a xenoestrogen, promotes oxidative stress, and is considered cytotoxic and genotoxic, causing abortions and stillbirths in females. Mechanistically related estrogens and oxidants affect oocyte meiosis, so we investigated the effects of MXC on mouse oocyte meiotic maturation. Our results showed that maturation rates of MXC-treated oocytes were lower than those of controls, which was due to abnormal spindle morphologies and DNA double-strand breaks, as confirmed by increased γ-H2AX foci. Our findings also suggest that MXC may affect oocyte quality by causing the accumulation of superoxide radicals and other reactive oxygen species, aberrant mitochondrial distribution, decreased mitochondrial membrane potential, and increased lipid peroxidation. Thus, exposure to MXC negatively affects oocyte meiotic maturation, primarily through impairments in cellular ROS metabolism. Mol. Reprod. Dev. 83: 768-779, 2016 © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Axin-1, a negative regulator of Wnt signaling, is a versatile scaffold protein involved in centrosome separation and spindle assembly in mitosis, but its function in mammalian oogenesis remains unknown. Here we examined the localization and function of Axin-1 during meiotic maturation in mouse oocytes. Immunofluorescence analysis showed that Axin-1 was localized around the spindle. Knockdown of the Axin1 gene by microinjection of specific short interfering (si)RNA into the oocyte cytoplasm resulted in severely defective spindles, misaligned chromosomes, failure of first polar body (PB1) extrusion, and impaired pronuclear formation. However, supplementing the culture medium with the Wnt pathway activator LiCl improved spindle morphology and pronuclear formation. Downregulation of Axin1 gene expression also impaired the spindle pole localization of γ-tubulin/Nek9 and resulted in retention of the spindle assembly checkpoint protein BubR1 at kinetochores after 8.5 h of culture. Our results suggest that Axin-1 is critical for spindle organization and cell cycle progression during meiotic maturation in mouse oocytes.

Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear. In this study, using a mouse gastric lavage model, we report that four weeks of atrazine exposure affects body growth, interferes with the estrous cycle, and increases the number of atretic follicles in mice. The expression levels of follicle development related factors StAR, BMP15, and AMH decreased. Metabolomic analysis revealed that atrazine activates an inflammatory response in ovarian tissue. Further studies confirmed that the expression levels of TNF-α, IL-6, and NF-κB increased in the ovaries of mice exposed to atrazine. Additionally, α-smooth muscle actin (α-SMA) accumulated in ovarian tissue, and transforming growth factor-β (TGF-β) signaling was activated, indicating the occurrence of tissue fibrosis. Moreover, mice exposed to atrazine produced fewer oocytes and exhibited reduced embryonic development. Furthermore, mice exposed to atrazine exhibited altered gut microbiota abundance and a disrupted colon barrier. Collectively, these findings suggest that atrazine exposure induces ovarian inflammation and fibrosis, disrupts ovarian homeostasis, and impairs follicle maturation, ultimately reducing oocyte quality. [Display omitted] • Atrazine exposure induces ovary inflammation and fibrosis. • Oocytes and embryo development would be interfered with atrazine exposure. • Loss of intestinal barrier integrity participates in atrazine induced ovary toxicity. [ABSTRACT FROM AUTHOR]