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Abstract The oocyte cumulus complex is mainly composed of an oocyte, the perivitelline space, zona pellucida and numerous granulosa cells. The cumulus granulosa cells (cGCs) provide a particularly important microenvironment for oocyte development, regulating its growth, maturation and meiosis. In this study, we studied the internal structures and cell-to-cell connections of mouse cGCs using focused ion beam scanning electron microscopy (FIB-SEM). We reconstructed three-dimensional models to display characteristic connections between the oocyte and cGCs, and to illustrate various main organelles in cGCs together with their interaction relationship. A special form of cilium identified in granulosa cell was never reported in previous literature.

Photoaggravated dermatoses (PD) are diseases that occur without ultraviolet (UV) radiation but are sometimes or frequently exacerbated by UV radiation. The clinical manifestations of PD are varied, some patients may present with pruritic nodular lesions at the site of light exposure, which possibly through a light-induced type 2 inflammatory response. Some cases may be difficult to treat, safe and effective treatment methods are constantly being explored. Here, we reported five patients with moderate to severe PD with skin nodules as main manifestations successfully treated with dupilumab, who were previously resistant to conventional treatment. After the 16-week treatment period, dupilumab showed good efficacy and safety in PD mainly characterized by nodules.

IntroductionThin endometrium leads to an impaired implantation rate. The aim of the study is to compare the clinical outcomes of tamoxifen (TAM) and hormone replacement therapy (HRT) used in patients with thin endometrium (0.05). The early miscarriage rate was significantly lower in the TAM group compared with the HRT group (5.9% Vs 26.8%, adjusted OR 0.10, p

Summary: γδ T cells make key contributions to tissue physiology and immunosurveillance through two main functionally distinct subsets, γδ T1 and γδ T17. m6A methylation plays critical roles in controlling numerous aspects of mRNA metabolism that govern mRNA turnover, gene expression, and cellular functional specialization; however, its role in γδ T cells remains less well understood. Here, we find that m6A methylation controls the functional specification of γδ T17 vs. γδ T1 cells. Mechanistically, m6A methylation prevents the formation of endogenous double-stranded RNAs and promotes the degradation of Stat1 transcripts, which converge to prevent over-activation of STAT1 signaling and ensuing inhibition of γδ T17. Deleting Mettl3, the key enzyme in the m6A methyltransferases complex, in γδ T cells reduces interleukin-17 (IL-17) production and ameliorates γδ T17-mediated psoriasis. In summary, our work shows that METTL3-mediated m6A methylation orchestrates mRNA stability and double-stranded RNA (dsRNA) contents to equilibrate γδ T1 and γδ T17 cells.

Endometriosis is defined as a disorder in which the glands and stroma of the endometrium grow and shed periodically outside the uterine cavity. Highly prevalent in women of reproductive age, the most common clinical manifestations are chronic pelvic pain and infertility. The pathogenesis of endometriosis may be multifactorial, including factors of anatomy, immunity, inflammation, hormones (estrogen), oxidative stress, genetics, epigenetics, and environment. There are generally three types of endometriotic disease, namely peritoneal, ovarian, and deep infiltration. For the same patient, there may be a single or multiple types concurrently. The different manifestations of these types suggests that they each have their own etiology. Numerous studies have shown that the evasion of endometrial cells from peritoneal immune surveillance helps establish and maintain peritoneal endometriosis, but the specific mechanism is not well understood. Likewise, the molecular mechanisms of endometriosis-related infertility have not been clearly elucidated. This review attempts to identify the role of peritoneal immunity in peritoneal endometriosis and related infertility, especially in the aspects of molecular mechanisms.

Abstract Endometriosis is one of the most common disorders that causes infertility in women. Iron is overloaded in endometriosis peritoneal fluid (PF), with harmful effects on early embryo development. However, the mechanism by which endometriosis peritoneal fluid affects embryonic development remains unclear. Hence, this study investigated the effect of iron overload on mouse embryos and elucidated the molecular mechanism. Iron overload in endometriosis PF disrupted blastocyst formation, decreased GPX4 expression and induced lipid peroxidation, suggesting that iron overload causes embryotoxicity and induces ferroptosis. Moreover, mitochondrial damage occurs in iron overload-treated embryos, presenting as decreased ATP levels, increased ROS levels and MMP hyperpolarization. The cytotoxicity of iron overload is attenuated by the ferroptosis inhibitor Fer-1. Furthermore, Smart-seq analysis revealed that HMOX1 is upregulated in embryo ferroptosis and that HMOX1 suppresses ferroptosis by maintaining mitochondrial function. This study provides new insight into the mechanism of endometriosis infertility and a potential target for future endometriosis infertility treatment efforts.

Objective: To establish mouse endometrial injury model by curettage or coagulation. Methods: Female ICR mice were randomly allocated into 2 groups: in curettage group, a blunt 20G needle was inserted in one uterine horn with 0.05 megapascals negative pressure; in coagulation group, one uterine horn was coagulated using a monopolar electric needle with 0.5 watts power. In both groups the contra-lateral uterine horn was used as control. The morphological changes and thickness of endometrium were evaluated 1 week after operation. The endometrial samples were taken on d4 of pregnancy, and the expressions of endometrial receptivity-related cytokines were examined. The number of implanted embryos on each side of uterus was calculated on d10 of pregnancy. Results: There was no difference in operation time between 2 groups. In both groups, the endometrial glands and stroma were significantly reduced, and the endometrial thickness was also significantly decreased on injury side compared to contra-lateral horn. However, local injury was more severe in coagulation group, uterine obliteration and hydrops were developed in 2 mice of coagulation group, and none in curettage group. The expressions of leukemia inhibitory factor (LIF) and oncostatin M (OSM) were significantly reduced on injured side in both groups compared to opposite side; however, the expression of LIF and OSM in curettage group was higher than that in coagulation group. The numbers of implanted embryos were decreased in both groups on injured side compared to opposite side, and fetal death was only observed in coagulation group. Conclusion: Both curettage and coagulation can make injury on mouse endometrium, impair endometrial receptivity and reduce fertility. Curettage can cause moderate injury, and coagulation may lead to more severe injury.