Human semen cryopreservation in the clinical management of male infertility is complicated by cryodamage to spermatozoa. We aimed to clarify the full pattern of cryodamage and evaluate the protective effects of ascorbate and catalase on cryopreserved spermatozoa. Semen samples were collected from 30 fertile males. Each sample was divided into 6 groups: fresh semen, cryopreserved semen without treatment, and samples cryopreserved with ascorbate (300 or 600 mM) or catalase (200 or 400 IU/mL). Spermatozoa were examined for their viability, motility, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), apoptosis (positive for annexin V and negative for propidium iodide [ie, Ann, and DNA damage (Olive tail moment [OTM]) in the presence or absence of ascorbate or catalase during cryopreservation. In comparison with the fresh spermatozoa, there was a significant decrease in the viability, motility, and MMP but increase in Ann + /PI 2 and OTM in the cryopreserved spermatozoa (P , .01 and P , .05, respectively). Concurrently, ROS levels in the postthaw spermatozoa also increased significantly, and this elevation was well correlated with the quality variations of postthaw spermatozoa (P , .01 for all). Ascorbate (300 mM) and catalase (200 and 400 IU/mL) reduced the ROS levels in postthaw spermatozoa significantly, compared with those in the control (P , .05). Furthermore, these antioxidants also prevented those characteristics from being adversely affected (P , .05). This study demonstrated that cryopreservation results in cryodamage to human spermatozoa, possibly through the mechanism of ROS. Appropriate ascorbate or catalase supplementation of cryoprotective medium restrains ROS levels and the resultant cryodamage.
Electronic waste (e-waste) is the fastest growing solid waste stream worldwide and mostly ends up in developing countries where residents use primitive methods for recycling. The most infamous e-waste recycling town, Guiyu in Southeast China, has been recycling since the mid-1990s. E-waste contains several harmful chemicals, including lead (Pb), cadmium (Cd), chromium (Cr), and manganese (Mn). In 2011-12, the e-waste Recycling Exposures and Community Health (e-REACH) Study enrolled 634 pregnant women living in Guiyu and Haojiang, a control site, both in Shantou, China. The women completed a questionnaire and gave maternal blood, cord blood, and maternal urine, which were analyzed for Pb, Cd, Cr, and Mn. Maternal blood Pb, Cd, and Cr concentrations were significantly higher in Guiyu compared to Haojiang. In Guiyu, the geometric mean of Pb concentration in maternal blood was 6.66 µg/dL (range: 1.87-27.09 µg/dL) and was 1.74-fold greater than in Haojiang (95% CI: 1.60, 1.89). In cord blood, Pb concentration was 1.53-fold higher in Guiyu (95% CI: 1.38, 1.68). In maternal urine, Cd (ratio: 2.15, 95% CI: 1.72, 2.69) and Mn (ratio: 2.60, 95% CI: 2.04, 3.31) concentrations were significantly higher in Guiyu in comparison to Haojiang. In conclusion, pregnant women in Guiyu were at risk for increased exposure to heavy metals.
In the absence of overt thyroid dysfunction, THs are positively associated with AGD in male newborns. TH effects on body size and head circumference may be modified by maternal secondhand smoke exposure.
The survival of ovary granulosa cells (GC) is critical in the initiation and progression of polycystic ovary syndrome (PCOS) in females. Here, we found that the PCOS process is accompanied by massive GC pyroptosis resulting from Caspase-1 inflammasome activation. Administration of plumbagin, an effective compound isolated from plant medicine, can prevent the pyroptosis of GC and the onset of PCOS. Mechanistic study indicates the over-activation of the inflammasome in GC is due to the upregulation of WTAP, a key regulator of the RNA N6-methylase complex. WTAP mediates the mRNA N6-methylation of NLRP3 inflammasome component ASC and enhances ASC RNA stability, which results in the overactivation of the inflammasome in GCs from the PCOS model. Plumbagin treatment suppresses the WTAP-mediated N6-methylation of ASC mRNA and reduces the pyroptosis of GCs. This study supports the profound potential of plumbagin in PCOS treatment. Graphical Abstract
Although using letrozole (LE) during in vitro fertilisation and intracytoplasmic sperm injection (IVF/ICSI) has many advantages, it remains unclear whether LE induces an increase in progestogen during the late follicular phase. The objective of this study was to investigate whether progesterone levels increased under antagonist protocols supplemented with LE on the trigger day using a retrospective cohort study. The study included 1,133 women who underwent IVF/ICSI cycles from January 2018 to June 2020. After propensity score matching (PSM) for baseline characteristics, 266 patients with gonadotropin-releasing hormone-antagonist (GnRH-ant) were matched to 266 patients with letrozole + GnRH-ant (LE GnRH-ant) (PSM 1 cohort), and 283 patients with gonadotropin-releasing hormone-agonist (GnRH-a) were matched to 283 patients with LE GnRH-ant (PSM 2 cohort). In the PSM 1 cohort, patients in the LE GnRH-a group presented higher progesterone levels (1.22 ± 0.95 ng/mL vs 0.86 ± 0.60 ng/mL, P < 0.001), with a higher proportion of patients with progesterone level > 1.5 ng/mL (24.81% vs 7.52%, P < 0.001). In PSM 2 cohort, patients in the LE GnRH-a group presented higher progesterone levels on trigger day (1.23 ± 0.91 ng/mL vs 0.98 ± 0.61 ng/mL, P < 0.001), with a higher proportion of patients with progesterone level > 1.5 ng/mL (25.45% vs 12.70%, P < 0.001). In the PSM 1 cohort, progesterone levels on the trigger day increased by 0.05 ng/mL, with an increase in every retrieved oocyte in the LE GnRH-ant group (β 0.05 ng/mL [95% CI 0.04, 0.06], P < 0.001), whereas an increase of 0.02 ng/mL was observed in the GnRH-ant group (β 0.02 ng/mL [95% CI 0.01, 0.03], P < 0.001), with P for interaction being 0.0018. In the PSM 2 cohort, progesterone levels on the trigger day increased by 0.05 ng/mL with an increase in every retrieved oocyte in the LE GnRH-ant group (β 0.05 ng/mL [95% CI 0.04, 0.06], P < 0.001), whereas an increase of 0.02 ng/mL was observed in the GnRH-a group (β 0.02 ng/mL [95% CI 0.01, 0.03], P < 0.001), with P for interaction being 0.0002. LE supplementation on the antagonist protocols may increase progesterone levels in the late follicular stage.
In vitro fertilization and embryo transfer is one type of assisted reproductive technology, although the technology is now more mature. Many factors, however, will have an impact on oocyte fertilization, embryo growth, pregnancy outcome, and child safety due to the journey from clinical to the laboratory. The influence of degranulated cells early in fertilization on frozen embryo transfer (FET) results is investigated in this study. This article analyzes 255 patients who underwent in vitro fertilization (IVF) and FET transplantation at the author’s central unit from January 1, 2015, to June 30, 2021. Among them, IVF-assisted conception is the early degranulation of homologous oocyte fertilization. Correlation analysis is performed by observing the embryonic outcome of the early degranulation group and the overnight fertilization group and the clinical outcome after FET. Through data mining analysis, the results show that the polyfertilization rate and 0PN rate for the early degranulation group are significantly higher than the overnight fertilization group (9.87% vs. 8.24% and 3.14% vs. 1.69%). In terms of normal fertilization rate, there is no significant difference between D3 high-quality embryo rate and D5 high-quality blastocyst rate (64.07% vs. 65.15%, 27.5% vs. 26.5%, and 15.97% vs. 17.35%). There is no significant difference in the complete recovery rate of embryos after thawing (93.24% vs. 93.46%), and the implantation rate, clinical pregnancy rate, abortion rate, and live birth rate are not significantly different between the two groups after FET. The offspring outcomes of singletons do not differ significantly between the two groups; however, twins born early degranulate have much greater rates of ultralow birth weight and ultrapreterm children than twins born overnight fertilization (14.29% vs. 0). Therefore, it can be concluded that degranulation of cells early in fertilization is a desirable method to prevent fertilization disorders. However, under the premise of ensuring that no fertilization disorder occurs, it is not appropriate to degranulate all the oocytes of the patient at the early stage of fertilization.
The expression of tumor stem cell markers musashi1 (msi1) and numb in brain metastases were detected to explore their roles in the development of brain metastases. A total of 51 cases of brain metastasis, 29 cases of primary tumor and 15 cases of normal brain tissue were selected. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were used to detect msi1 and numb expression at the protein and mRNA levels. Correlation between msi1 and numb in brain metastases were evaluated. Immunohistochemistry and RT-PCR showed that no significant difference in the expression of msi1 and numb between brain metastases and primary tumors was observed ( P > .05); the expression of msi1 and numb in brain metastases was significantly higher than that in normal brain tissues ( P < .05); and the expression of msi1 and numb in primary tumors was significantly higher than that in normal brain tissues ( P < .05). In general, the expression of msi1 gene was negatively correlated with the expression of numb at mRNA level by Pearson correlation analysis ( r = −0.345, P < .05). Additionally, the expression of msi1 and numb in brain metastases was not related to gender, age, and tissue origin ( P > .05). Msi1 is highly expressed in brain metastases and primary tumors, while numb is lowly expressed in brain metastases and primary tumors; msi1 and numb are negatively correlated in brain metastases, suggesting that msi1 and numb may have regulatory mechanisms in the development of brain metastases.
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