| 1. |
- Adhikari, Deepak, et al.
(författare)
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The Safe Use of a PTEN Inhibitor for the Activation of Dormant Mouse Primordial Follicles and Generation of Fertilizable Eggs
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primordial ovarian follicles, which are often present in the ovaries of premature ovarian failure (POF) patients or are cryopreserved from the ovaries of young cancer patients who are undergoing gonadotoxic anticancer therapies, cannot be used to generate mature oocytes for in vitro fertilization (IVF). There has been very little success in triggering growth of primordial follicles to obtain fertilizable oocytes due to the poor understanding of the biology of primordial follicle activation. Methodology/Principal Findings: We have recently reported that PTEN (phosphatase and tensin homolog deleted on chromosome ten) prevents primordial follicle activation in mice, and deletion of Pten from the oocytes of primordial follicles leads to follicular activation. Consequently, the PTEN inhibitor has been successfully used in vitro to activate primordial follicles in both mouse and human ovaries. These results suggest that PTEN inhibitors could be used in ovarian culture medium to trigger the activation of primordial follicle. To study the safety and efficacy of the use of such inhibitors, we activated primordial follicles from neonatal mouse ovaries by transient treatment with a PTEN inhibitor bpV(HOpic). These ovaries were then transplanted under the kidney capsules of recipient mice to generate mature oocytes. The mature oocytes were fertilized in vitro and progeny mice were obtained after embryo transfer. Results and Conclusions: Long-term monitoring up to the second generation of progeny mice showed that the mice were reproductively active and were free from any overt signs or symptoms of chronic illnesses. Our results indicate that the use of PTEN inhibitors could be a safe and effective way of generating mature human oocytes for use in novel IVF techniques.
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| 2. |
- Risal, Sanjiv, et al.
(författare)
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Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome
- 2019
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Ingår i: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 25:12, s. 1894-1904
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Tidskriftsartikel (refereegranskat)abstract
- How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.
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| 3. |
- Wang, Aozhe, et al.
(författare)
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Targeted lipidomics and inflammation response to six weeks of sprint interval training in male adolescents
- 2023
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- Lipids play an important role in coordinating and regulating metabolic and inflammatoryprocesses. Sprint interval training (SIT) is widely used to improve sports performance and healthoutcomes, but the current understanding of SIT-induced lipid metabolism and the correspondingsystemic inflammatory status modification remains controversial and limited, especially in maleadolescents. To answer these questions, twelve untrained male adolescents were recruited andunderwent 6 weeks of SIT. The pre- and post-training testing included analyses of peak oxygenconsumption (VO2peak), biometric data (weight and body composition), serum biochemical pa-rameters (fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-densitylipoprotein cholesterol, triacylglycerol, testosterone, and cortisol), inflammatory markers, and tar-geted lipidomics. After the 6-week SIT, the serum C-reactive protein (CRP), interleukin (IL)-1β, IL-2,IL-4, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β significantlydecreased (p < 0.05), whereas IL-6 and IL-10/TNF-α significantly increased (p < 0.05). In addition,the targeted lipidomics revealed changes in 296 lipids, of which 33 changed significantly (p < 0.05,fold change > 1.2 or <1/1.2). The correlation analysis revealed that the changes in the inflammatorymarkers were closely correlated with the changes in some of the lipids, such as LPC, HexCer, andFFA. In conclusion, the 6-week SIT induced significant changes in the inflammatory markers andcirculating lipid composition, offering health benefits to the population.
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