Ovarian tissue contains large pools of immature oocytes enclosed in primordial follicles, making it an attractive target for fertility preservation in female cancer patients, livestock and wild species. Compared to cryopreservation, desiccation and long-term storage of samples at supra-zero temperatures (using strategies inspired from small organisms to resist extreme environments) would be more cost-effective and convenient. The objective of the study was to characterize the influence of microwave-assisted dehydration on structural and functional properties of living ovarian tissues. While this method allows preservation of single cells (cat oocytes and sperm cells so far) using trehalose as the xeroprotectant, it has not been developed for multicellular tissues yet. Ovarian cortex biopsies were reversibly permeabilized, exposed to various concentrations of trehalose, and dried for different times using a commercial microwave under thermal control. Effective dehydration of samples along with proper trehalose retention were reached within 30 min of microwave drying. Importantly, the process did not affect morphology and DNA integrity of follicles or stromal cells. Moreover, transcriptional activity and survival of follicles were partially maintained following 10 min of drying, which already was compatible with storage at non-cryogenic temperatures. Present data provide critical foundation to develop dry-preservation techniques for long-term storage of living multicellular tissues.
Preeclampsia (PE) is a hypertensive disorder of pregnancy occurring in approximately 10% of women worldwide. While it is life threatening to both the mother and baby, the only effective treatment is delivery of the placenta and fetus, which is often preterm. Maternal obesity is a risk factor for PE, and the effects of both on offspring are long standing with increased incidence of cardiometabolic disease in adulthood. Obese BPH/5 mice spontaneously exhibit excessive gestational weight gain and late-gestational hypertension, similar to women with PE, along with fetal growth restriction and accelerated compensatory growth in female offspring. We hypothesized that BPH/5 male offspring will demonstrate cardiovascular and metabolic phenotypes similar to BPH/5 females. As previously described, BPH/5 females born to ad libitum-fed dams are overweight with hyperphagia and increased subcutaneous, peri-renal, and peri-gonadal white adipose tissue (WAT) and cardiomegaly compared to age-matched adult female controls. In this study, BPH/5 adult male mice have similar body weights and food intake compared to age-matched control mice but have increased inflammatory subcutaneous and peri-renal WAT and signs of cardiovascular disease: left ventricular hypertrophy and hypertension. Therefore, adult male BPH/5 do not completely phenocopy the cardiometabolic profile of female BPH/5 mice. Future investigations are necessary to understand the differences observed in BPH/5 male and female mice as they age. In conclusion, the impact of fetal programming due to PE has a transgenerational effect on both male and female offspring in the BPH/5 mouse model. The maternal obesogenic environment may play a role in PE pregnancy outcomes, including offspring health as they age.
Preeclampsia (PE) is a hypertensive disorder that impacts 2–8% of pregnant women worldwide. It is characterized by new onset hypertension during the second half of gestation and is a leading cause of maternal and fetal morbidity/mortality. Maternal obesity increases the risk of PE and is a key predictor of childhood obesity and potentially offspring cardiometabolic complications in a sex‐dependent manner. The influence of the maternal obesogenic environment, with superimposed PE, on offspring development into adulthood is unknown. Obese BPH/5 mice spontaneously exhibit late‐gestational hypertension, fetal demise and growth restriction, and excessive gestational weight gain. BPH/5 females have improved pregnancy outcomes when maternal weight loss via pair‐feeding is imposed beginning at conception. We hypothesized that phenotypic differences between female and male BPH/5 offspring can be influenced by pair feeding BPH/5 dams during pregnancy. BPH/5 pair‐fed dams have improved litter sizes and increased fetal body weights. BPH/5 offspring born to ad libitum dams have similar sex ratios, body weights, and fecal microbiome as well as increased blood pressure that is reduced in the dam pair‐fed offspring. Both BPH/5 male and female offspring born to pair‐fed dams have a reduction in adiposity and an altered gut microbiome, while only female offspring born to pair‐fed dams have decreased circulating leptin and white adipose tissue inflammatory cytokines. These sexually dimorphic results suggest that reduction in the maternal obesogenic environment in early pregnancy may play a greater role in female BPH/5 sex‐dependent cardiometabolic outcomes than males. Reprograming females may mitigate the transgenerational progression of cardiometabolic disease.
Obesity impacts 1/3 of US adults. Maternal obesity significantly increases risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 have increased visceral white adipose tissue (WAT) and are leptin resistant. We hypothesize that attenuation of maternal obesity and reduction of reproductive WAT in pregnant BPH/5 female mice will improve decidualization, placental development, and attenuate FGR. To test this hypothesis, pregnant C57 and BPH/5 female mice fed ad libitum (lib) and pair-fed (PF) BPH/5 female mice, beginning at day of copulatory plug detection, e0.5 (n=5/group), were utilized. Pair-feeding BPH/5 females the equivalent daily food intake of lean control ad lib fed C57 females reduced maternal WAT and circulating leptin in this model by e7.5 as well as reduced pro-inflammatory cytokines, Ptgs2 and IL-6, mRNA in the decidua. Therefore, we tested whether hypoxia-related genes, hypoxia inducible factor (Hif) 1α, heme oxygenase-1 (Ho-1), and stem cell factor (Scf), would be altered in the decidua of PF BPH/5 at e7.5. Using real time PCR, we found that e7.5 implantation sites from ad lib fed BPH/5 had a 1.5 to 2-fold increase in Hif1α, Ho-1, Scf, and VEGF mRNA (p<0.05) compared to C57 that was significantly reduced by PF. Furthermore, real time PCR for leptin (lep) mRNA showed a 6-fold increase in e7.5 implantation sites from ad lib fed BPH/5 versus C57 and lep along with lep receptor mRNA was reduced in PF BPH/5 (p<0.05). Therefore, PF BPH/5 pregnant mice have attenuated obesity and leptin in WAT, circulation, and e7.5 implantation sites that is associated with a reduction in markers of hypoxia at the maternal-fetal interface. Finally, BPH/5 PF litter sizes are significantly higher than ad lib fed, 6 vs 3.5, respectively (n=5-8; p<0.05) and symmetrical FGR is attenuated. In conclusion, maternal weight loss in BPH/5 beginning at conception may improve placental development by mitigating hypoxia at the maternal-fetal interface in this model. Future investigations are needed to determine this effect on the maternal hypertensive syndrome and offspring outcomes long-term.
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