RESUMEN
The initial formation of the follicular antrum (iFFA) serves as a dividing line between gonadotropin-independent and gonadotropin-dependent folliculogenesis, enabling the follicle to sensitively respond to gonadotropins for its further development. However, the mechanism underlying iFFA remains elusive. Herein, we reported that iFFA is characterized by enhanced fluid absorption, energy consumption, secretion, and proliferation and shares a regulatory mechanism with blastula cavity formation. By use of bioinformatics analysis, follicular culture, RNA interference, and other techniques, we further demonstrated that the tight junction, ion pumps, and aquaporins are essential for follicular fluid accumulation during iFFA, as a deficiency of any one of these negatively impacts fluid accumulation and antrum formation. The intraovarian mammalian target of rapamycin-C-type natriuretic peptide pathway, activated by follicle-stimulating hormone, initiated iFFA by activating tight junction, ion pumps, and aquaporins. Building on this, we promoted iFFA by transiently activating mammalian target of rapamycin in cultured follicles and significantly increased oocyte yield. These findings represent a significant advancement in iFFA research, further enhancing our understanding of folliculogenesis in mammals.
Asunto(s)
Acuaporinas , Uniones Estrechas , Animales , Femenino , Acuaporinas/genética , Hormona Folículo Estimulante , Gonadotropinas , Bombas Iónicas , Mamíferos , Serina-Treonina Quinasas TOR/genética , Ratones , Péptido Natriurético Tipo-C/metabolismoRESUMEN
Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.
RESUMEN
Hierarchical functional structure plays a crucial role in brain function. We aimed to investigate how aging affects hierarchical functional structure and to evaluate the relationship between such effects and molecular, microvascular, and cognitive features. We used resting-state functional magnetic resonance imaging (fMRI) data from 95 older adults (66.94 ± 7.23 years) and 44 younger adults (21.8 ± 2.53 years) and employed an innovative graph-theory-based analysis (stepwise functional connectivity (SFC)) to reveal the effects of aging on hierarchical functional structure in the brain. In the older group, an SFC pattern converged on the primary sensory-motor network (PSN) rather than the default mode network (DMN). Moreover, SFC decreased in the DMN and increased in the PSN at longer link-steps in aging, indicating a reconfiguration of brain hub systems during aging. Subsequent correlation analyses were performed between SFC values and molecular, microvascular features, and behavioral performance. Altered SFC patterns were associated with dopamine and serotonin, suggesting that altered hierarchical functional structure in aging is linked to the molecular fundament with dopamine and serotonin. Furthermore, increased SFC in the PSN, decreased SFC in the DMN, and accelerated convergence rate were all linked to poorer microvascular features and lower executive function. Finally, a mediation analysis among SFC features, microvascular features, and behavioral performance indicated that the microvascular state may influence executive function through SFC features, highlighting the interactive effects of SFC features and microvascular state on cognition.
RESUMEN
Introduction: High-intensity interval training (HIIT) is an emerging lifestyle intervention strategy for controlling obesity. HIIT consisted of brief all-out supramaximal sprint intervals was termed as sprint interval training (SIT). This study was designed to examine the time-efficient characteristics of SIT in reducing abdominal visceral fat. Methods: A randomized controlled trial was conducted to compare the specific adaptations of SIT (80 × 6 s all-out cycle sprints interspersed with 9 s passive recovery) with those resulting from a HIIT regimen with training volume relatively higher (repeated 4 min bouts of cycling at 90% VË O2max alternated with 3 min rest, until the work of 400KJ was achieved), and with those of nonexercising control counterparts (CON). Forty-six obese young women (body fat percentage ≥30) received either SIT (n = 16), HIIT (n = 16), or no training (n = 14), 3-4 sessions per week, for 12 weeks. The abdominal visceral fat area (AVFA) and abdominal subcutaneous fat area (ASFA) of the participants were measured through computed tomography scans pre-intervention and post-intervention. Total fat mass and the fat mass of the android, gynoid, and trunk regions were assessed through dual-energy X-ray absorptiometry. Results: Following the intervention, abdominal visceral and subcutaneous fat were reduced markedly (p < 0.05). The reduction in AVFA (-6.31, -9.7 cm2) was not different between SIT and HIIT (p > 0.05), while the reduction in ASFA (-17.4, -40.7 cm2) in SIT was less than that in HIIT (p < 0.05). Less reduction in the fat mass of the trunk (-1.2, -2.0 kg) region was also found in SIT, while the reductions in fat percentage (-1.9%, -2.0%), total fat mass (-2.0, -2.8 kg), and fat mass of the android (-0.2, -0.2 kg), and gynoid (-0.4, -0.3 kg) regions did not differ between the two regimes (p > 0.05). In contrast, the increase in VË O2max was significant greater following the SIT than HIIT (p < 0.01). No variable changed in CON. Conclusion: Such findings suggest that the lower training load and exercise time commitments of the SIT regime could optimize the time-efficiency advantage of the traditional HIIT, facilitating the abdominal visceral fat reduction in obese young women.