RESUMEN
Dehydroepiandrosterone (DHEA) is frequently integrated as an adjuvant in over a quarter of controlled ovarian hyperstimulation (COH) protocols, despite the ongoing debate regarding its impact. This study aimed to evaluate the efficacy and mechanism of action of DHEA on ovarian follicular development and ovarian response in rats with varying ovarian reserves. The study involved 75 rats categorized into 15 distinct groups. The ovarian tissues of rats in both the normal ovarian reserve group and the premature ovarian insufficiency (POI) group, induced by 4-vinylcyclohexene diepoxide (VCD) injection, were subjected to histomorphological and biochemical analyses following the administration of DHEA, either alone or in combination with COH. Follicle counting was performed on histological sections obtained from various tissues. Serum concentrations of anti-Müllerian hormone (AMH) and the quantification of specific proteins in ovarian tissue, including phosphatase and tensin homolog of chromosome 10 (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT), cyclooxygenase 2 (COX-2), caspase-3, as well as assessments of total antioxidant status and total oxidant status, were conducted employing the ELISA method. The impact of DHEA exhibited variability based on ovarian reserve. In the POI model, DHEA augmented follicular development and ovarian response to the COH protocol by upregulating the PTEN/PI3K/AKT signaling pathway, mitigating apoptosis, inflammation, and oxidative stress, contrary to its effects in the normal ovarian reserve group. In conclusion, it has been determined that DHEA may exert beneficial effects on ovarian stimulation response by enhancing the initiation of primordial follicles and supporting antral follicle populations.
Asunto(s)
Ciclohexenos , Deshidroepiandrosterona , Fosfohidrolasa PTEN , Fosfatidilinositol 3-Quinasas , Insuficiencia Ovárica Primaria , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Compuestos de Vinilo , Animales , Femenino , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/metabolismo , Fosfohidrolasa PTEN/metabolismo , Ciclohexenos/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Deshidroepiandrosterona/farmacología , Deshidroepiandrosterona/administración & dosificación , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Ovario/efectos de los fármacos , Ovario/metabolismo , Reserva Ovárica/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/metabolismoRESUMEN
BACKGROUND: Parenteral nutrition (PN) has been widely used in preterm infants. The lipid solutions used for PN, however, are associated with oxidative stress and morbidity. The aim of this study was to compare the effectiveness of a new-generation lipid emulsion (SMOFLipid) and olive-oil based lipid emulsion for prevention of PN-associated oxidative damage. METHODS: Preterm infants < 32 weeks of gestational age were included in this prospective randomized study. All infants were randomized to SMOFlipid or olive-oil based lipid emulsion (ClinOleic). Lipid peroxidation products were evaluated in all infants. In addition, total antioxidant capacity (TAC), and both pro- and anti-inflammatory cytokines were studied at days 0, 7 and 14. RESULTS: A total of 89 infants (SMOFlipid, n = 42; ClinOleic, n = 47) were enrolled. TAC was higher in the SMOFlipid group compared with the ClinOleic group at all time points, and the difference on day 7 was statistically significant. Although the anti-inflammatory cytokine interleukin-10 was higher in the SMOFlipid group, this difference was not significant. Bronchopulmonary dysplasia (BPD) was lower in the SMOFlipid group (14.1%) than in the ClinOleic group (31.2%), but this finding was non-significant p > 0.05. The rate of severe BPD was significantly lower in the SMOFlipid group. CONCLUSION: To our best of knowledge, this is the first study to suggest that SMOFlipid might decrease oxidative damage and oxidative-stress-associated morbidity compared with olive oil-based emulsion in preterm infants.