Background: Follicular fluid (FF) contains compounds that can modulate NADP(+)-dependent oxidation of cortisol by type 1 11beta-hydroxysteroid dehydrogenase (11betaHSD). The objective of this study was to investigate the relationships between levels of the ovarian modulators of type 1 11betaHSD, intra-follicular cortisol:cortisone ratios and the clinical outcome of IVF cycles.
Methods: A single random sample of FF was aspirated from each of 132 patients undergoing gonadotrophin-stimulated IVF. Components of FF, resolved using C18 column chromatography, were evaluated for effects on NADP(+)-dependent cortisol oxidation in rat kidney homogenates. Intra- follicular steroid concentrations were measured by radioimmunoassays. Clinical pregnancies were confirmed by ultrasonography at 6 weeks post-embryo transfer.
Results: Levels of the hydrophilic ovarian 11betaHSD stimuli were significantly lower (P<0.0001) and levels of the hydrophobic ovarian 11betaHSD inhibitors were significantly higher (P<0.002) in conception versus non-conception cycles. Intra-follicular cortisol:cortisone ratios increased with the degree of inhibition of 11betaHSD by the hydrophobic FF fractions. FF obtained from conception cycles had significantly higher cortisol:cortisone ratios than samples from non-conception cycles (12.9+/-0.3 versus 8.5+/-0.2, respectively; P<0.0001).
Conclusions: Conception by IVF is associated with elevated intra-follicular cortisol:cortisone ratios, which reflect low levels of ovarian stimuli and/or high levels of ovarian inhibitors of type 1 11betaHSD.
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http://dx.doi.org/10.1093/humrep/deg322 | DOI Listing |
Reprod Fertil Dev
January 2025
CNRS, INRAE, Université de Tours, PRC, Nouzilly, France.
Female infertility, which affects 10-20% of couples worldwide, is a growing health concern in developing countries. It can be caused by multiple factors, including reproductive disorders, hormonal dysfunctions, congenital malformations and infections. In vitro and in vivo studies have shown that plant extracts regulate gonadotropin-releasing hormone, kisspeptin, and gonadotropin expression and/or secretion at the hypothalamic-pituitary level and modulate somatic and germ cells, such as steroidogenesis, proliferation, apoptosis, and oxidative stress at the ovarian level.
View Article and Find Full Text PDFMol Cancer Ther
January 2025
University of Michigan-Ann Arbor, Ann Arbor, MI, United States.
Up to 90% of high-grade serous ovarian cancer (HGSC) patients will develop resistance to platinum-based chemotherapy, posing substantial therapeutic challenges due to a lack of universally druggable targets. Leveraging BenevolentAI's AI-driven approach to target discovery, we screened potential AI-predicted therapeutic targets mapped to unapproved tool compounds in patient-derived 3D models. This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
February 2025
Department of Gynecology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
Lycopene (LYC) is an extremely powerful antioxidant with the potential to treat a range of diseases and to inhibit ferroptosis. This research aims to elucidate how LYC impacts polycystic ovarian syndrome (PCOS) and the action mechanisms. A PCOS rat model was constructed by injecting DHEA.
View Article and Find Full Text PDFCancer Cell Int
January 2025
Department of Gynecology, Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China.
Background: Ovarian cancer (OC) remains a lethal gynecological malignancy with an alarming mortality rate, primarily attributed to delayed diagnosis and a lack of effective treatment modalities. Accumulated evidence highlights the pivotal role of reprogrammed lipid metabolism in fueling OC progression, however, the intricate underlying molecular mechanisms are not fully elucidated.
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J Ovarian Res
January 2025
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, #128 Shenyang Road, Shanghai, 200090, People's Republic of China.
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