No abstract

The steroidogenic acute regulatory protein (StAR) governs the rate-limiting step in steroidogenesis, and its expression varies depending on the needs of the specific tissue. Tight control of steroid production is essential for multiple processes involved in reproduction, including follicular development, ovulation, and endometrial synchronization. Recently, there has been a growing interest in the role of noncoding RNAs in the regulation of reproduction. Here we demonstrate that StAR is a novel target of the microRNA let-7, which itself is regulated by the long noncoding RNA (lncRNA) H19. Using human and murine cell lines, we show that overexpression of H19 stimulates StAR expression by antagonizing let-7, which inhibits StAR at the post-transcriptional level. Our results uncover a novel mechanism underlying the regulation of StAR expression and represent the first example of lncRNA-mediated control of the rate-limiting step of steroidogenesis. This work thus adds to the body of literature describing the multiple roles in oncogenesis, cellular growth, glucose metabolism, and now regulation of steroidogenesis, of this complex lncRNA.

No abstract

In reproductive age women, the pool of primordial follicles is continuously depleted through the process of cyclic recruitment. AMH both inhibits the initial recruitment of primordial follicles into the growing pool and modulates the sensitivity of growing follicles to FSH. Thus, AMH may be an important modulator of female infertility and ovarian reserve; however, the mechanisms regulating AMH remain unclear.To evaluate AMH levels in the absence of H19 lncRNA, H19 knockout (H19KO) mice were evaluated for analysis of ovarian AMH gene expression, protein production, and reproductive function, including assessment of follicle numbers and litter size analysis. To further investigate regulation of AMH by the H19/let-7 axis, let-7 binding sites on AMH were predicted, and in vitro studies of the effect of H19 knockdown/overexpression with let-7 rescue were performed. Lastly, response to superovulation was assessed via oocyte counts and estradiol measurements.The H19KO mouse demonstrates subfertility and accelerated follicular recruitment with increased spontaneous development of secondary, preantral and antral follicles. Ovaries of H19KO mice have decreased AMH mRNA and protein, and AMH mRNA has a functional let-7 binding site, suggesting a plausible ncRNA-mediated mechanism for AMH regulation by H19/let-7. Lastly, in the absence of H19, superovulation results in higher estradiol and more oocytes, suggesting that H19 functions to limit the number of follicles that mature, produce estradiol, and ovulate. Thus, AMH's inhibitory actions are regulated at least in part by H19, likely via let-7, marking this ncRNA pair as important regulators of the establishment and maintenance of the follicular pool.

Patients with severe intraperitoneal bleeding had a lower body mass index, a history of surgery, were younger, and had a moderate ovarian response; those with mild bleeding were young and had a high ovarian response.

No abstract

The steroidogenic acute regulatory protein (STAR) governs the rate-limiting step in steroidogenesis, and its expression varies depending on the needs of the specific tissue. It is well known that tight control of steroid production is essential for multiple processes involved in reproduction. We recently showed that Star is regulated at the posttranscriptional level in vitro by H19 and let-7. Here we demonstrate that this novel regulatory mechanism is functional in vivo,

Background and AimEndoscopic examination of gastric atrophy has been developed to determine the extent of atrophy by identifying the atrophic border of gastric mucosa, but its value in predicting the risk of developing gastric neoplasms is not quantified. Thus, this systematic review and meta‐analysis aim to assess the incidence risk of gastric neoplasms on the basis of endoscopic grading of gastric atrophy.MethodsTwo authors independently searched the electronic databases (PubMed, Embase, and the Cochrane Library) from inception through December 31, 2019, without language restriction. The effect size on study outcomes is calculated using random‐effects model and presented as risk ratio (RR) with 95% confidence interval (CI). Heterogeneity, publication bias, and quality of included studies were also assessed.ResultsFourteen retrospective studies are identified to perform systematic review and meta‐analysis, 11 were cohort studies, and three were cross‐sectional research. The pooled RR for developing gastric neoplasms is 3.89 (95% CI 2.92–5.17) among general patients with severe endoscopic atrophy. For patients who underwent endoscopic resection for early gastric neoplasms, nearly two times increased risk of synchronous or metachronous neoplasms is pooled (RR = 1.96, 95% CI 1.39–2.75). In terms of the type of endoscopic atrophy, patients with open‐type endoscopic atrophy have a higher risk of gastric cancer development (RR 8.02; 95% CI 2.39–26.88) than those with close type. [Correction added on 22 December 2020, after first online publication: ‘(RR = 7.27; 95% CI 1.64–32.33)’ has been corrected to ‘(RR 8.02; 95% CI 2.39–26.88)’]ConclusionsGrading endoscopic atrophy according to the Kimura–Takemoto classification can assess the risk of gastric neoplasia development. Patients with severe or open‐type endoscopic gastric atrophy at baseline should undergo rigorous surveillance to early detect premalignant lesions and cancer.