Diffuse myometrium thinning and placenta accreta spectrum in a patient with systemic lupus erythematosus (SLE): a case report and review of the literature.

BACKGROUND: Cases of uterine wall thinning and placental abnormalities complicated with systemic lupus erythematosus (SLE) during pregnancy have been reported in Asian countries for ten years. Long-term steroid use can cause muscle degeneration, but the mechanism of myometrium thinning was not known. Through the review of published articles, this report is the first review of cases to discuss the pathogenesis and clinical features of thinned myometrium and placenta accreta spectrum (PAS) in pregnant patients with SLE. CASE PRESENTATION: A twenty-nine-year-old primigravida with a history of lupus enteritis and paralytic ileus had a natural conception after less than two years of steroid treatment. An ultrasonographic study showed a thin uterine wall with a widespread thick placenta on the entire surface of the uterine cavity in the third trimester. At the 39th gestational week, she underwent a cesarean section due to the failure of the uterus to contract, even though the injection of oxytocin. There were several engorged vessels on the surface of the anterior uterine wall at the time of laparotomy. We decided to perform a hysterectomy because diffuse PAS replaced her uterus. CONCLUSION: A review of reported cases and our case shows an unusual complication of SLE that might be related to the particular condition of the estrogen-mediated immune system. Clinicians should always pay attention to the possibility of uterine wall thinning as uterine atony and the structural abnormality of the placenta for SLE patients with the unscarred uterus.

Involvement of BMP-15 in glucocorticoid actions on ovarian steroidogenesis by rat granulosa cells.

To elucidate the impact of glucocorticoids on ovarian steroidogenesis and its molecular mechanism by focusing on bone morphogenetic proteins (BMPs), we examined the effect of dexamethasone (Dex) on estradiol and progesterone synthesis by using primary culture of rat granulosa cells. It was revealed that Dex treatment dose-dependently decreased estradiol production but increased progesterone production induced by follicle-stimulating hormone (FSH) by granulosa cells. In accordance with the effects of Dex on estradiol synthesis, Dex suppressed P450arom mRNA expression and cAMP synthesis induced by FSH. Dex treatment in turn enhanced basal as well as FSH-induced levels of mRNAs encoding the enzymes for progesterone synthesis including P450scc and 3ßHSD but not StAR and 20αHSD. Of note, Dex treatment significantly upregulated transcription of the BMP target gene Id-1 and Smad1/5/9 phosphorylation in the presence of BMP-15 among the key ovarian BMP ligands. It was also found that Dex treatment increased the expression level of BMP type-I receptor ALK-6 among the type-I and -II receptors for BMP-15. Inhibitory Smad6/7 expression was not affected by Dex treatment. On the other hand, BMP-15 treatment upregulated glucocorticoid receptor (GR) expression in granulosa cells. Collectively, it was revealed that glucocorticoids elicit differential effects on ovarian steroidogenesis, in which GR and BMP-15 actions are mutually enhanced in granulosa cells.

Surgically treated genital chronic graft-versus-host disease in women: A report of three cases.

Hematopoietic stem cell transplantation (HSCT) is a crucial treatment for hematological malignancy. Gonadal dysfunction occurs at an early stage after this treatment, and such patients may require hormone replacement therapy. Genital chronic graft-versus-host disease is a lesser-known complication of HSCT that begins with vulvar discomfort and dysuria and progresses to sexual dysfunction and retention of menstrual blood due to vaginal stenosis and obstruction; thus, significantly impairing the patient's quality of life. We describe three women who underwent vaginal reconstruction because of genital chronic graft-versus-host disease. We discuss the surgical techniques, including double cross plasty that were performed in each case. Surgical interventions enabled the continuation of HRT and facilitated sexual intercourse. In conclusion, gynecologists should be aware that genital chronic graft-versus-host disease can occur after HSCT, and that surgical treatment options are available to improve patients' symptoms and quality of life.

Adenosine Deaminase Family Acting on RNA 1 (ADAR1) May Be a De Novo Target for Endometriosis Treatment.

BACKGROUND/AIM: Adenosine deaminase family acting on RNA 1 (ADAR1) expression was examined to determine its correlation with endometriosis. The biological functions and inhibitory effects of ADAR1 knockdown were investigated in a human endometriotic cell line. MATERIALS AND METHODS: ADAR1 was examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR), and the apoptotic expression of ADAR1 small interfering RNA (siRNA) was confirmed using flow cytometry. The biological functions and inhibitory effects of ADAR1 knockdown were investigated using RT-PCR in a 12Z immortalized human endometriotic cell line. RESULTS: ADAR1 expression was significantly higher in patients with endometriosis than in those without (p<0.001). ADAR1 siRNA increased early and late apoptosis, compared to the mock (24.83%) and control (19.96%) cells. ADAR1 knockdown led to apoptosis through MDA5, RIG-I, IRF3, IRF7, caspase 3, caspase 7, and caspase 8 expression in the cell lines. CONCLUSION: ADAR1 is a potential novel therapeutic target in endometriosis.

Aldosterone enhances progesterone biosynthesis regulated by bone morphogenetic protein in rat granulosa cells.

Aldosterone (Aldo) is involved in various cardiovascular diseases such as hypertension and heart failure. Aldo levels are known to be increased in patients with polycystic ovary syndrome, and expression of the mineralocorticoid receptor (MR) has also been detected in the ovary. However, the effect of Aldo on reproductive function has yet to be elucidated. Here, we examined the effects of Aldo on follicular steroidogenesis using primary culture of rat granulosa cells by focusing on the ovarian bone morphogenetic protein (BMP) system acting as a luteinizing inhibitor. We found that Aldo treatment increased FSH-induced progesterone production in a concentration-responsive manner. Consistent with the effects on steroidogenesis, Aldo increased mRNA levels of progesterogenic factor and enzymes including StAR and P450scc, whereas Aldo failed to change FSH-induced estradiol and cAMP synthesis or P450arom expression by granulosa cells. Progesterone production and StAR expression induced by FSH and Aldo were reversed by co-treatment with spironolactone, suggesting the involvement of geonomic MR action. Aldo treatment attenuated Smad1/5/9 phosphorylation and Id1 transcription induced by BMP-6. Furthermore, Aldo enhanced the expression of inhibitory Smad6 in the presence of BMP-6. In addition, BMP-6 downregulated MR expression, while Aldo modulated the mRNA levels of endogenous BMP-6 and BMP type-II receptors, indicating the existence of a feedback loop between the BMP system and MR in granulosa cells. 　Collectively, the results indicated that Aldo predominantly enhances FSH-induced progesterone production by inhibiting BMP-Smad signaling, suggesting a novel role of Aldo in ovarian steroidogenesis and a functional link between MR and BMP pathways in granulosa cells.