Berberine alleviates inflammation in polycystic ovary syndrome by inhibiting hyaluronan synthase 2 expression.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous metabolic and endocrine disorder that causes anovulatory infertility and abnormal folliculogenesis in women of reproductive age. Several studies have revealed inflammation in PCOS follicles, and recent evidence suggests that Berberine (BBR) effectively reduces inflammatory responses in PCOS, however, the underlying mechanisms remain unclear. PURPOSE: To determine the underlying mechanisms by which BBR alleviates inflammation in PCOS. STUDY DESIGN: Primary human GCs from healthy women and women with PCOS, and KGN cells were used for in vitro studies. ICR mice were used for in vivo studies. METHODS: Gene expression was measured using RT-qPCR. HAS2, inflammatory cytokines, and serum hormones were assayed by ELISA. Protein expression profiles were assayed by Western blot. Chronic low-grade inflammatory mouse models were developed by intraperitoneal injection with LPS, and PCOS mouse models were established by subcutaneous intraperitoneal injection of DHEA. BBR and 4-MU were administered by gavage. Ovarian morphologic changes were evaluated using H&E staining. HAS2 expression in the ovary was assayed using Western blot and immunohistochemistry. RESULTS: Our results confirmed that HAS2 expression and hyaluronan (HA) accumulation are closely associated with inflammatory responses in PCOS. Data obtained from in vitro studies showed that HAS2 and inflammatory genes (e.g., MCP-1, IL-1ß, and IL-6) are significantly upregulated in PCOS samples and LPS-induced KGN cells compared to their control groups. In addition, these effects were reversed by blocking HAS2 expression or HA synthesis using BBR or 4-MU, respectively. Furthermore, HAS2 overexpression induces the expression of inflammatory genes in PCOS. These results were further confirmed in LPS- and DHEA-induced mouse models, where inflammatory genes were reduced by BBR or 4-MU, and ovarian morphology was restored. CONCLUSIONS: Our results define previously unknown links between HAS2 and chronic low-grade inflammation in the follicles of women with PCOS. BBR exerts its anti-inflammatory effects by down-regulating HAS2. This study provides a novel therapeutic target for alleviating ovarian inflammation in women with PCOS.

Intrauterine administration of hCG-activated autologous human peripheral blood mononuclear cells (PBMC) promotes live birth rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure.

Recurrent implantation failure refers to unsuccessful implantation after repeated transfers of morphologically good quality embryos into a normal uterus. Recently, accumulating evidence has suggested that local immune cells at the implantation site have actively contributed to embryo implantation. Our aim was to study the effects of intrauterine administration of hCG-activated autologous human PBMC on clinical pregnancy, implantation rates and live birth rate of patients who received frozen/thawed embryo transfer. We observed patients with one to three failed transplantations cannot benefit from the administration, but the rate of clinical pregnancy (39.58% vs. 14.29%), live birth (33.33% vs. 9.58%) and implantation (22.00% vs. 4.88%) were significantly increased in patients with four or more failures, respectively. For patients with endometrial thickness more than 7mm and less than 8mm on day of embryo transfer, the implantation rate (22.69% vs. 14.21%) and the live birth rate significantly higher in the PBMC-treated group; For patients who had RIF and received frozen/thawed early cleavage stage embryo transfer, the live birth delivery rate (29.63% vs. 13.33%) significant higher in PBMC-treated group. These findings indicate that intrauterine administration of hCG-activated autologous PBMC effectively improves the IVF outcomes for RIF patients, especially for the RIF patients with cleavage stage embryo transfer, patients with thin endometrial thickness also benefit from this approach.

Folic acid supplementation as adjunctive treatment premature ejaculation.

Selective serotonin re-uptake inhibitors (SSRIs), has been increasingly used for the treatment of premature ejaculation over the past 5 years. It was reported that folic acid plays important roles in synthesis of 5-HT. Therefore, we hypothesize that folic acid supplementation may cures premature ejaculation by the same mechanism of interacting with monoamine neurotransmitters in brain, to be the replacement of RRSIs. Folic acid supplementation cures premature ejaculation more safely. These new views will help to understand the diagnosis and treatment methods for premature ejaculation.