Objective-Hypothesizing that levels of 25OH-D in body fluids are reflective of vitamin repletion status, we aimed to determine if 25OH-D levels in the follicular fluid (FF) of infertile women undergoing in vitro fertilization (IVF) demonstrate a relationship with IVF cycle parameters and outcome. Design-Prospective Cohort study Setting-Academic tertiary care center Patients-84 infertile women undergoing IVFInterventions-FF from follicles ≥14mm; serum (n=10) and FF levels of 25OH-D Main outcome measures-Clinical pregnancy (CP) (defined as evidence of intrauterine gestation sac on ultrasound) following IVF; IVF cycle parameters.Results-Serum and FF levels of 25OH-D were highly correlated (r=0.94, p<0.001). In a predominantly Caucasian population (66%), significantly lower FF 25OH-D levels were noted in Black versus non-Black patients (p=0.001). Significant inverse correlations were seen between FF 25OH-D levels and BMI (r−0.25, p=0.035). Significantly higher CP and implantation rates were observed across tertiles of FF25OH-D (p=0.029 and p=0.041 respectively); patients achieving CP following IVF (n=26) exhibited significantly higher FF levels of 25OH-D (p=0.005). Multivariable logistic regression analysis confirmed FF 25OH-D levels as an independent predictor to success of an IVF cycle; adjusting for age, BMI, ethnicity and number of embryos transferred (ET) each ng/ml increase in FF 25OH-D increased the likelihood for achieving CP by 6% (p=0.030). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-Our findings that women with higher vitamin D level in their serum and FF are significantly more likely to achieve CP following IVF-ET are novel. A potential for benefit of vitamin D supplementation on treatment success in infertile patients undergoing IVF is suggested that merits further investigation. NIH Public Access

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(1) Neurogenesis driven by neural stem cells (NSCs) is regulated by physiological and pathological factors. Melatonin (MT) has profound neurotrophic and neuroprotective effects. Hence, we studied the role of MT in regulating the viability and differentiation of NSCs derived from rat ventral midbrain. (2) NSCs were isolated from the rat ventral midbrain. The viability of NSCs was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-ulfophenyl)-2H-tetrazolium assay. The differentiation of NSCs was examined by analyzing the expression of the neural markers, MT receptors, brain derived neurotropic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) with semi-quantitative RT-PCR, immunofluorescence cytochemistry, and Western blot. (3) Our results showed that MT could promote the viability of NSCs. In addition, MT could significantly elevate the mRNA and protein levels of tyroxine hydroxylase (TH), a marker of dopaminergic neurons, and decrease the expression of the astrocytes maker glial fibrillary acidic protein (GFAP). MT also increased the production of BDNF and GDNF in the cultured NSCs. Meanwhile, we first found that two subtypes of MT receptors, MT1 and MT2, were expressed in the ventral midbrain NSCs. (4) These results demonstrated that MT could induce NSCs to differentiate into dopaminergic neurons and decrease astrocyte production. These findings also suggest that MT could offer a beneficial tool in guiding directional differentiation of NSCs.

Reproductive success depends on a robust and appropriately timed preovulatory LH surge. The LH surge, in turn, requires ovarian steroid modulation of GnRH neuron activation by the neuropeptide kisspeptin and glutamate and gamma-aminobutyric acid (GABA) neurotransmission in the medial preoptic area (mPOA). Middle-aged females exhibit reduced excitation of GnRH neurons and attenuated LH surges under estrogen-positive feedback conditions, in part, due to increased GABA and decreased glutamate neurotransmission in the mPOA. This study tested the hypothesis that altered kisspeptin regulation by ovarian steroids plays a role in age-related LH surge dysfunction. We demonstrate that middle-aged rats exhibiting delayed and attenuated LH surges have reduced levels of Kiss1 mRNA in the anterior hypothalamus under estrogen-positive feedback conditions. Kisspeptin application directly into the mPOA rescues total LH release and the LH surge amplitude in middle-aged rats and increases glutamate and decreases GABA release to levels seen in the mPOA of young females. Moreover, the N-methyl-D-aspartate receptor antagonist MK801 blocks kisspeptin reinstatement of the LH surge. These observations suggest that age-related LH surge dysfunction results, in part, from reduced kisspeptin drive under estrogen-positive feedback conditions and that kisspeptin regulates GnRH/LH release, in part, through modulation of mPOA glutamate and GABA release.

Astragalus polysaccharides (APS), one of main bioactive components in Astragalus membranaceus Bunge, has been reported to possess anti-inflammatory activities, but the molecular mechanisms behind this activity are largely unknown. This study aimed to investigate expression of inflammatory cytokines and the MAPK/NF-κB pathway in human THP-1 macrophages induced by lipopolysaccharide (LPS). The results showed that the concentrations of TNF- and IL-1β released from LPS stimulated THP-1 cells increased significantly compared to control (p < 0.01). After treatment with APS, the TNF- and IL-1β levels were significantly lower than those in the LPS group (p < 0.05). The mRNA expression of TNF- and IL-1β were also inhibited. Mechanistic studies indicated that APS strongly suppressed NF-κB activation and down-regulated the phosphorylation of ERK and JNK, which are important signaling pathways involved in the production of TNF- and IL-1β, demonstrating that APS could suppress the production of TNF- and IL-1β by LPS stimulated macrophages by inhibiting NF-κB activation and ERK and JNK phosphorylation.