Anti-SPP1 monoclonal antibody, clone 25D19

STUDY QUESTION: Is the phosphoinositol 1,3-kinase/protein kinase B (PI3K/AKT) pathway expression profile in cumulus cells (CCs) a potential marker of oocyte competence and predictive of pregnancy outcome? SUMMARY ANSWER: Eleven genes (AKT1, ARHGEF7, BCL2L1, CCND1, E2F1, HRAS, KCNH2, PIK3C2A, SHC1, SOS1 and SPP1) in the PI3K/AKT pathway were significantly down-regulated in CCs from oocytes that went on to produce a pregnancy compared to CCs associated with a negative outcome. WHAT IS KNOWN ALREADY: The PI3K/AKT pathway plays a pivotal role in the interdependence and continuous feedback between the oocyte and CCs. STUDY DESIGN SIZE, DURATION: The expression analysis of 92 transcripts in the PI3K/AKT pathway in CCs from patients with negative or positive pregnancy outcome, after single embryo transfer, was performed. Mouse CCs target gene expression was conducted to associate the expression profile of PI3K/AKT pathway to oocyte developmental profile. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifty-five good prognosis IVF patients who had been referred to IVF or intracytoplasmic sperm injection treatment for male-factor infertility or tubal disease were enroled. CCs from single cumulus-oocyte complexes (COCs) from 16 patients who underwent a single embryo transfer were analyzed. Twenty-five CD-1 mice were used to assess gene expression in CCs associated with oocytes with different competence in relation to hCG priming. A total 220 human COCs were collected. The RNA extracted from CCs of 16 selected patients was used to analyze PI3K/AKT pathway gene expression employing a 96-well custom TaqMan Array. Expression data of CCs associated to positive IVF outcome were compared to data from negative outcome samples. Mice were sacrificed after 9, 12, 15, 21 and 24 h post-hCG administration to obtain CCs from MII oocytes with different developmental competence. Akt1, Bcl2l2 and Shc1 expression were tested in the collected mouse CCs. In addition, the expression of upstream regulator ESR1, the gene encoding for the oestrogen receptor ER beta, and the downstream effectors of the pathway FOXO1, FOXO3 and FOXO4 was evaluated in human and mouse samples. MAIN RESULTS AND THE ROLE OF CHANCE: Transcripts involved in the PI3K Signaling Pathway were selectively modulated according to the IVF/ICSI outcome of the oocyte. Eleven transcripts in this pathway were significantly down-regulated in all samples of CCs from oocytes with positive when compared those with a negative outcome. These outcomes were confirmed in mouse CCs associated with oocytes at different maturation stages. Expression data revealed that the down-regulation of ESR1 could be related to oocyte competence and is likely to be the driver of expression changes highlighted in the PI3K/AKT pathway. LIMITATIONS REASONS FOR CAUTION: Small sample size and retrospective design. WIDER IMPLICATIONS OF THE FINDINGS: The CCs expression profile of PI3K/AKT signaling genes, disclosed a specific CCs gene signature related to oocyte competence. It could be speculated that CCs associated with competent oocytes have completed their role in sustaining oocyte development and are influencing their fate in response to metabolic and hormonal changes by de-activating anti-apoptotic signals.

The incidence of type 1 diabetes (T1D) and its associated risks of chronic kidney disease or end-stage renal disease development are on the rise. T1D is an autoimmune disease in which insulin-producing beta cells are destroyed. Increased incidence of T1D has been suggested to be a result of environmental factors such as exposure to polycyclic aromatic hydrocarbons (PAHs). 2-aminoanthracene (2AA) is a PAH that has been associated with the onset of early diabetic symptoms. This study was conducted to assess if 2AA dietary ingestion would induce T1D renal injuries. To accomplish study goals, Sprague-Dawley rats were assigned into three 2AA dietary (0, 50, and 100 mg/kg-2AA) ingestion groups for 12 weeks. Animals were evaluated for various morphometric indices, clinical markers, and gene expression. The rats in the 100 mg/kg group lost 5% less weight than the other treatment groups and converted roughly 3% more of their food intake into body mass. Renal histopathology indicated no significant difference between groups. The kidney weight per bodyweight of the 100 mg/kg treatment group was 30.1% greater than the control group. Creatinine concentration of the 100 mg/kg group was 46.2% greater than the control group. Serum glucose levels were significantly elevated in rats exposed to 2AA. On the contrary, serum albumin concentration was significantly reduced in 2AA-treated rats. T1D and genetic markers of renal injury such as FABP1, SPP1, IL-1B, and IL-7 were elevated in treated groups. These results suggest that 2AA may induce the early diabetic renal injuries.