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Background & Aim: Shortage of donor hepatocytes limits hepatocyte transplantation for clinical application. Induced hepatic stem cells (iHepSCs) have capacities of self‐renewal and bipotential differentiations. Here, we investigated whether iHepSCs could be extensively expanded, and whether they could differentiate into sufficient functional hepatocytes as donors for transplantation therapy after their extensive expansions. Methods: Murine extensively expanded iHepSCs (50‐55 passages) were induced to differentiate into iHepSC‐Heps under a chemically defined condition. iHepSC‐Heps were proved for carrying morphological hepatocyte characters and hepatocytic functions including low‐density lipoprotein uptake, glycogen storage, CLF secretion, ICG uptake and release, Alb secretion, urea synthesis and metabolism‐relative gene expressions respectively. Next, both iHepSCs and iHepSC‐Heps were transplanted into Fah‐/‐ mice respectively. Both liver repopulation and alleviation of liver function were compared between two transplantation groups. Results: Murine iHepSCs still maintained the capacities of self‐renewal and bipotential differentiations after extensive expansion. The efficiency for the functional hepatocyte differentiation from extensively expanded iHepSCs reached to 72.64%. Transplantations of both extensively expanded iHepSCs and iHepSC‐Heps resulted in liver engraftment in Fah‐/‐ mice. Survival rate of Fah‐/‐ mice recipients and level of liver repopulation were 50% and 20.32 ± 4.58% respectively in iHepSC‐Heps group, while 33% and 10.4 ± 4.3% in iHepSCs group. Conclusions: Extensively expanded iHepSCs can efficiently differentiate into hepatocytes in chemical defined medium. Transplantation of iHepSC‐Heps was more effective and more efficient than transplantation of iHepSCs in Fah‐/‐ mice. Our results suggested an innovative system to obtain sufficient hepatocytes through hepatic differentiation of iHepSCs generated by lineage reprogramming. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to investigate the potential role of IL-10 in regulating the receptivity marker HOXA10 in the endometrium of women with adenomyosis. Methods. The expression levels of IL-10, HOXA-10, STAT3, and p-STAT3 in the endometrium of women with adenomyosis and controls were examined by means of western blotting and immunohistochemistry. The expression of the HOXA10 protein in Ishikawa cells treated with rIL-10 was examined by western blotting. The attachment rate of BeWo cell spheroids to Ishikawa cells treated with rIL-10 was expressed as a percentage of the total number of spheroids. Results. The expression levels of HOXA10 and IL-10 in the adenomyosis group were significantly lower than those in the control group, and there was a positive correlation between HOXA10 and IL-10 protein levels in all the women examined. rIL-10 increased HOXA10 expression in a concentration- and time-dependent manner by inducing the phosphorylation of STAT3 in Ishikawa cells. Treatment with rIL-10 promoted the attachment of BeWo spheroids to Ishikawa cells, which was reversed by the inhibition of STAT3 phosphorylation. The expression of p-STAT3 in the adenomyosis group was significantly lower than that in the control group, and there was a positive correlation between IL-10 and p-STAT3 protein levels in all the women examined. Conclusions. Both IL-10 and HOXA10 levels in the endometrium are significantly reduced in women with adenomyosis compared with those in control women. The phosphorylation of STAT3 has been proven to be a critical mediator between IL-10 and HOXA10, which may play critical roles in embryo implantation. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine, metabolic and heterogeneous disorder in women of reproductive age, the exact etiology of which remains unknown. To unravel the molecular mechanisms underlying the hyperandrogenic phenotype of PCOS, prenatally androgenized (PNA) mice were used to mimic this phenotype in women with PCOS. Using microarray analysis, 1188 differentially expressed genes, including 671 upregulated and 517 downregulated genes, were identified in ovaries from PNA mice. Five differentially expressed genes (Aldh1a7, Bhmt, Mtr, Nrcam, Ptprg) were validated, and decreased MTR expression was shown in ovaries of PNA mice. In addition, results from qRT-PCR showed decreased MTR expression in granulosa cells (GCs) from women with the hyperandrogenic phenotype of PCOS. Serum levels of S-adenosyl methionine (SAM), the downstream product of MTR, were also decreased in PNA mice and women with the hyperandrogenic phenotype of PCOS. Our study provides evidence that the hyperandrogenic phenotype of PCOS is linked to abnormal folate one-carbon metabolism. [ABSTRACT FROM AUTHOR]

Chemotherapy treatment in women can frequently cause damage to the ovaries, which may lead to primary ovarian insufficiency (POI). In this study, we assessed the preventative effects of hyaluronic acid (HA) in immunosuppressive drug-induced POI-like rat models and investigated the possible mechanisms. We found that HA, which was reduced in primary and immunosuppressant-induced POI patients, could protect the immunosuppressant-induced damage to granulosa cells (GCs) in vitro. Then we found that HA blocked the tripterygium glycosides (TG) induced POI-like presentations in rats, including delayed or irregular estrous cycles, reduced 17 beta-estradiol(E2) concentration, decreased number of follicles, destruction of follicle structure, and damage of reproductive ability. Furthermore, we investigated the mechanisms of HA prevention effects on POI, which was associated with promotion of GC proliferation and PGRMC1 expression. In conclusion, HA prevents chemotherapy-induced ovarian damage by promoting PGRMC1 in GCs. This study may provide a new strategy for prevention and treatment of POI. [ABSTRACT FROM AUTHOR]