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Receptive endometrium is a prerequisite for successful embryo implantation, and it follows that poor endometrial receptivity is a leading cause of implantation failure. miRNAs play important roles as epigenetic regulators of endometrial receptivity and embryo implantation through post-transcriptional modifications. However, the mechanisms of action of many miRNAs are poorly understood. In this study, we investigated the role of the miR-183 family, comprising three miRNAs (miR-183-5p, miR-182-5p, and miR-96-5p) in endometrial receptivity and embryo implantation. The miR-183 family shows estrogen-dependent upregulation in endometrial Ishikawa (IK) cells. The miR-183 family also has a positive role in migration and proliferation of IK cells. Furthermore, JAr spheroid attachment experiments show that attachment rates were significantly decreased after treatment of IK cells with inhibitors for miR-183-5p and miR-182-5p and increased after treatment with miR-183-5p-mimic and miR-96-5p-mimic, respectively. The downstream analysis shows that catenin alpha 2 (CTNNA2) is a potential target gene for miR-183-5p, and this was confirmed in luciferase reporter assays. An in vivo mouse pregnancy model shows that inhibition of miR-183-5p significantly decreases embryo implantation rates and increases CTNNA2 expression. Downregulation of CTNNA2 in endometrial cells by miR-183-5p may be significant in mediating estrogenic effects on endometrial receptivity. In conclusion, miR-183-5p and the CTNNA2 gene may be potential biomarkers for endometrial receptivity and may be useful diagnostic and therapeutic targets for successful embryo implantation.

Gestational and postpartum high‐fat diets (HFDs) have been implicated as causes of obesity in offspring in later life. The present study aimed to investigate the effects of gestational and/or postpartum HFD on obesity in offspring. We established a mouse model of HFD exposure that included gestation, lactation and post‐weaning periods. We found that gestation was the most sensitive period, as the administration of a HFD impaired lipid metabolism, especially fatty acid oxidation in both foetal and adult mice, and caused obesity in offspring. Mechanistically, the DNA hypermethylation level of the nuclear receptor, peroxisome proliferator‐activated receptor‐α (Pparα), and the decreased mRNA levels of ten‐eleven translocation 1 (Tet1) and/or ten‐eleven translocation 2 (Tet2) were detected in the livers of foetal and adult offspring from mothers given a HFD during gestation, which was also associated with low Pparα expression in hepatic cells. We speculated that the hypermethylation of Pparα resulted from the decreased Tet1/2 expression in mothers given a HFD during gestation, thereby causing lipid metabolism disorders and obesity. In conclusion, this study demonstrates that a HFD during gestation exerts long‐term effects on the health of offspring via the DNA demethylation of Pparα, thereby highlighting the importance of the gestational period in regulating epigenetic mechanisms involved in metabolism.

Objective This study aimed to determine the effects of diet-induced paternal obesity on cognitive function in mice offspring. Methods Male mice (F0) were randomized to receive either a control diet (10 kcal% fat) or a high-fat diet (HFD; 60 kcal% fat) for 10 weeks before being mated with normal females to generate F1 offspring. Male F1 offspring were mated with normal females to generate F2 offspring. Behavioral tests were used to assess cognitive functions in F1 and F2 offspring. Reduced representation bisulfite sequencing was used to the explore mechanisms of epigenetic inheritance. Results HFD-induced paternal obesity resulted in cognitive impairments in F1 offspring, potentially due, at least in part, to increased methylation of the BDNF gene promoter, which was inherited from F0 spermatozoa. BDNF/tyrosine receptor kinase B signaling was associated with cognitive impairments in HFD-fed F1 offspring. However, there were no significant changes in F2 offspring. Conclusions The findings provide evidence of intergenerational effects of paternal obesity on cognitive function in offspring occurring via epigenetic spermatozoan modifications.

Over the past four decades, the global prevalence of obesity has increased rapidly in all age ranges. Emerging evidence suggests that paternal lifestyle and environmental exposure have a crucial role in the health of offspring. Therefore, the current study investigated the impact of paternal obesity on the metabolic profile of offspring in a male mouse model of obesity. Female offspring of obese fathers fed a high-fat diet (HFD) (60% kcal fat) showed hyperglycemia because of enhanced gluconeogenesis and elevated expression of phosphoenolpyruvate carboxykinase (PEPCK), which is a key enzyme involved in the regulation of gluconeogenesis. Methylation of the Igf2/H19 imprinting control region (ICR) was dysregulated in the liver of offspring, and the sperm, of HFD fathers, suggesting that epigenetic changes in germ cells contribute to this father-offspring transmission. In addition, we explored whether H19 might regulate hepatic gluconeogenesis. Our results showed that overexpression of H19 in Hepa1-6 cells enhanced the expression of PEPCK and gluconeogenesis by promoting nuclear retention of forkhead box O1 (FOXO1), which is involved in the transcriptional regulation of Pepck. Thus, the current study suggests that paternal exposure to HFD impairs the gluconeogenesis of offspring via altered Igf2/H19 DNA methylation.

Background The existing reports about intergenerational or transgenerational effects of intrauterine hyperglycemia have included both intrauterine and postnatal metabolic exposure factors, while the impact of intrauterine hyperglycemia per se has not been assessed alone. A number of studies suggest DNA methylation reprogramming of gametes plays a crucial role in the metabolic inheritance, but it is unclear when and how DNA methylation patterns are altered when exposed to intrauterine hyperglycemia. In this study, we selected nondiabetic F1- and F2-gestational diabetes mellitus (GDM) male mice as founders to examine metabolic changes in the next generation and performed methylome sequencing of day 13.5 primordial germ cells (PGCs) from F1-GDM to explore the underlying epigenetic mechanism. Results We found that intrauterine hyperglycemia exposure resulted in obesity, insulin resistance, and/or glucose intolerance in F2 male mice, but no metabolic changes in F3 male mice at 8 weeks. Using reduced representation bisulfite sequencing, we found DNA methylome of day 13.5 PGCs from F1-GDM fetuses revealed differently methylated genes enriched in obesity and diabetes. Methylation validation of the insulin resistance and fat accumulation gene Fyn showed a consistent hypomethylation status in F1 PGCs, F1 fetal testes, sperm from F1/C-GDM mice, and somatic cells from F2-GDM male mice. In contrast, no methylation alteration was observed in F2-GDM male germ cells and F3-GDM somatic cells. Conclusion We provide evidence that intrauterine hyperglycemia exposure per se contributes to intergenerational metabolic changes in the F2 but not F3 generation. And the aberrant DNA methylation reprogramming occurs as early as day 13.5 in PGCs of the F1 generation. Our findings suggest that intrauterine exposure alone is sufficient to cause the epigenetic inheritance in F2 offspring, and the epigenetic memory carried by DNA methylation pattern could be erased by the second wave of methylation reprogramming in F2 PGCs during fetal development. Electronic supplementary material The online version of this article (10.1186/s13072-018-0192-2) contains supplementary material, which is available to authorized users.

// Tanzil Ur Rahman 1, 2, * , Kamran Ullah 1, 2, * , Zhang-Hong Ke 4 , Meng-Xi Guo 1, 2 , Lu-Yang Jin 1, 2 , Jun Ren 1, 2 , Yu-Zhong Zhou 1, 2 , Yi Cheng 1, 2 , Xin-Yan Dong 1, 2 , Hai-Yan Pang 1, 2 , Ting-Ting Wang 1 , Jian-Zhong Sheng 1, 2, 3 and He-Feng Huang 1, 3 1 The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China 2 Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China 3 The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 4 Center of Reproductive Medicine, Fujian Maternity and Children Health Hospital, Fujian Medical University, Fuzhou, China * These authors have contributed equally to this work Correspondence to: Jian-Zhong Sheng, email: shengjz@zju.edu.cn He-Feng Huang, email: huanghefg@hotmail.com Keywords: triglyceridemia, leptin, hypothalamus, neuropeptide Y, pSTAT3 Received: February 08, 2017 Accepted: May 10, 2017 Published: June 16, 2017 ABSTRACT Maternal obesity influence the child’s long-term development and health. Though, the mechanism concerned in this process is still uncertain. In the present study, we explored whether overfeeding of a high-fat diet during pregnancy in female rats altered metabolic phenotypes in an F1 generation and authenticated the contribution of hypothalamic leptin signaling. Leptin responsiveness and the number of immunopositive neurons for phosphorylated signal transducer and activator transcription 3 (pSTAT3) were analyzed. Neuropeptide Y in the arcuate nucleus of the hypothalamus and in nucleus tractus solitaries was examined. Triglycerides and leptin levels were increased in the high-fat diet mother. The number of neuropeptide Y positive cell bodies and neurons was significantly increased in the high-fat diet-F1 offspring (HDF-F1) as compared to Chow-F1. Leptin administration significantly decreased the food intake and increased the pSTAT3 expression levels in neurons in the arcuate nucleus of Chow-F1. However, leptin did not show any effect on food intake and had a reduced effect on pSTAT3 expression levels in neurons in the arcuate nucleus of HDF-F1. From the present domino effect, we conclude that mothers exposed to high-fat diet during pregnancy may pass the obese phenotype to the succeeding generation via altering hypothalamic leptin signaling.

To investigate the effects of soy isoflavones (SI) on the expression of estrogen receptor-α (ER-α) in senile rat ovaries and ovarian granulosa cell cultured in vitro treated with genistein, a major active component of SI.The animal model of perimenopause rats was established by unforced aging. The animals were treated by intragastric administration (ig) with low (50 mg/kg), middle (158 mg/kg) and high (500 mg/kg) dose of SI for 8 weeks. The expressions of ER-α mRNA and protein were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The granulosa cells of rat ovaries were isolated and administered with genistein (0, 0.1, 1, 5, 10, 100 µmol/L) for 48 h and the expression levels of ER-α mRNA detected by RT-PCR.The ER-α mRNA expression levels of the low, middle and high dose groups of SI (0.207 ± 0.014, 0.316 ± 0.073 and 0.402 ± 0.170 respectively) were higher than those of the model group (0.671 ± 0.170) (all P0.01). The expression levels of ER-α protein for the low, middle and high dose groups of SI (7.35 ± 4.90, 13.90 ± 5.12 and 23.79 ± 10.31 respectively) were higher than those of the model group (2.74 ± 0.09) (all P0.01). The expression levels of ER-α mRNA in granulosa cells treated with 1, 5, 10 µmol/L genistein for 48 h were 0.927 ± 0.232, 1.067 ± 0.154, 1.118 ± 0.126 respectively (all P0.01). They were higher than those of the control group (0.671 ± 0.170). But the expression levels of 100 µmol/L genistein group were lower than those of the control group (P0.05).Soy isoflavones can up-regulate the expressions of ER-α mRNA and protein in senile rat ovaries. As a major active component of soy isoflavones, genistein can regulate the expressions ER-α mRNA in granulosa cells of rat ovaries. Such an effect is concentration-dependent. And 1-10 µmol/L genistein may up-regulate the expression of ER-α mRNA.

The contents of Indium in smelting waste for extract Indium has been determined by the method of flame-emitting. The requirement of determination, factors of influence have been studied. The result by this method has been contrasted to FAAS. The method is sensitive and has good precision and accuracy. The detection limit was 0.016 microgram.mL-1, the relative standard deviation was 1.1%.