Altered thyroid hormone profile in offspring after exposure to high estradiol environment during the first trimester of pregnancy: a cross-sectional study.

BACKGROUND: The increasing number of babies conceived by in vitro fertilization and embryo transfer (IVF-ET) shifts concern from pregnancy outcomes to long-time health of offspring. Maternal high estradiol (E2) is a major characteristic of IVF-ET and lasts throughout the first trimester of pregnancy. The fetal thyroid develops during this period and may thus be affected by exposure to the supra-physiological E2. The aim of this study is to investigate whether the high E2 maternal environment in the first trimester increases the risk of thyroid dysfunction in children born following IVF-ET. METHODS: A cross-sectional survey design was used to carry out face-to-face interviews with consecutive children attending the hospital. A total of 949 singletons born after fresh embryo transfer (ET) (n=357), frozen ET (n=212), and natural conception (NC) (n=380), aged 3 to 10 years old, were included. All children were thoroughly examined. Meanwhile, another 183 newborns, including 55 fresh ET, 48 frozen ET, and 80 NC were studied. Levels of serum T3, FT3, T4, FT4, and TSH and levels of maternal E2 at different stages of the first trimester were examined. RESULTS: The mean serum E2 levels of women undergoing fresh ET during the first trimester of pregnancy were significantly higher than those of the women undergoing frozen ET or following NC. The thyroid hormone profile, especially the levels of T4, FT4, and TSH, were significantly increased in 3- to 10-year-old children conceived by fresh ET compared to NC. The same tendency was confirmed in newborns. However, levels of T4 and TSH in the frozen ET group were nearer to that of the NC group. Furthermore, levels of T4 and FT4 in fresh ET were positively correlated with maternal serum levels of E2 during early pregnancy. CONCLUSIONS: The maternal high E2 environment in the first trimester is correlated with increased risk of thyroid dysfunction. Frozen ET could reduce risks of thyroid damage in children conceived by IVF. Further studies are needed to confirm these findings and to better determine the underlying molecular mechanisms and clinical significance. TRIAL REGISTRATION: ChicCTR-OCC-14004682 (22-05-2014).

Altered protein expression profiles in umbilical veins: insights into vascular dysfunctions of the children born after in vitro fertilization.

Cardiovascular dysfunction and remodeling have been found in some children conceived by in vitro fertilization (IVF). However, the underlying mechanisms remain unclear. In this study, the retrospective investigation showed that the blood pressure of IVF-conceived Chinese children was higher than that of naturally conceived (NC) children at ages 3-13 yr. We analyzed the expression profile of proteins in the umbilical veins of IVF and NC newborns by proteomic techniques. Using iTRAQ (isobaric tags for relative and absolute quantitation), 47 differentially expressed proteins (DEPs) were identified by feature selection in IVF umbilical veins compared with NC. Ingenuity Pathway Analysis, which is used to explore the signaling pathways of DEPs, revealed that these DEPs played important roles in vascular system development and carbon metabolism, implying that these DEPs might be potential candidates for further exploration of the mechanism(s) of vascular dysfunction in IVF children. We found that the serum estradiol (E2) level in the cord blood of IVF newborns was significantly higher than that of NC newborns. High concentrations of E2 induced alteration of lumican and vimentin expression in human umbilical vein endothelial cells, which was consistent with the proteomic results. These findings suggested that abnormal expression of proteins in umbilical veins might be related to the cardiovascular dysfunction and remodeling in IVF offspring. In conclusion, our data for the first time reveal the protein expression profile in blood vessels of IVF offspring and provide information for further mechanism study and evaluation of risks of cardiovascular abnormality in IVF children.

Impact of the hepatic branch of the vagus and Roux-en-Y gastric bypass on the hypoglycemic effect and glucagon-like peptide-1 in rats with type 2 diabetes mellitus.

BACKGROUND: The impact of the hepatic branch of the vagus and Roux-en-Y gastric bypass (RYGB) on the hypoglycemic effect and glucagon-like peptide-1 (GLP-1) in rats with type 2 diabetes mellitus (T2DM) was investigated, and interactions were preliminarily analyzed. METHODS: A total of 45 rats with T2DM were divided into four groups: sham operation (S, n = 10), sham operation with the hepatic branch of the vagus resected (SV, n = 11), RYGB (n = 12), and RYGB without preservation of the vagus (RYGBV, n = 12). Body mass, fasting blood glucose (FBG), fasting serum insulin, and concentrations of fasting serum GLP-1 were examined in the first, second, fourth, and eighth week before and after surgery. The effects of RYGB and the hepatic branch of the vagus on GLP-1 levels in the eighth postoperative week were also analyzed. RESULTS: RYGB caused a significant reduction in the weight of rats with T2DM (P < 0.05), improved the levels of serum GLP-1 and insulin (P < 0.05), and decreased FBG level (P < 0.05). Retention of the hepatic branch of the vagus maintained weight reduction for a longer period (P < 0.05) and increased the levels of serum GLP-1 and insulin (P < 0.05), but had no impact on FBG level (P > 0.05). CONCLUSIONS: RYGB had better therapeutic efficacy in rats with T2DM. Care should be taken during RYGB surgery to preserve the hepatic branch of the vagus.

Maternal high-fat-diet exposure is associated with elevated blood pressure and sustained increased leptin levels through epigenetic memory in offspring.

Maternal metabolism dysregulation during pregnancy predisposes offspring to major diseases, including hypertension, in later life, but the mechanism involved remains to be fully elucidated. A high-fat-diet (HFD) pregnant rat model was used to investigate whether excessive intrauterine lipid exposure was associated with elevated blood pressure in offspring and increased levels of leptin, an important biomarker and mediator of vascular dysfunction and hypertension. We found that gestational hyperlipidemia predisposed offspring to blood pressure elevation and sustained increases in leptin levels with no difference in body weight in the rat model. Increased leptin expression and leptin promoter hypomethylation were found in adipose tissues of HFD-exposed offspring. The treatment of mesenchymal stem cells with free fatty acids during adipogenic differentiation resulted in increased leptin expression, accompanied by leptin promoter hypomethylation. In addition, we also followed up 121 children to evaluate the association between maternal triglyceride levels and offspring blood pressure. Consistent with the animal study results, we observed elevated serum leptin levels and blood pressure in the offspring born to women with gestational hypertriglyceridemia. Our findings provide new insights that maternal hyperlipidemia is associated with elevated blood pressure in offspring and is associated with increases in leptin levels through epigenetic memory.

Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis.

Basonuclin (BNC1) is expressed primarily in proliferative keratinocytes and gametogenic cells. However, its roles in spermatogenesis and testicular aging were not clear. Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree. In this study, we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging. Genome-wide expression profiling and direct binding studies (by chromatin immunoprecipitation sequencing) with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10 (Klhl10), testis expressed 14 (Tex14), and spermatogenesis and centriole associated 1 (Spatc1). Moreover, biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like (TAF7L), a germ cell-specific paralogue of the transcription factor IID subunit TAF7, both in vitro and in testis, suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis. The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex, thus, disturbing expression of related genes and leading to testicular premature aging. Similarly, expressions of BNC1, TAF7L, Y-box-binding protein 2 (YBX2), outer dense fiber of sperm tails 1 (ODF1), and glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) were significantly decreased in the testis of men with non-obstructive azoospermia. The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.

Comparison of Great Curvature Plication with Duodenal-Jejunal Bypass (GCP-DJB) and Sleeve Gastrectomy (SG) on Metabolic Indices and Gut Hormones in Type 2 Diabetes Mellitus Rats.

OBJECTIVE: The present study compared the therapeutic effects of great curvature plication with duodenal-jejunal bypass (GCP-DJB) and the commonly used sleeve gastrectomy (SG) in rats with type 2 diabetes mellitus (T2DM). METHODS: The rats were randomly divided into three groups: Control group (n = 6), SG group (n = 6), and GCP-DJB group (n = 6). Body weight, daily food intake, fasting blood glucose level, fasting insulin level, insulin resistance index, and fasting serum concentrations of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and bile acid were measured. In addition, postoperative changes in body weight and daily food intake at 2, 4, 6, 8, 10, and 12 weeks were also recorded. At week 12, an oral glucose tolerance test (OGTT) and insulin release test were performed to determine glucose tolerance. The insulin resistance index (IRI) was also measured. The postprandial secretion curves and area under the curve (AUC) of GLP-1, gastric inhibitory polypeptide (GIP), PYY, and bile acid were also calculated. RESULTS: Before surgery, no significant differences in body weight, daily food intake, fasting blood glucose, fasting insulin, insulin resistance index, fasting GLP-1, PYY, and bile acid were found among the three groups (P > 0.05). At postoperative week 12, body weight and food intake in the SG and GCP-DJB groups were lower than those in the Control group (P < 0.05), and body weight in the GCP-DJB group was lowest (P < 0.05). Glucose tolerance, postprandial serum insulin (INS), GLP-1, PYY, and bile acid were significantly higher in the SG and GCP-DJB groups than in the Control group (P < 0.05). The parameters related to glucose metabolism in the GCP-DJB group were higher than those in the SG group with the exception of serum insulin (P < 0.05). In addition, IRI and GIP secretion were significantly lower in the SG and GCP-DJB groups than in the Control group (P < 0.05) and were lowest in the GCP-DJB group (P < 0.05). CONCLUSION: Both GCP-DJB and SG are surgical options for the treatment of T2DM. The underlying mechanism of these treatments may be related to the decrease in body weight, food intake, GIP, IRI, and the increase in INS, GLP-1, PYY, and bile acid. According to the various metabolic indicators related to the hypoglycemic effects in T2DM, GCP-DJB was superior to SG.

Greater Curvature Plication with Duodenal-Jejunal Bypass: a Novel Metabolic Surgery for Type 2 Diabetes Mellitus.

OBJECTIVE: The study investigated the use of great curvature plication with duodenal-jejunal bypass (GCP-DJB) in a type 2 diabetic with obesity rat model. METHODS: Twenty-two Sprague-Dawley rats were given a high fat and sugar diet with subsequent intraperitoneal injection of a small dosage of streptozotocin (30 mg/kg) and randomly assigned to either GCP-DJB (n = 12) or Sham surgery (n = 10). Body weight, peripheral blood glucose, and fasting serum insulin were assayed, and insulin resistance index (IRI) was calculated, before and at 1, 2, 4, and 8 weeks after surgery. RESULTS: No differences were found in the preoperative characteristics of the two groups (P > 0.05). At week 1, the body weights decreased significantly, but there was no significant difference between the two groups (P > 0.05).The fasting blood glucose was significantly lower in the GCP-DJB than in the Sham group (P < 0.05), serum insulin levels were higher (P < 0.05), and IRI began to decline (P < 0.05). From 2 to 8 weeks, the body weight of Sham group gradually recovered and continued to rise, while the GCP-DJB group remained at a relatively lower state. Compared to the Sham group, the body weight, fasting blood glucose as well as IRI of GCP-DJB rats had significantly decreased (P < 0.05). But, the fasting insulin concentrations had significantly increased (P < 0.05). CONCLUSION: This novel GCP-DJB procedure established a stable animal model for the study of metabolic surgery to treat type 2 diabetes mellitus (T2DM).

Effects of Diet on Bile Acid Metabolism and Insulin Resistance in Type 2 Diabetic Rats after Roux-en-Y Gastric Bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is effective for the treatment of type 2 diabetes mellitus; however, the mechanism remains unclear. METHODS: The effects of RYGB on postprandial responses to three different diets (low carbohydrate (CH)-rich diet, high CH-rich diet, and fat-rich diet) of different nutritional composition in a Goto-Kakizaki (GK) diabetic rat model were assessed by measuring glucose tolerance, insulin resistance, incretin responses, and bile acid (BA) metabolism. RESULTS: GK-RYGB group rats lost weight and preferred low CH-rich diet, but there were no significant differences in BW among the different diets. Glucose tolerance and insulin resistance were improved in rats who underwent RYGB, together with higher levels of circulating BAs, plasma GLP-1, and PYY levels. GK-RYGB rats fed high CH-rich or fat-rich diet showed increased glucose level and insulin resistance, together with high plasma BA, GIP, and PYY levels compared to those fed a low CH-rich diet. CONCLUSION: RYGB improves glucose tolerance and insulin resistance which may be related to BA metabolism and hormone levels, and the nutrient composition of the diet affects the treatment effect of RYGB on T2DM.

A novel surgical strategy for secondary hyperparathyroidism: Purge parathyroidectomy.

OBJECTIVE: This study was intended to demonstrate the feasibility and efficacy of purge parathyroidectomy (PPTX) for patients with secondary hyperparathyroidism (SHPT). METHODS: The "seed, environment, and soil" medical hypothesis was first raised, following review of the literatures, to demonstrate the possible causes of persistence or recurrence of SHPT after parathyroidectomy. Subsequently, the novel surgical strategy of PPTX was proposed, which involves comprehensive resection of the fibro-fatty tissues, including visible or invisible parathyroid, within the region surrounded by the thyroid cartilage, bilateral carotid artery sheath, and the brachiocephalic artery. The perioperative information and clinical outcomes of patients who underwent PPTX from June 2016 to December 2016 were analyzed. RESULTS: In total, PPTX was performed safely in nine patients with SHPT from June 2016 to December 2016. The operative time for PPTX ranged from 95 to 135 min, and blood loss ranged from 20 to 40 mL. No patients with perioperative death, bleeding, convulsions, or recurrent laryngeal nerve injury were reported. The preoperative concentration of PTH ranged from 1062 to 2879 pg/mL, and from 12.35 to 72.69 pg/mL on the first day after surgery. In total, 37 parathyroid glands were resected. The postoperative pathologic examination showed that supernumerary or ectopic parathyroid tissues were found within the "non-parathyroid" tissues in three patients. No cases encountered persistence or recurrence of SHPT, or severe hypocalcemia during the follow-up period. CONCLUSION: PPTX involves comprehensive resection of supernumerary and ectopic parathyroid tissues, which may provide a more permanent means of reducing PTH levels.

To assess the effects of parathyroidectomy (TPTX versus TPTX+AT) for Secondary Hyperparathyroidism in chronic renal failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Secondary Hyperparathyroidism (SHPT) requiring parathyroidectomy (PTX) occurs more commonly in patients with progressive chronic kidney disease and in those on long-term lithium therapy. Successful PTX often results in a dramatic drop of parathyroid hormone level, relieves the patient from clinical symptoms, and reduces mortality. However, there is an ongoing debate on the optimal surgical treatment of SHPT. Currently, no clinical guidelines or trials have definitely answered the question of whether Total Parathyroidectomy (TPTX) is superior or equal to Total Parathyroidectomy with Autotransplantation (TPTX + AT). OBJECTIVE: The aims of the study were to compare the efficacy of two different surgical procedures and to develop evidence-based practice guidelines for the treatment of SHPT. METHODS: Citations were identified in the Medline, Cochrane, EMBASE, and Chinese Biomedical Literature databases through November 2016. The Newcastle-Ottawa Scale (NOS) score was used to assess the methodological quality of the studies included. All data were analyzed using Review Manager 5.3. RESULTS: A total of nine cohort studies and one Randomized Controlled Trials (RCT), comprising 1283 patients, were identified. The NOS score of all the studies included was 5 or above. Compared with TPTX + AT, patients in the TPTX group had lower rates of "recurrence" (OR = 0.20; 95%CI, 0.11-0.38; P < 0.01), "recurrence or persistence" (OR = 0.18; 95%CI, 0.10-0.33; P < 0.01), "reoperation due to recurrence or persistence" (OR = 0.17; 95%CI, 0.06-0.54; P = 0.002), and shorter "operative time" (WMD = -17.30; 95%CI, -30.53 to -4.06; P < 0.05), except for a higher risk of "hypoparathyroidism" (OR = 2.97; 95%CI, 1.09-8.08; P = 0.01). However, none of the patients had developed permanent hypocalcemia or adynamic bone disease. No significant difference was found for "symptomatic improvement", "complications", "drug requirements", and "hospital stay" (P > 0.05). CONCLUSION: The findings indicate that TPTX is superior to TPTX + AT, while referring to the rate of recurrent SHPT. However, this conclusion needs to be tested in large-scale confirmatory trials. TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of refractory SHPT.

Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism.

BACKGROUND: Excessive androgen exposure during pregnancy has been suggested to induce diabetic phenotypes in offspring in animal models. The aim of this study was to investigate whether pregestational maternal hyperandrogenism in human influenced the glucose metabolism in offspring via epigenetic memory from mother's oocyte to child's somatic cells. METHODS: Of 1782 reproductive-aged women detected pregestational serum androgen, 1406 were pregnant between 2005 and 2010. Of 1198 women who delivered, 1116 eligible mothers (147 with hyperandrogenism and 969 normal) were recruited. 1216 children (156 children born to mothers with hyperandrogenism and 1060 born to normal mother) were followed up their glycometabolism in mean age of 5years. Imprinting genes of oocyte from mothers and lymphocytes from children were examined. A pregestational hyperandrogenism rat model was also established. FINDINGS: Children born to women with hyperandrogenism showed increased serum fasting glucose and insulin levels, and were more prone to prediabetes (adjusted RR: 3.98 (95%CI 1.16-13.58)). Oocytes from women with hyperandrogenism showed increased insulin-like growth factor 2 (IGF2) expression. Lymphocytes from their children also showed increased IGF2 expression and decreased IGF2 methylation. Treatment of human oocytes with dihydrotestosterone upregulated IGF2 and downregulated DNMT3a levels. In rat, pregestational hyperandrogenism induced diabetic phenotypes and impaired insulin secretion in offspring. In consistent with the findings in human, hyperandrogenism also increased Igf2 expression and decreased DNMT3a in rat oocytes. Importantly, the same altered methylation signatures of Igf2 were identified in the offspring pancreatic islets. INTERPRETATION: Pregestational hyperandrogenism may predispose offspring to glucose metabolism disorder via epigenetic oocyte inheritance. Clinical trial registry no.: ChiCTR-OCC-14004537; www.chictr.org.

Application of carbon nanoparticles accelerates the rapid recovery of parathyroid function during thyroid carcinoma surgery with central lymph node dissection: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the efficacy of carbon nanoparticles in identifying lymph nodes and promoting parathyroid gland function recovery after thyroid carcinoma surgery along with central lymph node dissection. METHODS: A total of 231 patients who underwent thyroid carcinoma surgery combined with central lymph node dissection were divided into two groups: the CN group (intraoperative carbon nanoparticles injections) and the control group (no injection). Datas were collected respectively on the pre-operative, 1st, 7th and 30th postoperative days and monthly thereafter. While the pathological results (e.g. amount of incidental removed parathyroid glands and lymph nodes dissected), complications (e.g. rates of vocal cord paralysis, the neuromuscular symptoms, hypocalcemia and hypoparathyroidism), as well as follow-up outcomes of the serum Ca2+ and PTH levels were gathered and measured to be included in. RESULTS: In regard to the results of the pathological tests, the control group had a relatively higher incidence of incidental parathyroidectomy when compared to the CN group (P < 0.05). The mean number of central lymph nodes dissected was rather higher in the CN group than that of the control group (P < 0.05).With respect to the follow-up results, the CN group had an earlier and faster recovery of serum PTH levels as compared to the control group (P < 0.05). The serum PTH levels of the CN group were apparently higher than that of the control group at the first week and month postoperatively (P < 0.05). No significant differences were found in rates of long-term postoperative complications between the two groups (P > 0.05). CONCLUSION: Carbon nanoparticles play a key role in accurately identifying lymph nodes, reducing mistaken excision of parathyroid glands, accelerating rapid recovery of parathyroid function during thyroid carcinoma surgery with central lymph node dissection, without increasing the probability of postoperative complications.

Leptin down-regulates γ-ENaC expression: a novel mechanism involved in low endometrial receptivity.

OBJECTIVE: To examine epithelial Na(+) channel (ENaC) expression in endometrium of overweight/obese women with polycystic ovary syndrome (PCOS) during the window of implantation, and to explore the mechanism linking leptin-mediated reduction of γ-ENaC to low endometrial receptivity. DESIGN: Controlled, prospective, clinical, experimental study. SETTING: University-based infertility center. PATIENT(S): Blood and endometrium samples were collected from 12 control women and 12 overweight/obese PCOS patients. Pregnancy outcomes were obtained from 245 women with male-factor infertility (533 cycles) and 57 infertile women with PCOS (120 cycles) who underwent intrauterine insemination. INTERVENTION(S): Human endometrial biopsies. MAIN OUTCOME MEASURE(S): Expression of ENaC mRNA and protein in endometrium. RESULT(S): The expression of γ-ENaC decreased in the secretory phase endometrium of PCOS patients who showed increased serum leptin levels. In cultured endometrial cells (Ishikawa cells), leptin dose-dependently down-regulated the expression of γ-ENaC and reduced the JAr spheroid attachment rate, which could be blocked by knockdown of STAT3, a signal in the pathway of leptin receptor activation. The overweight/obese PCOS patients with increased serum leptin levels showed a significantly increased biochemical pregnancy rate, suggesting that high leptin might attenuate endometrial receptivity and increase very early pregnancy loss. CONCLUSION(S): High serum leptin may reduce endometrial receptivity by activating the STAT3 signal pathway and down-regulating γ-ENaC expression in the endometrium. These results provide valuable new insights into the molecular mechanisms linking abnormal ENaC gene expression to early pregnancy loss in overweight/obese PCOS patients.

The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis.

The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring.

Does the hepatic branch of vagus mediate the secretion of glucagon-like peptide-1 during the Roux-en-Y gastric bypass surgery?

OBJECTIVES: The purpose of this study is to investigate the impact of the hepatic branch of the vagus and Roux-en-Y gastric bypass (RYGB) on the level of fasting and postprandial serum glucagon-like peptide-1 (GLP-1) in type 2 diabetic mellitus rats. METHODS: Randomized block design, factorial experiment. Forty-five type 2 diabetic rats were divided into four groups: sham operation (S, n = 10) and sham operation with the hepatic branch of the vagotomy (SV, n = 11), Roux-en-Y gastric bypass (RYGB, n = 12) and RYGB without preservation of the vagus (RYGBV, n = 12). Levels of fasting and postprandial serum GLP-1 30 min after 50 % glucose solution (2 g/kg) by gavage were determined before surgery and postoperatively at 1, 4, and 8 weeks. Interactions between RYGB and the common hepatic branch were also assessed. RESULTS: Roux-en-Y gastric bypass surgery significantly increased the concentration of postprandial serum GLP-1 and maintained it at a higher level (P < 0.05). Preservation of vagus hepatic branch only increased the concentration of postprandial serum GLP-1 at the initial stage (P < 0.05), which gradually weakened over time (P > 0.05). Both RYGB and vagotomy of the hepatic branch had no influence on fasting serum GLP-1 (P > 0.05). CONCLUSIONS: During RYGB surgery for the long-term treatment of T2DM, preservation of the hepatic branch of the vagus might have no impact on serum GLP-1 level.

Cardiovascular dysfunction in offspring of ovarian-hyperstimulated women and effects of estradiol and progesterone: a retrospective cohort study and proteomics analysis.

CONTEXT: The cardiovascular dysfunction in children born with assisted reproductive technologies has been of great concern. However, the association of ovarian hyperstimulation syndrome (OHSS), a complication of assisted reproductive technologies, with worse cardiovascular functions and underlying mechanism remains unknown. OBJECTIVES: The objective of the study was to assess the cardiovascular functions of children born to mothers with OHSS and investigate the underlying regulator(s). DESIGN AND SETTING: This was a retrospective cohort recruited in a university hospital. PARTICIPANTS AND METHODS: We assessed the cardiovascular functions by Doppler echography in 42 children born to OHSS women, 34 children of mothers with non-OHSS in vitro fertilization, and 48 spontaneously conceived (SC) children (mean age ∼ 4.5 y). Groups were matched for gestational age at delivery and birth weight. An isobaric tag for relative and absolute quantitation-labeled proteomics analysis was performed with another set of umbilical arteries from OHSS and SC pregnancies (n = 3 for both groups). RESULTS: Children of OHSS mothers showed a significantly decreased mitral ratio of early to late mitral peak velocities, reduced systolic and diastolic diameters of common carotid arteries, and impaired flow-mediated dilation compared with non-OHSS in vitro fertilization and SC children. Intima-media thickness and arterial stiffness indices were similar in the three groups. In the proteomics study, 1640 proteins were identified from OHSS and SC umbilical arteries, and 40 differentially expressed proteins were selected for further analysis. Estradiol and progesterone were identified as activated upstream regulators. CONCLUSIONS: Children born to ovarian-hyperstimulated women displayed cardiovascular dysfunctions. The underlying mechanisms may involve the effects of supraphysiological estradiol and progesterone levels.