Labor inhibits placental mechanistic target of rapamycin complex 1 signaling.

INTRODUCTION: Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. METHODS: Placental tissue was collected from healthy, term pregnancies (n = 15 no-labor; n = 12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFĸB p65 and PPARγ DNA binding activity was measured in isolated nuclei. RESULTS: Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFĸB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. DISCUSSION AND CONCLUSION: Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor.

Expression and localization of the omega-3 fatty acid receptor GPR120 in human term placenta.

Fatty acids can function as signaling molecules, acting through receptors in the cytosol or on the cell surface. G-Protein Receptor (GPR)120 is a membrane-bound receptor mediating anti-inflammatory and insulin-sensitizing effects of the omega-3 fatty acid docohexaenoic acid (DHA). GPR120 dysfunction is associated with obesity in humans. Cellular localization of GPR120 and the influence of maternal obesity on GPR120 protein expression in the placenta are unknown. Herein we demonstrate that GPR120 is predominantly expressed in the microvillous membrane (MVM) of human placenta and that the expression level of this receptor in MVM is not altered by maternal body mass index (BMI).

IFPA Meeting 2013 Workshop Report I: diabetes in pregnancy, maternal dyslipidemia in pregnancy, oxygen in placental development, stem cells and pregnancy pathology.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2013 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) diabetes in pregnancy; 2) lipids, fatty acids and the placenta; 3) oxygen in placental development and pathologies; 4) stem cells and pathologies.

Placental transport in response to altered maternal nutrition.

The mechanisms linking maternal nutrition to fetal growth and programming of adult disease remain to be fully established. We review data on changes in placental transport in response to altered maternal nutrition, including compromized utero-placental blood flow. In human intrauterine growth restriction and in most animal models involving maternal undernutrition or restricted placental blood flow, the activity of placental transporters, in particular for amino acids, is decreased in late pregnancy. The effect of maternal overnutrition on placental transport remains largely unexplored. However, some, but not all, studies in women with diabetes giving birth to large babies indicate an upregulation of placental transporters for amino acids, glucose and fatty acids. These data support the concept that the placenta responds to maternal nutritional cues by altering placental function to match fetal growth to the ability of the maternal supply line to allocate resources to the fetus. On the other hand, some findings in humans and mice suggest that placental transporters are regulated in response to fetal demand signals. These observations are consistent with the idea that fetal signals regulate placental function to compensate for changes in nutrient availability. We propose that the placenta integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensors. Together, these signals regulate placental growth and nutrient transport to balance fetal demand with the ability of the mother to support pregnancy. Thus, the placenta plays a critical role in modulating maternal-fetal resource allocation, thereby affecting fetal growth and the long-term health of the offspring.

IFPA Meeting 2011 workshop report I: Placenta: Predicting future health; roles of lipids in the growth and development of feto-placental unit; placental nutrient sensing; placental research to solve clinical problems--a translational approach.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, four of which are summarized in this report. These workshops related to both basic science and clinical research into placental growth and nutrient sensing and were divided into 1) placenta: predicting future health; 2) roles of lipids in the growth and development of feto-placental unit; 3) placental nutrient sensing; 4) placental research to solve clinical problems: a translational approach.

Effect of IL-6 and TNF-α on fatty acid uptake in cultured human primary trophoblast cells.

Maternal obesity and gestational diabetes (GDM) are conditions associated with fetal overgrowth and excessive fat accumulation in the fetus, implicating an increased placental nutrient transfer in these pregnancies. Obese and GDM mothers have altered metabolism and hormone levels, including elevation of maternal circulatory lipids and pro-inflammatory cytokines. We tested the hypothesis that interleukin (IL)-6 and tumor necrosis factor (TNF)-α stimulate placental fatty acid transport, as these pro-inflammatory cytokines have been shown to affect lipid metabolism in other tissues. In cultured primary human trophoblast cells IL-6, but not TNF-α, stimulated fatty acid accumulation, as measured by BODIPY fluorescence. The increased fatty acid accumulation could not be explained by an increased expression of key components in placental fatty acid transport, such as adipophilin, fatty acid transport protein (FATP)1, FATP4, or lipoprotein lipase. In a cohort of lean and overweight/obese pregnant women, increasing maternal third trimester IL-6 plasma concentrations correlated with decreasing placental lipoprotein lipase activity. However, as no effect on lipoprotein lipase activity was observed in cultured trophoblast cells after exposure to either IL-6 or TNF-α, the correlation between maternal circulatory IL-6 levels and placental lipoprotein lipase activity at term is unlikely to represent a cause-and-effect relationship. In conclusion, high levels of IL-6 stimulate trophoblast fatty acid accumulation, which could contribute to an excessive nutrient transfer in conditions associated with elevated maternal IL-6 such as obesity and gestational diabetes.

Professional roller hockey injuries.

OBJECTIVE: To study the incidence and types of injuries sustained by professional roller hockey players in practices and games, and to compare these statistics with those from ice hockey. DESIGN: This injury survey used a strict definition of injury, standardized reporting strategies, and diagnosis by a team physician as standards by which to analyze the characteristics of roller hockey injuries. SETTING: The injuries were recorded after the players had been examined by a team physician at the game or practice site or in the physician's office. PARTICIPANTS: During three seasons for one roller hockey team and one season for another team, an average of 22 players per team participated in the study. Due to personnel changes, the team rosters were modified between seasons. Each player injury was included in the study. An injury was defined as any physical impairment caused during a practice or game that eliminated the player from that practice or game or the next day's practice session or contest, or any physical ailment that necessitated a physical examination by the team physicians. MAIN OUTCOME MEASURE: Injury data were categorized and injury rates were calculated. RESULTS: 122 injuries were recorded during four professional roller hockey seasons, resulting in an overall participation injury rate of 14.4 per 1,000 player hours. The game injury rate was 304.9 per 1,000 player hours. The players were 105.1 times more likely to be injured during a game than during practice. Preseason practices produced 4.5 times more injuries than regular season practices. In comparison, sample data from the only other published study of roller hockey injuries and from several studies of ice hockey have indicated game injury rates of 139.0 (roller hockey), 119.0, 96.1, 78.4, 78.8, and 66.0 per 1,000 player hours, respectively. CONCLUSION: Results of this study demonstrate that roller hockey produces a higher rate of both contact and noncontact injuries than ice hockey; this contradicts the findings of the only other published research study on injuries in roller versus ice hockey. This increased incidence of injury may be due in part to the differences in surfaces, and can prove hazardous to even the recreational roller hockey player or in-line skater.

Hormonal effects of the 300 microgram norethisterone (NET) minipill. 3. Comparison of the short-term (2nd month) and medium-term (6th month) effects in 21 subjects.

PIP: Levels of immunoreactive follitropin (FSH), lutropin (LH), estradiol, progesterone, 17-hydroxyprogesterone and 20 alpha-dihydroprogesterone were analyzed in peripheral plasma samples collected daily from 21 normally menstruating women during a pretreatment (control) cycle and during months 2 and 6 of administration of the 300 ug norethisterone (NET) minipill. In the untreated cycles studied, a satisfactory agreement was found between the levels of 20 alpha-dihydroprogesterone and progesterone, whereas the 17-hydroxyprogesterone levels were correlated to those of estradiol. In most of the 42 treatment cycles a satisfactory agreement was found between the assessments based on progesterone levels, and on those of 20 alpha-dihydroprogesterone and 17-hydroxyprogesterone. In the majority of cycles with little or no luteal activity, the profile of 17-hydroxyprogesterone levels appeared to follow that of estradiol. The levels of FSH and LH in 13 subjects in whom the administration of NET suppressed luteal function did not differ from those found in 8 subjects exhibiting normal, ovulatory-like steroid profiles during the minipill administration. Futhermore, in the majority of the treatment cycles in the latter group, the gonadotrophin profiles were bizarre and appeared to be unrelated to the characteristic changes in steroid profiles which sometimes occurred in the virtual absence of any midcycle rise in FSH and LH levels. The 17-hydroxyprogesterone levels of the control cycles were closely related to the nature of the subsequent ovarian reaction to the minipill; in women exhibiting an ovulatory-type steroid response to the subsequent administration of the NET minipill, the pretreatment levels of 17-hydroxyprogesterone were significantly higher than in women in whom this treatment resulted in a complete or incomplete suppression of luteal activity.^ieng