Maternal Obesity Influences Placental Nutrient Transport, Inflammatory Status, and Morphology in Human Term Placenta.

CONTEXT: Maternal obesity has a significant impact on placental development. However, this impact on the placenta's structure and function (ie, nutrient transport and hormone and cytokine production) is a controversial subject. OBJECTIVE: We hypothesized that maternal obesity is associated with morphologic, secretory, and nutrient-related changes and elevated levels of inflammation in the placenta. DESIGN: We collected samples of placental tissue from 2 well-defined groups of pregnant women from 2017 to 2019. We compared the 2 groups regarding placental cytokine and hormone secretion, immune cell content, morphology, and placental nutrient transporter expressions. SETTING: Placenta were collected after caesarean section performed by experienced clinicians at Centre Hospitalier Intercommunal (CHI) of Poissy-Saint-Germain-en-Laye. PATIENTS: The main inclusion criteria were an age between 27 and 37 years old, no complications of pregnancy, and a first-trimester body mass index of 18-25 kg/m2 for the nonobese (control) group and 30-40 kg/m2 for the obese group. RESULTS: In contrast to our starting hypothesis, we observed that maternal obesity was associated with (1) lower placental IL-6 expression and macrophage/leukocyte infiltration, (2) lower placental expression of GLUT1 and SNAT1-2, (3) a lower placental vessel density, and (4) lower levels of placental leptin and human chorionic gonadotropin production. CONCLUSION: These results suggest that the placenta is a plastic organ and could optimize fetal growth. A better understanding of placental adaptation is required because these changes may partly determine the fetal outcome in cases of maternal obesity.

Maternal obesity influences expression and DNA methylation of the adiponectin and leptin systems in human third-trimester placenta.

BACKGROUND: It is well established that obesity is associated with dysregulation of the ratio between the two major adipokines leptin and adiponectin. Furthermore, it was recently reported that maternal obesity has a significant impact on placental development. Leptin and adiponectin are present at the fetal-maternal interface and are involved in the development of a functional placenta. However, less is known about leptin and adiponectin's involvement in the placental alterations described in obese women. Hence, the objective of the present study was to characterize the placental expression and DNA methylation of these two adipokine systems (ligands and receptors) in obese women. RESULTS: Biopsies were collected from the fetal and maternal sides of third-trimester placenta in obese and non-obese (control) women. In both groups, leptin levels were higher on the fetal side than the maternal side, suggesting that this cytokine has a pivotal role in fetal growth. Secondly, maternal obesity (in the absence of gestational diabetes) was associated with (i) elevated DNA methylation of the leptin promoter on fetal side only, (ii) hypomethylation of the adiponectin promoter on the maternal side only, (iii) significantly low levels of leptin receptor protein (albeit in the absence of differences in mRNA levels and promoter DNA methylation), (iv) significantly low levels of adiponectin receptor 1 mRNA expression on the maternal side only, and (v) elevated DNA methylation of the adiponectin receptor 2 promoter on the maternal side only. CONCLUSION: Our present results showed that maternal obesity is associated with the downregulation of both leptin/adiponectin systems in term placenta, and thus a loss of the beneficial effects of these two adipokines on placental development. Maternal obesity was also associated with epigenetic changes in leptin and adiponectin systems; this highlighted the molecular mechanisms involved in the placenta's adaptation to a harmful maternal environment.

Identification by proteomics of oviductal sperm-interacting proteins.

The interactions between oviductal fluid (OF) proteins and spermatozoa play major roles in sperm selection, storage and capacitation before fertilization. However, only a few sperm-interacting proteins in the OF has been identified and very little is known about the regulation of sperm-oviduct interactions across the estrous cycle. Samples of bovine frozen-thawed sperm from three bulls were incubated with OF at pre-, post-ovulatory stages (Pre-/Post-ov) or luteal phase (LP) of the estrous cycle (7 mg/mL proteins, treated groups) or with a protein-free media (control). The proteomes of sperm cells were assessed by nanoLC-MS/MS and quantified by label-free methods. A total of 27 sperm-interacting proteins originating in the OF were identified. Among those, 14 were detected at all stages, eight at Post-ov and LP and five only at LP. The sperm-interacting proteins detected at all stages or at LP and Post-ov were on average more abundant at LP than at other stages (P < 0.05). At Pre-ov, OVGP1 was the most abundant sperm-interacting protein while at Post-ov, ACTB, HSP27, MYH9, MYH14 and OVGP1 were predominant. Different patterns of abundance of sperm-interacting proteins related to the stage were evidenced, which greatly differed from those previously reported in the bovine OF. In conclusion, this study highlights the important regulations of sperm-oviduct interactions across the estrous cycle and provides new protein candidates that may modulate sperm functions.

Prevention of deoxynivalenol- and zearalenone-associated oxidative stress does not restore MA-10 Leydig cell functions.

The worldwide contamination of grains designated to human and animal feeding with Fusarium mycotoxins is a significant problem. Among Fusarium mycotoxins, deoxynivalenol (DON) and zearalenone (ZEA) are the most prevalent mycotoxins found in cereals. Co-occurrence of DON and ZEA is also very frequent and indicates that these mycotoxins might be involved in a wide range of synergistic or additive interactions. Both mycotoxins have been linked to various male reproduction problems including downregulation of steroidogenesis. In this study, the impact of DON and ZEA alone or in combination on the viability and steroid production of Leydig cell line MA-10 was determined. The ability of vitamin E, sesamin and their combination to prevent oxidative stress and restore progesterone secretion in DON- and ZEA-exposed cells was also determined. Results showed that MA-10 cells were more sensitive to the effect of DON compared to ZEA. DON and ZEA also significantly reduced MA-10 progesterone secretion after forskolin activation but no significant interactions between DON and ZEA were detected. Preventive treatment with the combination of vitamin E and sesamin significantly reduced ROS production and increased cell survival after exposition to DON and ZEA. However this treatment failed to restore normal progesterone secretion. In conclusion, both DON and ZEA are deleterious to steroidogenesis in Leydig cells. Prevention of oxidative stress caused by DON and ZEA was effective to restore cell viability but failed to restore other functions of Leydig cells suggesting that ROS production is not the main cause of steroidogenic failure in DON and ZEA treated MA-10 cells.