Eve Mourier

In Vivo Evaluation of Cervical Stiffness Evolution during Induced Ripening Using Shear Wave Elastography, Histology and 2 Photon Excitation Microscopy: Insight from an Animal Model.

Prematurity affects 11% of the births and is the main cause of infant mortality. On the opposite case, the failure of induction of parturition in the case of delayed spontaneous birth is associated with fetal suffering. Both conditions are associated with precocious and/or delayed cervical ripening. Quantitative and objective information about the temporal evolution of the cervical ripening may provide a complementary method to identify cases at risk of preterm delivery and to assess the likelihood of successful induction of labour. In this study, the cervical stiffness was measured in vivo in pregnant sheep by using Shear Wave Elastography (SWE). This technique assesses the stiffness of tissue through the measurement of shear waves speed (SWS). In the present study, 9 pregnant ewes were used. Cervical ripening was induced at 127 days of pregnancy (term: 145 days) by dexamethasone injection in 5 animals, while 4 animals were used as control. Elastographic images of the cervix were obtained by two independent operators every 4 hours during 24 hours after injection to monitor the cervical maturation induced by the dexamethasone. Based on the measurements of SWS during vaginal ultrasound examination, the stiffness in the second ring of the cervix was quantified over a circular region of interest of 5 mm diameter. SWS was found to decrease significantly in the first 4–8 hours after dexamethasone compared to controls, which was associated with cervical ripening induced by dexamethasone (from 1.779 m/s ± 0.548 m/s, p < 0.0005, to 1.291 m/s ± 0.516 m/s, p < 0.000). Consequently a drop in the cervical elasticity was quantified too (from 9.5 kPa ± 0.9 kPa, p < 0.0005, to 5.0 kPa ± 0.8 kPa, p < 0.000). Moreover, SWE measurements were highly reproducible between both operators at all times. Cervical ripening induced by dexamethasone was confirmed by the significant increase in maternal plasma Prostaglandin E2 (PGE2), as evidenced by the assay of its metabolite PGEM. Histological analyses and two-photon excitation microscopy, combining both Second Harmonic Generation (SHG) and Two-photon Fluorescence microscopy (2PF) contrasts, were used to investigate, at the microscopic scale, the structure of cervical tissue. Results show that both collagen and 2PF-active fibrillar structures could be closely related to the mechanical properties of cervical tissue that are perceptible in elastography. In conclusion, SWE may be a valuable method to objectively quantify the cervical stiffness and as a complementary diagnostic tool for preterm birth and for labour induction success.

Sex and breed-dependent organ development and metabolic responses in foetuses from lean and obese/leptin resistant swine.

The present study aimed to determine the effects of breed and sex on growth patterns and metabolic features of advanced-pregnancy foetuses exposed to the same environmental conditions. Thus, at Day 62 of pregnancy, swine foetuses from an obese breed with leptin resistance (Iberian breed) were compared to lean crossbred foetuses (25% Large White ×25% Landrace ×50% Pietrain). There were differential developmental patterns in foetuses with leptin resistance, mainly a higher relative weight of the brain resembling “brain-sparing effect”. Prioritization of brain growth may be protective for the adequate growth and postnatal survival of the Iberian individuals, an ancient breed reared in extensive semi-feral conditions for centuries. There were also clear sex-related differences in foetal development and metabolism in the Iberian breed. Female Iberian foetuses were similar in size and weight to male littermates but had a significantly higher relative liver to body weight ratio resembling “liver-sparing effect” and a trend for a higher relative intestine to body ratio. Moreover, the availability of triglycerides, cholesterol and IL-6 in female Iberian foetuses was similar to that of lean crossbred foetuses. Overall, these features may favour a better postnatal survival and development of females, the sex more critical for the species survival. These findings set the basis for future translational studies aimed at increasing the knowledge on the interaction between genetic and environmental factors in the early programming of the adult phenotype.

Effects of a preconceptional and gestational multi-vitamin-mineral-omega3 supplementation on fetoplacental development in a rabbit model

The developmental origins ofhealth and disease concept stipulates that nutritional imbalance in the preconceptional and gestational periods induces risks for the development and long-term health of the individual. In industrialized countries, most women take nutritional supplements before and during pregnancy, regardless of their diet. Potentially harmful embtyonic and fetal effects of an excess multi-micronutrient supplementation, however, are not known. The objective of this study was to assess, using a rabbit mode!, the effects of a multi-vitamin-mineral-mnega 3 supplementation (Gestarelle® G) administered in slight excess during preconceptional and gestational periods. Twenty-seven New Zealand does were used. Supplementation contained vitamins (Bl, B2, BS, B6, B8, B9, B12, C, E), minerais (magnesium, iron, copper, iodine), and n-3 polyunsaturated fatty acids (n-3 PUFA; namely DHA and EPA) in the form of oral capsules administered daily from 10 days before mating until the end ofpregnancy. Group lX posology allometrically matched thatltsedinhumans (n = 10), representing an excess of6 to 50% ofrabbit needs. Group 3X rabbits received 3 times the recommended posology (n = 9; 18 to 150% ofrabbit needs), whereas the control group received capsules containing only excipient (n = 8). Embryo and fetoplacental developmentwas monitored bytransabdominal two- and three-dimensional ultrasound and Doppler on Days 5, 7, 14, 21, and 28 with 5 conceptuses perdoe examined each time. Does were killed on Day 28 (term = 31 days), 24 h after the last capsule administration. Maternai and fetal blood, as weil as placenta and fetal organs, were collected. Data were analysed by ANOVA and Kruskall-Wallis as appropriatc. The n-3 PUFA plasma concentrations increased in the 3X does (P < 0.01). Fetal plasma concentrations were increased ont y in males in the lX group (P < 0.001) and bath in females and males in the 3X group (P < le- 15 . No statistical differences wcre observed between treatments for any of the ultrasound or Doppler analyses. In total, 208 fetuses were collected with no difference in litter size, sex ratio, nor biometrie measurements between groups. No structural anomaly was observed by histological analysis of fetal organs. In conclusion, multi-vitamin mineral-omega 3 supplementation administered dming the preconceptional and gestational periods in a rabbit mode! in the present study and within the measured parameters had no deleterious effect for dam and conceptuses at 1 and 3 times the recommended posology. Further worlc is on-going to study the effects on fetal brain development. Further studies are needed to evaluate putative post-natal effects.