[Obstetrical outcome of renal transplant patients followed in a type III maternity hospital. Retrospective study from 2000 to 2020]. / Devenir obstétrical des patientes transplantées rénales suivies dans une maternité de type III. Étude rétrospective de 2000 à 2020.

AIM: To describe pregnancy outcome of kidney transplant patients till 1 year postpartum. METHODS: This retrospective, monocentric study included 15 kidney transplant patients who presented 18 pregnancies, between January 2000 and January 2020. For each of them, we searched for possible obstetrical, fetal and renal complications and we evaluated renal function before, during and after pregnancy. RESULTS: The live birth rate was 84% (16/19) with an average gestational age at delivery of 37 weeks of gestation. The rate of prematurity was 50% (8/16), gestational diabetes was 16.6% (3/18) and preeclampsia was 27.7% (5/18). Cesarean section was performed in 61.1% (11/18) of cases including, 81.8% (9/11) unplanned surgery. The average birth weight was 2635 grams and 37.5% (6/16) of the newborn were small for gestational age. All patients had stable renal function before conception of pregnancy. We noticed two acute graft rejection during pregnancy with only one resulting in graft loss. Four patients had a reduced graft function in 12months of the postpartum. CONCLUSION: Risk of maternal, fetal and renal complications remained high in kidney transplant recipients. Pregnancy should be carefully planned in transplanted women associated with adequate follow-up according to clinical guidelines (normal renal function and blood pressure without proteinuria before pregnancy, no recent graft rejection, period of one year after transplant respected and no teratogenic treatment in the month before pregnancy).

Benefits of Premaquick® Combined Detection of IL-6/Total IGFBP-1/Native IGFBP-1 to Predict Preterm Delivery.

We conducted a prospective double-blind study to compare two vaginal diagnostic methods in singleton pregnancies with threatened preterm labor (TPL) at the University Hospital of Clermont-Ferrand (France) from August 2018 to December 2020. Our main objective was to compare the diagnostic capacity at admission, in terms of positive predictive value (PPV) and negative predictive value (NPV), of Premaquick® (combined detection of IL-6/total IGFBP-1/native IGFBP-1) and QuikCheck fFN™ (fetal fibronectin) for delivery within 7 days in cases of TPL. We included 193 patients. Premaquick® had a sensitivity close to 89%, equivalent to QuikCheck fFN™, but a higher statistical specificity of 49.5% against 38.6% for QuikCheck fFN™. We found no superiority of Premaquick® over QuickCheck fFN™ in terms of PPV (6.6% vs. 7.9%), with NPV being equivalent in predicting childbirth within 7 days in cases of TPL (98.6% vs. 98.9%). Nevertheless, the combination of positive native and total IGFBP-1 and the combination of all three positive markers were associated with a higher PPV. Our results, though non-significant, support this combined multiple-biomarker approach to improve testing in terms of predictive values.

[Evolution of the obstetrical Shock Index in postpartum haemorrhage according to the use of sulprostone]. / Évolution du Shock Index obstétrical lors d'une hémorragie du post-partum selon le recours à la sulprostone.

OBJECTIVES: The Shock Index (SI) is used in emergency medicine to assess the severity of active bleeding and in the postpartum context for postpartum haemorrhage (PPH). We investigated the diagnostic value of haemodynamic parameters (SI, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)) in predicting subsequent use of uterotonic sulprostone treatment. METHODS: This was a retrospective study including parturients with PPH ≥ 500mL between January 2017 and December 2018. Hemodynamic parameters at the diagnosis of PPH were compared according to whether the patient required subsequent sulprostone treatment (sulprostone(+) group) or not (sulprostone(-) group). RESULTS: We included in the analysis 147 patients. The SI was significantly higher in the sulprostone(+) group (0.92±0.28 vs. 0.83±0.22; p=0.04). The SBP (107.2±17.5 vs. 113.8±17.7mmHg; p=0.03), DBP (56.8±12,2 vs. 61.5±13,2mmHg; p=0.04), MAP (73.6±12.6 vs. 78.5±13.4mmHg; p=0.03) were significantly lower in the same group. No difference between AUC of these parameters to predict the use of sulprostone was found (AUC between 0.59 and 0.61). No significant difference was found for the HR between the two groups. CONCLUSION: The diagnostic value of SI appeared to be low and similar to other haemodynamic parameters in predicting the use of sulprostone.

Risk Factors for Perineal Wound Breakdown in Early Postpartum: A Retrospective Case-Control Study.

We conducted a retrospective case-control study in patients presenting a perineal tear (second degree or higher) or episiotomy complicated by wound breakdown during maternity stay to identify risk factors associated with wound breakdown in early postpartum with a view to improving the quality of care. We collected ante- and intrapartum characteristics and outcomes at the postpartum visit. In all, 84 cases and 249 control subjects were included. In univariate analysis, primiparity, absence of history of vaginal delivery, a longer second phase of labour, instrumental delivery, and a higher degree of laceration emerged as risk factors for early perineal suture breakdown postpartum. Gestational diabetes, peripartum fever, streptococcus B, and suture technique did not emerge as risk factors for perineal breakdown. Multivariate analysis confirmed that instrumental delivery (OR = 2.18 [1.07; 4.41], p = 0.03) and a longer second phase of labour (OR = 1.72 [1.23; 2.42], p = 0.001) were risk factors for early perineal suture breakdown.

Factors of Non-Compliance with a Protocol for Oral Administration of Misoprostol (Angusta®) 25 Micrograms to Induce Labor: An Observational Study.

We set out to identify factors of non-compliance with a protocol for the oral administration of misoprostol 25 µg (Angusta®) every 2 h (up to eight tablets), for the induction of labor (IOL). We conducted a retrospective study on IOL at term, on singleton pregnancies from 2019 to 2021, in a university hospital. The study included 195 patients, comprising 144 compliant protocols. Pain was statistically more frequent in the non-compliance group (92.2% vs. 62.5%, p < 0.001), and when a midwife was unavailable (15.7% vs. 0.7%, p < 0.001). A multivariable analysis found factors of good response (defined as going into labor before the administration of the median number of tablets, i.e., six) to be an indication for PROM (OR: 12.03, 95% CI: 5.42-26.71), and gestational age at induction (OR: 1.54, 95% CI: 1.19-2.01), independently of BMI, initial Bishop score, and parity. Patients with pain who were able to follow the protocol delivered 9 h earlier than patients with pain who interrupted the protocol and 16 h earlier than patients who experienced no pain. We identified two key elements that favored compliance: (i) providing the next tablet in advance; and (ii) offering patients early epidural analgesia when in pain in order to continue the protocol and go into labor promptly.

Blood Biomarkers for Return to Play after Concussion in Professional Rugby Players.

We prospectively evaluated a panel of seven blood biomarkers (S100 calcium-binding protein B [S100B], neuron specific enolase [NSE], spectrin breakdown products [SBDP], ubiquitin C-terminal hydrolase L1 [UCHL1], glial fibrillary acidic protein [GFAP], neurofilament light chain [NFL], and tubulin-associated unit [Tau]) for sport-related concussion (SRC) in a large multi-centric cohort of 496 professional rugby players from 14 French elite teams. Players were sampled twice during the season (beginning and end) away from any sport practice. From these two baseline samples, we evaluated the intra-individual variability to establish the effect of rugby on blood biomarkers over a season. Only S100B and GFAP remained stable over the course of a season. During the period of the study, a total of 45 SRC cases was reported for 42 players. In 45 SRCs, the head injury assessment (HIA) process was performed and blood collection was realized 36 h after the concussion (HIA-3 stage). For each biomarker, raw concentrations measured 36 h after SRC were not significantly different between players with a non-resolutive SRC (n = 28) and those with a resolutive SRC (n = 17; p between 0.06 and 0.92). In a second step, blood concentrations measured 36 h after SRC were expressed according to the basal concentrations as an individual percentage change (PCH36[%]), calculated as follows: PCH36 = 100 × (([Biomarker]36h - [Biomarker]basal)/[Biomarker]basal). S100B and NFL concentrations expressed as PCH36[%] were significantly different between non-resolutive and resolutive SRCs (p = 0.006 and 0.01 respectively), with a positive delta found in non-resolutive SRCs. Among the two biomarkers, it is important to note that only the S100B protein was stable during the season. In the context of our study, during HIA-3 assessment, S100B seems to perform better than NSE, SBDP, UCHL1, GFAP, NFL, and Tau as biomarker for SRC. From a clinical standpoint, the S100B modification over baseline may be valuable, at 36 h after concussion to distinguish non-resolutive SRC from resolutive SRC.

Cross-Cultural Adaptation and Psychometric Properties of the French Version of the EXIT to Measure Women's Experiences of Induction of Labor.

BACKGROUND: In France, more than 20% of women require induction of labor (IOL), which can be psychologically and emotionally challenging for patients. It is important to assess how they feel about their IOL experiences. Our aim was to cross-culturally adapt and evaluate the psychometric properties of a French version of the EXIT to assess women's experiences of IOL. METHODS: The EXIT was cross-culturally adapted by conducting forward and backward translations following international guidelines. A cross-sectional study was conducted to assess the psychometric properties of the ten French EXIT items: data completeness, factor analysis, internal consistency, score distribution, floor and ceiling effects, inter-subscale correlations, convergent validity, and test-retest reliability. RESULTS: The EXIT was successfully cross-culturally adapted to the French context and any IOL method. The results obtained from 163 patients requiring IOL showed good acceptability. Exploratory factor analysis resulted in a three-factor solution with subscales reflecting the experiential aspects of time taken to give birth, discomfort with IOL, and subsequent contractions. Good internal consistency (Cronbach's alpha or Spearman correlation coefficients ranging from 0.55 to 0.84) and good test-retest reliability (intraclass correlation coefficients ranging from 0.66 to 0.85) for the three identified subscales were found. CONCLUSIONS: The ten-item French EXIT is a valid and reliable instrument for the self-assessment of women's experiences of IOL in the three weeks following delivery for any method of IOL used. As a patient-reported outcome measure, it would allow the comparison of experiential outcomes across IOL studies in order to include women's preferences in decisions regarding their care.

Double Balloon Catheter (Plus Oxytocin) versus Dinoprostone Vaginal Insert for Term Rupture of Membranes: A Randomized Controlled Trial (RUBAPRO).

Background: The aim of this study is to demonstrate that a double balloon catheter combined with oxytocin decreases time between induction of labor and delivery (TID) as compared to a vaginal dinoprostone insert in cases of premature rupture of membranes at term. Methods: This is a prospective, randomized, controlled trial including patient undergoing labor induction for PROM at term with an unfavorable cervix in Clermont-Ferrand university hospital. We compared the double balloon catheter over a period of 12 h with adjunction of oxytocin 6 h after catheter insertion versus dinoprostone vaginal insert. After device ablation, cervical ripening continued only with oxytocin. The main outcome was TID. Secondary outcomes concerned delivery mode, as well as maternal and fetal outcome, and were adjusted for parity. Results: 40 patients per group were randomized. Each group had similar baseline characteristics. The study failed to demonstrate reduced TID (16.2 versus 20.2 h, ES = 0.16 (−0.27 to 0.60), p = 0.12) in the catheter group versus dinoprostone except in nulliparous women (17.0 versus 26.5 h, ES = 0.62 (0.10 to 1.14), p = 0.006). The rate of vaginal delivery <24 h significantly increased with combined induction (88.5% versus 66.6%, p = 0.03). No statistical difference was observed concerning caesarean rate (12.5% versus 17.5%, p > 0.05), chorioamnionitis (0% versus 2.5%, p = 1), postpartum endometritis, or maternal or neonatal outcomes. Procedure-related pain and tolerance to devices were found to be similar for the two methods. Interpretation: The double balloon catheter combined with oxytocin is an alternative for cervical ripening in case of PROM at term, and may reduce TID in nulliparous women.

Physiological TLR4 regulation in human fetal membranes as an explicative mechanism of a pathological preterm case.

The integrity of human fetal membranes is crucial for harmonious fetal development throughout pregnancy. Their premature rupture is often the consequence of a physiological phenomenon that has been exacerbated. Beyond all the implied biological processes, inflammation is of primary importance and is qualified as 'sterile' at the end of pregnancy. In this study, complementary methylomic and transcriptomic strategies on amnion and choriodecidua explants obtained from the altered (cervix zone) and intact fetal membranes at term and before labour were used. By cross-analysing genome-wide studies strengthened by in vitro experiments, we deciphered how the expression of toll-like receptor 4 (TLR4), an actor in pathological fetal membrane rupture, is controlled. Indeed, it is differentially regulated in the altered zone and between both layers by a dual mechanism: (1) the methylation of TLR4 and miRNA promoters and (2) targeting by miRNA (let-7a-2 and miR-125b-1) acting on the 3'-UTR of TLR4. Consequently, this study demonstrates that fine regulation of TLR4 is required for sterile inflammation establishment at the end of pregnancy and that it may be dysregulated in the pathological premature rupture of membranes.

Predictors of Short Latency Period Exceeding 48 h after Preterm Premature Rupture of Membranes.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is a complication responsible for a third of preterm births. Clinical management is initially hospital based, but homecare management is possible if patients are clinically stable 48 h after PPROM. This study set out to determine factors that are predictive of short latency (delivery ≤ 7 days) exceeding 48 h after PPROM, enabling estimation of the prevalence of maternal and neonatal complications and comparison of maternal and fetal outcomes between inpatient and outpatient management. METHOD: This was a monocentric retrospective study conducted between 1 January 2010 and 28 February 2017 on all patients experiencing PPROM at 24 to 34 weeks + 6 days and who gave birth after 48 h. Maternal, obstetric, fetal, and neonatal variables were included in the data collected. The primary endpoint was latency, defined as the number of days between rupture of membranes and delivery. RESULTS: 170 consecutive patients were analyzed. Short latency could be predicted by the need for tocolysis, a cervical length less than 25 mm at admission and the existence of anamnios. Outpatient follow-up was not found to lead to increased maternal morbidity or neonatal mortality. CONCLUSION: Our study highlights predictive factors of short latency exceeding 48 h after PPROM. Knowledge of these factors may provide justification for outpatient monitoring of patients presenting with a long cervix, absence of need for tocolysis and persistence of amniotic fluid and, thus, no risk factors after 48 h of admission.

Induction of labour in case of premature rupture of membranes at term with an unfavourable cervix: protocol for a randomised controlled trial comparing double balloon catheter (+oxytocin) and vaginal prostaglandin (RUBAPRO) treatments.

INTRODUCTION: Premature rupture of membranes (PROM) occurs at term in 8% of pregnancies. Several studies have demonstrated that the risk of chorioamnionitis and neonatal sepsis increases with duration of PROM. Decreasing the time interval between PROM and delivery is associated with lower rates of maternal infections. In case of an unfavourable cervix, the use of prostaglandin for cervical maturation demonstrates some advantages over oxytocin. The use of double balloon catheter in reduction of PROM duration has not been evaluated in the literature. METHODS AND ANALYSIS: We are conducting a prospective, monocentric, randomised clinical trial on pregnant women with an unfavourable cervix showing PROM at term (RUBAPRO).After 12-24 hours of PROM, women are randomly assigned to one group treated with a double balloon catheter for 12 hours, with oxytocin administered after 6 hours or to the control group treated with 24 hours of vaginal prostaglandin followed by oxytocin infusion alone. Patients (n=80) are randomised at a 1:1 ratio with stratification on parity.The inclusion criteria are a Bishop score of <6, cephalic presentation at term and confirmed PROM. Women with suspected chorioamnionitis; group B streptococcus (GBS) carrier; a history of caesarean delivery or any contraindication for vaginal delivery are excluded.The time from induction to delivery is the primary outcome. Secondary outcomes were mode of delivery, maternofetal morbidity and the effect of parity on strategies for reduction of PROM duration.To sufficiently demonstrate a difference (10 hours) between groups-with a statistical power of 90% and a two-tailed α of 5%-40 patients per group will be required. ETHICS AND DISSEMINATION: Written informed consent is required from participants.National Ethics Committee approval was obtained in August 2017. The results will be published in a peer-reviewed journal and presented at relevant conferences. Access to raw data will be available only to members of the research team. TRIAL REGISTRATION NUMBER: NCT03310333.

Retinoic Acid Pathway Regulation of Vascular Endothelial Growth Factor in Ovine Amnion.

Vascular endothelial growth factor (VEGF) has been proposed as an important regulator of amniotic fluid absorption across the amnion into the fetal vasculature on the surface of the placenta. However, the activators of VEGF expression and action in the amnion have not been identified. Using the pregnant sheep model, we aimed to investigate the presence of the retinoic acid (RA) pathway in ovine amnion and to determine its effect on VEGF expression. Further, we explored relationships between RA receptors and VEGF and tested the hypothesis that RA modulates intramembranous absorption (IMA) through induction of amnion VEGF in sheep fetuses subjected to altered IMA rates. Our study showed that RA receptor isoforms were expressed in sheep amnion, and RA response elements (RAREs) were identified in ovine RARß and VEGF gene promoters. In ovine amnion cells, RA treatment upregulated RARß messenger RNA (mRNA) and increased VEGF transcript levels. In sheep fetuses, increases in IMA rate was associated with elevated VEGF mRNA levels in the amnion but not in the chorion. Further, RARß mRNA was positively correlated with VEGF mRNA levels in the amnion and not chorion. We conclude that an RA pathway is present in ovine fetal membranes and that RA is capable of inducing VEGF. The finding of a positive relationship between amnion VEGF and RARß during altered IMA rate suggests that the retinoid pathway may play a role through VEGF in regulating intramembranous transport across the amnion.

Cigarette smoke condensate affects the retinoid pathway in human amnion.

INTRODUCTION: The preterm premature rupture of membranes (PPROM) is a frequent pathology responsible of more than 30% of preterm births. Tobacco smoking is one of the most frequently described risk factors identified and contributes to the pre term weakening of fetal membranes. As previously demonstrated, all-trans retinoic acid (atRA) regulates several genes involved in the extracellular matrix dynamics, an essential actor in fetal membrane ruptures. We hypothesized that cigarette smoke may affect this pathway in human amnion. METHODS: Amnion was obtained from full-term fetal membranes collected from non-smoking women after cesarean births and used either as explants or for the isolation of derived epithelial cells. The pro-healing and transcriptomic effects of atRA were studied by a scratch assay experiment and quantitative RT-PCR, respectively, after treatment with dimethyl sulfoxyde (DMSO), atRA, DMSO + cigarette smoke condensate (CSC), or atRA + CSC. RESULTS: Our results show a strong alteration of the retinoid pathway after CSC treatment on amnion-derived epithelial cells and explants. We first demonstrated that CSC inhibits the activity of the RARE reporter gene in amnion-derived epithelial cells. Then, atRA's effects on both the transcription of its target genes and wound healing were demonstrated to be inhibited or at least decreased by the CSC in human amnion epithelial cells. DISCUSSION: Here, we demonstrated that CSC altered the retinoid signal, already known to have roles in fetal membrane physiopathology. These results highlight a potential negative action of maternal smoking on the retinoid pathway in human amnion and more generally on pregnancy.

All-trans retinoic acid promotes wound healing of primary amniocytes through the induction of LOXL4, a member of the lysyl oxidase family.

Thirty percent of preterm births directly result from preterm premature rupture of fetal membranes (PPROM). Clinical management currently proposes using a collagen plug to mechanically stop loss of amniotic fluid. Vitamin A and its active metabolite (retinoic acid) have well-known pro-healing properties and could thus make good candidates as a proposable adjuvant to this mechanical approach. Here we investigate the molecular mechanisms involved in the pro-healing properties of all-trans retinoic acid (atRA) in fetal membranes via an approach using an in vitro primary amniocyte wound model and transcriptomics. The results demonstrate that atRA promotes migration in primary amniocytes, improving wound healing in vitro by up to 90%. This effect is mediated by the induction of LOXL4, which plays a crucial role in the dynamics of the extracellular matrix by regulating collagen reticulation. This new insight into how atRA exerts its pro-healing properties prompts us to propose using atRA as a candidate strategy to help prevent future PPROM.

Lysyl oxidase-like 4 involvement in retinoic acid epithelial wound healing.

Vitamin A and its active forms (retinoic acids/RAs) are known to have pro-healing properties, but their mechanisms of action are still poorly understood. This work aimed to identify the cellular and molecular processes by which atRA (all-trans RA) improves wound healing, using an in vivo model of mouse corneal alkali burns and an in vitro cellular human corneal epithelial injury model. Regulation by atRA has been studied on most of the cellular events that occur in wound healing. We investigated the direct influence of atRA on a specific target gene known to be involved in the extracellular matrix (ECM) dynamics, one of the pathways contributing to epithelial repair. Our results demonstrate that atRA promotes corneal epithelial wound healing by acting preferentially on migration. The induction of lysyl oxidase-like 4 (LOXL4) expression by atRA in the corneal epithelium environment was established as essential in the mechanism of atRA-dependent wound healing. Our study describes for the first time a direct link between a retinoic-induced gene and protein, LOXL4, and its general clinical pro-healing properties in ECM dynamics.

Nuclear retinoid receptors and pregnancy: placental transfer, functions, and pharmacological aspects.

Animal models of vitamin A (retinol) deficiency have highlighted its crucial role in reproduction and placentation, whereas an excess of retinoids (structurally or functionally related entities) can cause toxic and teratogenic effects in the embryo and foetus, especially in the first trimester of human pregnancy. Knock-out experimental strategies-targeting retinoid nuclear receptors RARs and RXRs have confirmed that the effects of vitamin A are mediated by retinoic acid (especially all-trans retinoic acid) and that this vitamin is essential for the developmental process. All these data show that the vitamin A pathway and metabolism are as important for the well-being of the foetus, as they are for that of the adult. Accordingly, during this last decade, extensive research on retinoid metabolism has yielded detailed knowledge on all the actors in this pathway, spurring the development of antagonists and agonists for therapeutic and research applications. Natural and synthetic retinoids are currently used in clinical practice, most often on the skin for the treatment of acne, and as anti-oncogenic agents in acute promyelocytic leukaemia. However, because of the toxicity and teratogenicity of retinoids during pregnancy, their pharmacological use needs a sound knowledge of their metabolism, molecular aspects, placental transfer, and action.

Preanalytical, analytical, gestational and pediatric aspects of the S100B immuno-assays.

BACKGROUND: Traumatic brain injury management is a tricky issue in children and pregnant women (due to adverse effects of computer tomography). To facilitate management, we report the main analytical performances and reference ranges for blood tests for the well-established S100B biomarker in under-16 children on a DiaSorin® Liaison XL analyzer and in pregnant women on DiaSorin® Liaison XL and Roche Diagnostics® Cobas e411 analyzers. METHODS: Serum S100B concentrations were determined by chemiluminescent immunoassay on a DiaSorin® analyzer in a population of 409 healthy children aged 0-16 years and on DiaSorin®/Roche Diagnostics® instruments in a population of 50 pregnant women (one blood sample for each trimester). The analytical performances of both instruments and the influence of blood cells and skin pigmentation on the assay were also studied. RESULTS: For children, four age-groups emerged, i.e. 0-3 months (mean: 0.97 µg/L; standard deviation (SD): 0.36; 95th percentile: 1.55), 4-9 months (mean: 0.58 µg/L; SD: 0.30; 95th: 1.18), 10-24 months (mean: 0.31 µg/L; SD: 0.12; 95th: 0.54) and 2-16 years (mean: 0.20 µg/L; SD: 0.07; 95th: 0.32). For pregnant women, serum S100B concentrations were similar to defined ranges for adults and not significantly different between trimesters on DiaSorin® (p=0.652)/Roche Diagnostics® (p=0.877) analyzers. We also found S100B expression (protein, total mRNA) in lymphocytes, an influence of skin pigmentation, and good analytical performances for both instruments. CONCLUSIONS: Data provided here is useful for interpreting serum S100B test results, in terms of preanalytical conditions, analytical performances, pediatric and pregnancy' environment.

Aquaporins and Fetal Membranes From Diabetic Parturient Women: Expression Abnormalities and Regulation by Insulin.

CONTEXT: During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling the homeostasis of the amniotic volume, but their regulation by insulin was never explored in diabetic women. OBJECTIVE: The aim of our study was to investigate the involvement of AQPs 1, 3, 8, and 9 expressed in fetal membranes in diabetic parturient women and the control of their expression by insulin. DESIGN AND PARTICIPANTS: From 129 fetal membranes in four populations (controls, type 1, type 2 [T2D], and gestational diabetes [GD]), we established an expression AQP profile. In a second step, the amnion was used to study the control of the expression and functions of AQPs 3 and 9 by insulin. MAIN OUTCOMES AND MEASURES: The expression of transcripts and proteins of AQPs was studied by quantitative RT-PCR and ELISA. We analyzed the regulation by insulin of the expression of AQPs 3 and 9 in the amnion. A tritiated glycerol test enabled us to measure the impact of insulin on the functional characteristics. Using an inhibitor of phosphatidylinositol 3-kinase, we analyzed the insulin intracellular signaling pathway. RESULTS: The expression of AQP3 protein was significantly weaker in groups T2D and GD. In nondiabetic fetal membranes, we showed for the amnion (but not for the chorion) a significant repression by insulin of the transcriptional expression of AQPs 3 and 9, which was blocked by a phosphatidylinositol 3-kinase inhibitor. CONCLUSION: In fetal membranes, the repression of AQP3 protein expression and functions observed in vivo is allowed by the hyperinsulinism described in pregnant women with T2D or GD.