Redundant roles of AKT1 and AKT2 in fertility, estrous cyclicity and endometrial gland development.

In brief: The regulation of AKT in the endometrium during many cellular processes such as apoptosis and cell survival is crucial during the estrous cycle to ensure fertility. This research shows the specific function of AKT isoforms in the mouse endometrium for litter size, estrous cyclicity and endometrial gland development. Abstract: Apoptosis and cell survival regulation are crucial processes during the estrous cycle to prepare a receptive uterus during implantation for successful recognition of pregnancy. PI3K/AKT signaling has a crucial role during gestation, and AKT isoforms (1, 2 or 3) are regulated differently in the endometrium during the estrous cycle and embryo implantation. However, the specific roles of these isoforms are still unclear. We have previously shown that AKT isoforms expression during the rat estrous cycle and gestation is differently regulated. The present study aimed to establish the specific role of AKT isoforms in the mouse uterus. The hypothesis is that dysregulation of AKT isoforms expression could cause fertility-related issues in an isoform-specific manner. With four different mouse models and in-house crossbreeding, all isoforms KO combinations (single, double and triple) were obtained in progesterone receptor-expressing tissues. The results demonstrated that in absence of one or more AKT isoforms, female fertility was decreased. Mainly, we have observed smaller litter size, specifically in Akt1-2 KO mice. Additionally, we have found Akt1-2-3 KO mice to be fully infertile. Estrous cyclicity was also disrupted in Akt1-2 KO mice with longer diestrus stage. Moreover, the number of endometrial glands was decreased throughout the estrous cycle suggesting an important role in gland development for AKT1 and AKT2. Our results suggest not only specific roles between each isoform but also a partially redundant function of AKT1 and AKT2 in litter size, estrous cyclicity and endometrial gland development. This highlights the importance of AKT in the physiological regulation of mouse fertility.

Transactional associations between vocabulary and disruptive behaviors during the transition to formal schooling.

This study investigated the transactional relations between vocabulary and disruptive behaviors (DB; physical aggression and opposition/rule breaking/theft and vandalism), during the transition to formal schooling, using a community sample of 572 children. Cross-lagged panel model analyses were used to examine bidirectional relationships, comparing physical aggression to non-aggressive DB. Transactional associations between vocabulary and DB were observed, coinciding with school entry. Lower vocabulary in preschool (60mo.) was predictive of higher physical aggression scores in kindergarten. In turn, higher physical aggression in kindergarten was predictive of lower vocabulary in 1st grade. For non-aggressive DB, recurrent associations were found. Lower verbal skills in preschool (42mo.) and kindergarten predicted higher non-aggressive DB scores later in preschool and in 1st grade respectively. In turn, higher non-aggressive DB in kindergarten predicted lower vocabulary scores in 1st grade. In contrast to transactional paths from vocabulary to DB, transactional paths from DB to vocabulary observed after the transition to elementary school remained significant after controlling for comorbid hyperactivity, impulsivity and inattention behaviors, suggesting these links were specific to aggressive and non-aggressive DB. Practical implications for prevention are discussed.

Transactional longitudinal relations between accuracy and reaction time on a measure of cognitive flexibility at 5, 6, and 7 years of age.

Whereas accuracy is used as an indicator of cognitive flexibility in preschool-age children, reaction time (RT), or a combination of accuracy and RT, provide better indices of performance as children transition to school. Theoretical models and cross-sectional studies suggest that a speed-accuracy tradeoff may be operating across this transition, but the lack of longitudinal studies makes this transition difficult to understand. The current study explored the longitudinal and bidirectional associations between accuracy and RT on the DCCS (mixed block) at 5, 6, and 7 years of age using cross-lagged panel analyses. The study also examined the roles of working memory and language, as potential longitudinal mediators between RT at Time X and accuracy at Time X + 1, and explored the role of inhibitory control. The sample consisted of 425 children from the Quebec Longitudinal Study of Child Development. Results show lagged associations from slower RT to greater improvements in accuracy between 5 and 6 years and between 6 and 7 years. Further, higher accuracy at 6 years predicted faster RT at 7 years. Only working memory acted as a partial mediator between RT at 5 years and accuracy at 6 years. These results provide needed longitudinal evidence to support theoretical claims that slower RT precedes improved accuracy in the development of cognitive flexibility, that working memory may be involved in the early stage of this process, and that accuracy and reaction time become more efficient in later stages of this process.

The 3D-Transition Study: Objectives, Methods, and Implementation of an Innovative Planned Missing-Data Design.

The prevalence of mental health problems represents a significant burden on school and community health resources as early as preschool. Reducing this burden requires a better understanding of the developmental mechanisms linking children's early vulnerabilities with mental health after the transition to formal schooling. The 3D-Transition Study (2017-2021) follows 939 participants from a pregnancy cohort in the province of Québec, Canada, as they transition to kindergarten and first grade to examine these mechanisms. Biannual assessments include completed questionnaires from 2 parents as well as teachers, parent-child observations, anthropometric measurements, and age-sensitive cognitive assessments. Saliva is also collected on 11 days over a 16-month period in a subsample of 384 participants to examine possible changes in child salivary cortisol levels across the school transition and their role in difficulties observed during the transition. A combination of planned missing-data designs is being implemented to reduce participant burden, where incomplete data are collected without introducing bias after the use of multiple imputation. The 3D-Transition Study will contribute to an evidence-based developmental framework of child mental health from pregnancy to school age. In turn, this framework can help inform prevention programs delivered in health-care settings during pregnancy and in child-care centers, preschools, and schools.

Externalizing Risk Pathways for Adolescent Substance Use and Its Developmental Onset: A Canadian Birth Cohort Study: Trajectoires de comportements extériorisés et le risque pour l'initiation et l'usage de substances des adolescents : Une étude de cohorte de naissance canadienne.

OBJECTIVE: Only a minority of drug and alcohol users develops a substance use disorder. Previous studies suggest that this differential vulnerability commonly reflects a developmental trajectory characterized by diverse externalizing behaviors. In this study, we examined the relation between child and adolescent externalizing behaviors and adolescent substance use in a prospectively followed Canadian birth cohort, accounting for the temporal sequence of a wide variety of contributing factors. METHODS: Two hundred and forty-two adolescents followed since birth (date range: 1996 to 2012) were assessed on externalizing behavior (age 17 months to 16 years), alcohol and cannabis use at age 16, age of alcohol use onset, family history of substance use problems, family functioning (age 11 to 15), sensation seeking (age 16), prenatal substance exposure, socioeconomic status (age 1 to 9), and sex. RESULTS: Age of alcohol use onset was predicted by a family history of substance use problems, externalizing traits from ages 6 to 10 and 11 to 16, sensation seeking at age 16, prenatal alcohol and tobacco exposure and family functioning at ages 11 to 15. High frequencies of alcohol and cannabis use at age 16 were both predicted by externalizing traits from ages 11 to 16, a family history of substance use problems and sensation seeking after controlling for other individual, environmental and familial variables. The association between familial substance use problems and substance use during adolescence was partially mediated by externalizing traits from age 11 to 16. CONCLUSIONS: The present findings provide prospective evidence for a developmental risk pathway for adolescent substance use, potentially identifying those who could benefit from early interventions.

Moderation of parenting by inhibitory control in the prediction of the common and unique variance of hyperactivity-impulsivity and inattention.

This study examined whether the interaction between parenting and inhibitory control predicts hyperactivity-impulsivity and inattention in 195 children. Observation data of positive parenting were collected at 4 years, and mother reports of coercive parenting at 5 years, inhibitory control at 6 years, and hyperactivity-impulsivity/inattention at 7 years were obtained. The common and unique variance of hyperactivity-impulsivity and inattention symptoms were examined as outcomes using a bifactor model. Results indicated that positive parenting practices predicted lower levels of hyperactivity-impulsivity/inattention behaviors at age 7 only when children's inhibitory control was high. These results support the vantage sensitivity model, which posits that some individuals show an increased sensitivity to positive experiences exclusively, and support the appropriateness of a targeted prevention approach in early childhood.

The Interactive Effects of Parental Knowledge with Impulsivity and Sensation Seeking in Adolescent Substance Use.

This study examined whether interactions of parental knowledge of adolescent's whereabouts with impulsivity and sensation seeking in the prediction of adolescent substance use supported the diathesis-stress or differential susceptibility model in 230 15-year old adolescents (53% girls). Interactions between impulsivity and parental knowledge supported the diathesis-stress model with high impulsivity as a vulnerability factor: when impulsivity was higher, low levels of parental knowledge were associated with higher levels of substance use. Interactions between sensation seeking and parental knowledge supported differential susceptibility with low sensation seeking as a susceptibility factor; low parental knowledge was associated with higher substance use and high parental knowledge with lower substance use when sensation seeking was lower. Our results show that impulsivity and sensation seeking should be considered independently. Results support previous research suggesting that impulsivity in adolescence may act as a vulnerability factor and suggests that low sensation seeking may be a susceptibility factor.

Modelling vocabulary development among multilingual children prior to and following the transition to school entry.

Differences between monolingual and multilingual vocabulary development have been observed but few studies provide a longitudinal perspective on vocabulary development before and following school entry. This study compares vocabulary growth profiles of 106 multilingual children to 211 monolingual peers before and after school entry to examine whether: (1) school entry coincides with different rates of vocabulary growth compared to prior to school entry, (2) compared to monolingual peers, multilingual children show different vocabulary sizes or rates of vocabulary growth, (3) the age of onset of second-language acquisition for multilingual children is associated with vocabulary size or rate of vocabulary growth, and (4) the sociolinguistic context of the languages spoken by multilingual children is associated with vocabulary size or rate of vocabulary growth. Results showed increases in vocabulary size across time for all children, with a steeper increase prior to school entry. A significant difference between monolingual and multilingual children who speak a minority language was observed with regards to vocabulary size at school entry and vocabulary growth prior to school entry, but growth rate differences were no longer present following school entry. Taken together, results suggest that which languages children speak may matter more than being multilingual per se.

Inhibition of CRM1 activity sensitizes endometrial and ovarian cell lines to TRAIL-induced cell death.

BACKGROUND: CRM1 enrichment has been shown to be indicative of invasive as well as chemoresistant tumors. On the other hand, TRAIL, a powerful and specific anti-tumoral agent, has yet to be used effectively to treat gynecological tumors in patients. In the present study, we examined if CRM1, a nuclear exporter capable of mediating protein transport, could be a relevant target to restore chemosensitivity in chemoresistant cells. We thus explored the hypothesis that CRM1-driven nuclear exclusion of tumor suppressors could lead to chemoresistance and that CRM1 inhibitors could present a novel therapeutic approach, allowing sensitization to chemotherapeutic agents. METHODS: Ovarian cancer cell lines, as well as endometrial cancer cell lines, were treated with leptomycin B (LMB), cisplatin and TRAIL, either singly or in combination, in order to induce apoptosis. Western blot and flow cytometry analysis were used to quantify caspases activation and apoptosis induction. Immunofluorescence was used to determine nuclear localization of p53. Colony formation assays were performed to determine therapeutic effectiveness; p53 siRNA were used to establish p53 role in sensitization. Additional information from GEO database and Prognoscan allowed us to contextualise the obtained results. Finally, qRT-PCR was performed to measure apoptotic regulators expression. RESULTS: TRAIL and LMB combination therapy lead to cleavage of caspase-3 as well as the appearance of cleaved-PARP, and thus, apoptosis. Further experiments suggested that sensitization was achieved through the synergistic downregulation of multiple inhibitor of apoptosis, as well as the activation of apoptotic pathways. p53 was enriched in the nucleus following LMB treatments, but did not seem to be required for sensitization; additional experiments suggested that p53 opposed the apoptotic effects of LMB and TRAIL. Results obtained from public data repositories suggested that CRM1 was a driver of chemoresistance and poor prognostic; DR5, on the other hand, acted as as a marker of positive prognostic. CONCLUSIONS: Taken together, our results suggest that the use of CRM1 inhibitors, in combination to chemotherapeutic compounds, could be highly effective in the treatment of gynecological malignancies.

Age of Cannabis Use Onset and Adult Drug Abuse Symptoms: A Prospective Study of Common Risk Factors and Indirect Effects.

The present study examined 1) whether the associations between cannabis use (CU) age of onset and drug abuse by 28 y remain when controlling for risk factors in childhood, adolescence and early adulthood; and 2) the developmental pathways from early risk factors to drug abuse problems. Participants from a longitudinal sample of boys of low socioeconomic status ( N = 1,030) were followed from 6 to 28 y. We examined the self-reported CU onset between the ages of 13 and 17 y and drug abuse symptoms by 28 y. The odds of developing any drug abuse symptoms by 28 y were reduced by 31% for each year of delayed CU onset (OR = 0.69). Cannabis, alcohol and other drug frequency at 17 y mediated this association. Still, even when taking that frequency of use into account, adolescents who started using cannabis before 15 y were at a higher risk of developing drug abuse symptoms by age 28 y. Significant indirect effects were found from early adolescent delinquency and affiliation with deviant friends to drug abuse symptoms at 28 y through CU age of onset and substance use frequency at 17 y. The results suggest more clearly than before that prevention programs should aim at delaying CU onset to prevent or reduce drug abuse in adulthood. Furthermore, prevention programs targeting delinquency and/or affiliation with deviant friends in childhood or early adolescence could indirectly reduce substance abuse in adulthood without addressing substance use specifically.

Commentary: On the importance of looking at nonlinearity and developmental effects - a reflection on Flom et al. (2017).

By examining both linear and curvilinear associations between mental development and activity level, the study by Flom et al. (Journal of Child Psychology and Psychiatry, 2017) highlights the importance of going beyond linear associations in psychological fields of research. Results from Flom et al. (Journal of Child Psychology and Psychiatry, 2017) also raise interesting questions for future research. First, studies should look at variables that may explain the associations between activity level and mental development, such as self-regulation and attention. Second, longitudinal changes in the strength of the association between activity level and mental development should be examined to determine when this association is at its strongest. Finally, longitudinal research looking at bidirectional effects is needed to confirm the direction of the associations between activity level and mental development. Answers to these questions will allow the identification of the best targets and developmental periods for interventions to take place.

Adolescent cannabis use, change in neurocognitive function, and high-school graduation: A longitudinal study from early adolescence to young adulthood.

The main objective of this prospective longitudinal study was to investigate bidirectional associations between adolescent cannabis use (CU) and neurocognitive performance in a community sample of 294 young men from ages 13 to 20 years. The results showed that in early adolescence, and prior to initiation to CU, poor short-term and working memory, but high verbal IQ, were associated with earlier age of onset of CU. In turn, age of CU onset and CU frequency across adolescence were associated with (a) specific neurocognitive decline in verbal IQ and executive function tasks tapping trial and error learning and reward processing by early adulthood and (b) lower rates of high-school graduation. The association between CU onset and change in neurocognitive function, however, was found to be accounted for by CU frequency. Whereas the link between CU frequency across adolescence and change in verbal IQ was explained (mediated) by high school graduation, the link between CU frequency and tasks tapping trial and error learning were independent from high school graduation, concurrent cannabis and other substance use, adolescent alcohol use, and externalizing behaviors. Findings support prevention efforts aimed at delaying onset and reducing frequency of CU.

Adaptation and Validation of the Life Events and Difficulties Schedule for Use With High School Dropouts.

The Life Events and Difficulties Schedule (LEDS) is considered the standard for measuring psychosocial stressor exposure, but it has not been used with academically at-risk adolescents, including high school dropouts. The goal of this study was to (1) adapt the LEDS for use with this population, and (2) examine the reliability (interrater) and validity (concurrent and predictive) of this adaptation among a sample of vulnerable adolescents (N = 545). Good reliability coefficients (.79-.90) were obtained, and stressor exposure was associated with concurrent criteria indexing mental health outcomes (depression) and major risk factors for dropout (administratively recorded and self-reported). Also, LEDS scores predicted dropout beyond these risk factors. The adapted LEDS appears useful for describing academically struggling adolescents' stressor exposure.

Differential susceptibility to environmental influences: Interactions between child temperament and parenting in adolescent alcohol use.

Temperament and parental practices (PP) are important predictors of adolescent alcohol use (AU); however, less is known about how they combine to increase or decrease risk of AU. This study examined whether age 6 temperament (i.e., impulsivity and inhibitory control) interacted with age 6 coercive PP and/or age 14 parental monitoring to predict AU at 15 years among 209 adolescents. Results showed that low parental monitoring was associated with more frequent AU and that coercive PP interacted with impulsivity to predict AU. This interaction was examined as a function of two models that were not studied before in the prediction of AU: the diathesis-stress model (i.e., impulsive children are more "vulnerable" to adverse PP than those with an easy temperament); and the differential susceptibility model (i.e., impulsive children are also more likely to benefit from good PP). Results supported the differential susceptibility model by showing that impulsive children were not only at higher risk for AU when combined with high coercive PP but also benefit from the absence of coercive PP. This supports the suggestion that the conception of certain temperament characteristics, or in this case impulsivity, as a "vulnerability" for adolescent AU, may need revision because it misrepresents the malleability it may imply.

Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer.

Three-dimensional (3D) in vitro models have an invaluable role in understanding the behaviour of tumour cells in a well defined microenvironment. This is because some aspects of tumour characteristics cannot be fully recapitulated in a cell monolayer (2D). In the present study, we compared growth patterns, expression of signalling molecules, and metabolism-associated proteins of endometrial cancer cell lines in 3D and 2D cell cultures. Cancer cells formed spherical structures in 3D reconstituted basement membrane (3D rBM), and the morphological appearance was cell line dependent. Cell differentiation was observed after 8 days in the 3D rBM. There was reduced proliferation, detected by less expression of PCNA in 3D rBM than in 2D cell monolayers. The addition of exogenous epidermal growth factor (EGF) to cancer cells induced phosphorylation of EGFR and Akt in both cell culture conditions. The uptake of glucose was selectively altered in the 3D rBM, but there was a lack of association with Glut-1 expression. The secretion of vascular endothelial growth factor (VEGF) and prostaglandin E(2) (PGE(2)) was selectively altered in 3D rBM, and it was cell line dependent. Our data demonstrated that 3D rBM as an in vitro model can influence proliferation and metabolism of endometrial cancer cell behaviour compared to 2D cell monolayer. Changes are specific to individual cell types. The use of 3D rBM is, therefore, important in the in vitro study of targeted anticancer therapies.

Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth.

Maternal separation and poor maternal care in animals have been shown to have important effects on the developing hippocampus and amygdala. In humans, children exposed to abuse/maltreatment or orphanage rearing do not present changes in hippocampal volumes. However, children reared in orphanages present enlarged amygdala volumes, suggesting that the amygdala may be particularly sensitive to severely disturbed (i.e., discontinous, neglectful) care in infancy. Maternal depressive symptomatology has been associated with reductions in overall sensitivity to the infant, and with an increased rate of withdrawn, disengaged behaviors. To determine if poor maternal care associated with maternal depressive symptomatology has a similar pattern of association to the volumes of the hippocampus and amygdala in children, as is the case for severely disturbed infant care (orphanage rearing), we measured hippocampal and amygdala volumes as well as stress hormone (glucocorticoid) levels in children exposed (n = 17) or not (n = 21) to maternal depressive symptomatology since birth. Results revealed no group difference in hippocampal volumes, but larger left and right amygdala volumes and increased levels of glucocorticoids in the children of mothers presenting depressive symptomatology since birth. Moreover, a significant positive correlation was observed between mothers' mean depressive scores and amygdala volumes in their children. The results of this study suggest that amygdala volume in human children may represent an early marker of biological sensitivity to quality of maternal care.

Longitudinal Study of Early Adversity and Disturbing Dream Frequency: Moderating Role of Early Negative Emotionality.

Although disturbing dreams are prevalent in youth and are associated with psychopathology, little is known about their developmental course and risk factors. We aimed to examine the association between early social environment and subsequent disturbing dream frequency across adolescence as moderated by early negative emotionality. Measures of children's early social environment and negative emotionality were collected from the mothers of 410 children (5-42 months old) and measures of disturbing dream frequency directly from the children (13-18 years old). Preliminary steps identified subgroups of families with distinct profiles of social environment using latent variable mixture modeling, and captured changes in disturbing dream frequency using latent growth modeling. Regression and moderation analyses were conducted to test the study objectives. Results showed that the diverse family patterns were best captured by two profiles reflecting adverse and positive social environments and that overall disturbing dream frequency decreased during adolescence. Moderation analyses showed that when early negative emotionality was higher, DD frequency was not only more elevated in an adverse environment, but lower in a positive environment. These results indicate that the development of disturbing dreams is most strongly associated with a combination of individual and environment factors. Our study adds to the literature by refining our conception of individual traits and disturbing dream development and has implications for the prevention of bad dreams, nightmares, and associated psychopathologies.

The Role of Executive Function at 6 Years in the Association between Behavioral Inhibition at 5 Years and Anxiety at 7 Years.

EF skills play a central role in the etiology and maintenance of anxiety, but it is unclear whether they act as moderators or mediators in the relation between early behavioral inhibition (BI) and later anxiety. The current study tested two models by examining whether two executive functions (EF) skills (cognitive flexibility and working memory) assessed at age 6 acted as moderators or mediators in the relation between BI at 5 years and anxiety symptoms at 7 years. The sample consisted of 422 children from the Quebec Longitudinal Study of Child Development. We tested the moderation model, main and interaction effects using hierarchical multiple regression analyses and the mediation model with the product of coefficients test. Results showed that higher BI at 5 years predicted high anxiety at 7 years only at low levels of cognitive flexibility or working memory at 6 years. This suggests that high levels of cognitive flexibility or working memory at 6 years may act as protective factors. In contrast, neither cognitive flexibility nor working memory at age 6 acted as mediators in the association between BI at 5 years and anxiety at 7 years. Results support the hypothesis that goal-driven cognitive control processes act as moderators and promote adaptive functioning by dampening the effect of early BI on later anxiety.

Emotion Dysregulation Is Associated With Increased Problem Cannabis Use Among Emerging Adults During COVID-19.

OBJECTIVE: Emerging adulthood (18-25 years) is associated with peak prevalence of cannabis use. Although population-based longitudinal studies have found little change in cannabis use among emerging adults during COVID-19, research examining changes among vulnerable subgroups is lacking. The present study examined the association between emotion dysregulation at 23 years and change in cannabis use frequency and problem cannabis use among a large sample of emerging adults, from before to during the COVID-19 pandemic. METHOD: Longitudinal data were analyzed from 1,226 emerging adults (59% female; n = 738 reported cannabis use) who completed online surveys before the pandemic (2019; age 21) and 1 year into COVID-19 (2021; age 23) as part of the Québec Longitudinal Study of Child Development. RESULTS: There was no significant overall within-person change in cannabis use outcomes during COVID-19 among the emerging adult sample. However, emotional clarity (a dimension of emotion dysregulation) at 23 years significantly moderated change in problem cannabis use during COVID-19. Namely, low emotional clarity at 23 years was associated with increased problem cannabis use (B = 0.79, 95% CI [0.23, 1.34]), whereas high emotional clarity at 23 years was associated with decreased problem cannabis use (B = -0.68, 95% CI [-1.27, -0.09]) during COVID-19, among men only. CONCLUSIONS: Findings highlight the need to consider changes in cannabis use during COVID-19 among emerging adults with elevated emotion dysregulation (and particularly, low emotional clarity among men) and reiterate the need for supports and targeted interventions to reduce cannabis use and decrease associated harms as society emerges from COVID-19.

Regulation of the PI3-K/Akt survival pathway in the rat endometrium.

The occurrence of apoptosis and cell survival in the receptive uterus is intimately involved in the embryo implantation process in order to facilitate embryo attachment to the maternal endometrium. The initial stimulus leading to successful implantation might be triggered by the conceptus itself. By the end of rat embryo implantation, decidualization begins, followed by the regression of the decidua basalis on Day 14. The phosphatidylinositol 3-kinase (PI3-K) survival pathway and TGF-beta have been thought to play a role in this process. The objective of the present study was to investigate the regulation of the PI3-K/PTEN/Akt pathway in rat endometrium during pregnancy. Rats were killed on different days of pregnancy (Day 1-22 and postpartum) or pseudopregnancy (Day 1-9), and uteri were removed to collect endometrial tissues. The active form of Akt (pAkt) was increased at Day 5 of pregnancy and at Day 3 of pseudopregnancy as well as at Day 12 of pregnancy and at Day 1 postpartum. Of the three Akt isoforms (Akt1, Akt2, and Akt3), Akt3 was the only isoform phosphorylated at Day 5 during the implantation process and at postpartum as demonstrated by immunoprecipitation studies. PI3-K inhibition in vivo blocked Akt phosphorylation, reduced Smad2 phosphorylation, and reduced both TGF-beta2 and XIAP expression. PI3-K inhibition in cultured decidual cells led to inhibition of pAkt and decrease XIAP expression. These results suggest that Akt and XIAP may be important surviving signaling molecules by which apoptosis is regulated in the rat endometrium during pregnancy and that TGF-beta could be linked to this process.