Search

Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P) + metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD + metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials. Importantly, treatment of a triple-negative breast cancer mouse model with the NAD + precursor nicotinamide mononucleotide (NMN) reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Overall, these findings raise the possibility that NAD + precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy., (© 2024. The Author(s).)

Purpose: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM)., Methods: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24-28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls., Results: OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM., Conclusion: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells., (© 2024. The Author(s).)

Objective: To evaluate oocyte retrieval experiences and side effects under minimally controlled ovarian stimulation (COS) treatment for in vitro maturation (IVM) of oocytes compared with conventional COS treatment., Design: A retrospective survey study., Setting: Clinical in vitro fertilization treatment center., Patient(s): Data were collected from subjects undergoing minimal COS treatment (n = 110; 600-800 IU follicle-stimulating hormone) for IVM of oocytes and conventional COS treatment for egg donation (n = 48; 1,800-2,600 IU follicle-stimulating hormone) from April 2022 to November 2023., Intervention(s): Minimal and conventional COS treatments., Main Outcome Measure(s): The most common side effects experienced during ovarian stimulation and after oocyte pick-up, satisfaction level, and the likelihood of recommending or repeating minimal or conventional COS. Statistical analysis included Mann-Whitney U test and χ 2 tests, with a significance level., Result(s): During minimal COS treatment, most subjects did not experience breast swelling (86%), pelvic or abdominal pain (76%), nausea or vomiting (96%), and bleeding (96%). After oocyte pick-up, the majority (75%) reported no pelvic or abdominal pain. The most common side effect was abdominal swelling (52%). Compared with conventional COS cycles, minimal COS subjects reported significantly less postretrieval pain, with 33% experiencing no pain (vs. 6%) and with a reduced severe level of pain (5% vs. 19%), leading to fewer subjects requiring pain medication (25% vs. 54%). Additionally, 85% of women were very satisfied with minimal stimulation treatment and would recommend or repeat the treatment., Conclusion(s): Reducing the hormonal dose for ovarian stimulation has a beneficial effect on subjects, suggesting the combination of minimal COS treatment with IVM techniques is a well-tolerated alternative for women who cannot or do not wish to undergo conventionally controlled ovarian hyperstimulation treatment., Competing Interests: Declaration of interests M.M. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. M.M. is listed on a patent covering the use of ovarian support cells (OSCs) for in vitro maturation (IVM): US Provisional Patent Application No. 63/492,210. F.B. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. S.P. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. S.P. is listed on a patent covering the use of OSCs for IVM: US Provisional Patent Application No. 63/492,210. M.F.G. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. A.G. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. A.G. is listed on a patent covering the use of OSCs for IVM: US Provisional Patent Application No. 63/492,210. T.S. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. S.K. has nothing to disclose. B.P. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. B.P. is listed on a patent covering the use of OSCs for IVM: US Provisional Patent Application No. 63/492,210. E.G. has nothing to disclose. V.C. has nothing to disclose. A.S. has nothing to disclose. B.A. has nothing to disclose. J.K. has nothing to disclose. P.K. has nothing to disclose. D.O. has nothing to disclose. C.C.K. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. C.C.K. is listed on a patent covering the use of OSCs for IVM: US Provisional Patent Application No. 63/492,210. C.C.K. is listed on three patents covering the use of OSCs for IVM: US Patent Application No. 17/846,725, US Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K. is additionally listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, US Provisional Application No. 63/326,640, and US. Provisional Application No. 63/444,108., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Further research is needed to clarify the association of the different forms of bullying with social anxiety and social withdrawal over time in adolescents. This two-wave panel study with a 1-year time lag (October 2021-October 2022) examined the cross-lagged relationships between bullying victimization and bullying perpetration, social anxiety (i.e., fear or distress in social situations), and social withdrawal (i.e., consistent, and deliberate social solitude). Participants were 485 middle school students (234 girls) attending the seventh or eighth grade at Time 1 (T1) (M age  = 12.67 years, SD = 1.14 years). Social anxiety and social withdrawal were assessed using subscales of the Social and Emotional Competencies Evaluation Questionnaire. Bullying perpetration and bullying victimization were assessed using the Bullying and Cyberbullying Behavior Questionnaire-Short Form. The within-wave associations between the study variables were similar at T1 and Time 2 (T2), with the exception that the association between bullying perpetration and social anxiety was much weaker at T1 than at T2. The results of the path analysis showed that T1 bullying perpetration predicted T2 social anxiety, and that T1 bullying victimization predicted T2 social withdrawal. We also found a reciprocal relationship between social anxiety and social withdrawal. These findings highlight the importance of preventive and remediation interventions to reduce social anxiety in adolescents who engage in and experience bullying behavior., (© 2024 Wiley Periodicals LLC.)

Study Question: Can in vitro maturation (IVM) and developmental competence of human oocytes be improved by co-culture with ovarian support cells (OSCs) derived from human-induced pluripotent stem cells (hiPSCs)?, Summary Answer: OSC-IVM significantly improves the rates of metaphase II (MII) formation and euploid Day 5 or 6 blastocyst formation, when compared to a commercially available IVM system., What Is Known Already: IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity, while limited studies have shown a positive benefit of primary granulosa cell co-culture for IVM. We recently reported the development of OSCs generated from hiPSCs that recapitulate dynamic ovarian function in vitro., Study Design, Size, Duration: The study was designed as a basic science study, using randomized sibling oocyte specimen allocation. Using pilot study data, a prospective sample size of 20 donors or at least 65 oocytes per condition were used for subsequent experiments. A total of 67 oocyte donors were recruited to undergo abbreviated gonadotropin stimulation with or without hCG triggers and retrieved cumulus-oocyte complexes (COCs) were allocated between the OSC-IVM or control conditions (fetal-like OSC (FOSC)-IVM or media-only IVM) in three independent experimental design formats. The total study duration was 1 April 2022 to 1 July 2023., Participants/materials, Setting, Methods: Oocyte donors between the ages of 19 and 37 years were recruited for retrieval after informed consent, with assessment of anti-Mullerian hormone, antral follicle count, age, BMI and ovarian pathology used for inclusion and exclusion criteria. In experiment 1, 27 oocyte donors were recruited, in experiment 2, 23 oocyte donors were recruited, and in experiment 3, 17 oocyte donors and 3 sperm donors were recruited. The OSC-IVM culture condition was composed of 100 000 OSCs in suspension culture with hCG, recombinant FSH, androstenedione, and doxycycline supplementation. IVM controls lacked OSCs and contained either the same supplementation, FSH and hCG only (a commercial IVM control), or FOSCs with the same supplementation (Media control). Experiment 1 compared OSC-IVM, FOSC-IVM, and a Media control, while experiments 2 and 3 compared OSC-IVM and a commercial IVM control. Primary endpoints in the first two experiments were the MII formation (i.e. maturation) rate and morphological quality assessment. In the third experiment, the fertilization and embryo formation rates were assessed with genetic testing for aneuploidy and epigenetic quality in blastocysts., Main Results and the Role of Chance: We observed a statistically significant improvement (∼1.5×) in maturation outcomes for oocytes that underwent IVM with OSCs compared to control Media-IVM and FOSC-IVM in experiment 1. More specifically, the OSC-IVM group yielded a MII formation rate of 68% ± 6.83% SEM versus 46% ± 8.51% SEM in the Media control (P = 0.02592, unpaired t-test). FOSC-IVM yielded a 51% ± 9.23% SEM MII formation rate which did not significantly differ from the media control (P = 0.77 unpaired t-test). Additionally, OSC-IVM yielded a statistically significant ∼1.6× higher average MII formation rate at 68% ± 6.74% when compared to 43% ± 7.90% in the commercially available IVM control condition (P = 0.0349, paired t-test) in experiment 2. Oocyte morphological quality between OSC-IVM and the controls did not significantly differ. In experiment 3, OSC-IVM oocytes demonstrated a statistically significant improvement in Day 5 or 6 euploid blastocyst formation per COC compared to the commercial IVM control (25% ± 7.47% vs 11% ± 3.82%, P = 0.0349 logistic regression). Also in experiment 3, the OSC-treated oocytes generated blastocysts with similar global and germline differentially methylated region epigenetic profiles compared commercial IVM controls or blastocysts after either conventional ovarian stimulation., Large Scale Data: N/A., Limitations, Reasons for Caution: While the findings of this study are compelling, the cohort size remains limited and was powered on preliminary pilot studies, and the basic research nature of the study limits generalizability compared to randomized control trials. Additionally, use of hCG-triggered cycles results in a heterogenous oocyte cohort, and potential differences in the underlying maturation state of oocytes pre-IVM may limit or bias findings. Further research is needed to clarify and characterize the precise mechanism of action of the OSC-IVM system. Further research is also needed to establish whether these embryos are capable of implantation and further development, a key indication of their clinical utility., Wider Implications of the Findings: Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice. The controls used in this study are in line with and have produced similar to findings to those in the literature, and the outcome of this study supports findings from previous co-culture studies that found benefits of primary granulosa cells on IVM outcomes. The OSC-IVM system shows promise as a highly flexible IVM approach that can complement a broad range of stimulation styles and patient populations. Particularly for patients who cannot or prefer not to undergo conventional gonadotropin stimulation, OSC-IVM may present a viable path for obtaining developmentally competent, mature oocytes., Study Funding/competing Interest(s): A.D.N., A.B.F., A.G., B.P., C.A., C.C.K., F.B., G.R., K.S.P., K.W., M.M., P.C., S.P., and M.-J.F.-G. are shareholders in the for-profit biotechnology company Gameto Inc. P.R.J.F. declares paid consultancy for Gameto Inc. P.C. also declares paid consultancy for the Scientific Advisory Board for Gameto Inc. D.H.M. has received consulting services from Granata Bio, Sanford Fertility and Reproductive Medicine, Gameto, and Buffalo IVF, and travel support from the Upper Egypt Assisted Reproduction Society. C.C.K., S.P., M.M., A.G., B.P., K.S.P., G.R., and A.D.N. are listed on a patent covering the use of OSCs for IVM: U.S. Provisional Patent Application No. 63/492,210. Additionally, C.C.K. and K.W. are listed on three patents covering the use of OSCs for IVM: U.S. Patent Application No. 17/846,725, U.S Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K., M.P.S., and P.C. additionally are listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, U.S. Provisional Application No. 63/326,640, and U.S. Provisional Application No. 63/444,108. The remaining authors have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Female fertility is negatively correlated with age, with noticeable declines in oocyte quantity and quality until menopause. To understand this physiological process and evaluate human approaches for treating age-related infertility, preclinical studies in appropriate animal models are needed. Thus, we aimed to characterize an immunodeficient physiological aging mouse model displaying ovarian characteristics of different stages during women's reproductive life. NOD/SCID mice of different ages (8-, 28-, and 36-40-week-old) were employed to mimic ovarian phenotypes of young, Advanced Maternal Age (AMA), and old women (~18-20-, ~36-38-, and >45-years-old, respectively). Mice were stimulated, mated, and sacrificed to recover oocytes and embryos. Then, ovarian reserve, follicular growth, ovarian stroma, mitochondrial dysfunction, and proteomic profiles were assessed. Age-matched C57BL/6 mice were employed to cross-validate the reproductive outcomes. The quantity and quality of oocytes were decreased in AMA and Old mice. These age-related effects associated spindle and chromosome abnormalities, along with decreased developmental competence to blastocyst stage. Old mice had less follicles, impaired follicle activation and growth, an ovarian stroma inconducive to growth, and increased mitochondrial dysfunctions. Proteomic analysis corroborated these histological findings. Based on that, NOD/SCID mice can be used to model different ovarian aging phenotypes and potentially test human anti-aging treatments.

The closure of schools during the COVID-19 pandemic affected adolescents' social withdrawal and social anxiety. Yet, self-esteem may have acted as a protective factor during this period. This study aimed to compare the trajectories of social withdrawal and social anxiety before (Year 1), during (Year 2 and 3), and after (Year 4) the closure of schools imposed by the COVID-19-related lockdowns, and to investigate the association of self-esteem with these trajectories. Participants were 844 (50.6% boys) Portuguese adolescents (mean age 12.70 years, SD = 1.14). The Social and Emotional Competencies Evaluation Questionnaire (QACSE) was used to assess social withdrawal and social anxiety, while The Global Self-Esteem scale of the Self-Description Questionnaire II was used to measure self-esteem. Growth curve analysis showed that social withdrawal and social anxiety had more negative trajectories during the year in which the school closures occurred. In addition, adolescents reported higher social withdrawal after the lockdowns than before the pandemic. Higher self-esteem was associated with a more positive trajectory in social withdrawal. Therefore, the results showed the negative of impact of the closure of schools on adolescents' social anxiety and social withdrawal, and that self-esteem was a protective factor during these challenging and adverse events., (© 2023. Springer Nature Limited.)

Introduction: There is an increased call for studies analyzing how implementation quality influences Social and Emotional Learning (SEL) program effectiveness., Methods: The current dissemination study analyzed the effectiveness of the Positive Attitude Upper Middle School SEL program on a Portuguese nationwide sample composed of 813 middle school students (7th and 8th grade; 51.7% boys; M age  = 12.41, S.D.  = 1.06), from 36 classrooms ( M classroom  = 22.58; S.D.  = 2.86), distributed between the control group (179 students), and three intervention groups (643 students) that reflected low, middle, and high implementer experience (respectively, Gulbenkian Academies of Knowledge, Positive Attitude Cadaval and Positive Attitude Torres Vedras). Dosage and fidelity (as implementation quality dimensions), gender, and classroom size (as individual and classroom-level variables) were also analyzed. Self-report questionnaires were administered pre- and post-intervention and at a 6-month follow-up., Results: Multilevel models were employed, and results showed that participating in the PAUMS SEL program led to more positive trajectories in self-control, social awareness, relationship skills, and responsible decision-making when compared with control groups. Regarding implementation quality, only the implementer's experience impacted the effectiveness of the PAUMS SEL program; students in the Gulbenkian Academies of Knowledge intervention group displayed a less positive trajectory in self-control than students in the Positive Attitude Torres Vedras intervention group., Discussion: Altogether, results showed that the PAUMS SEL program is ready for dissemination in Portugal, although a higher level of implementer experience is needed to achieve the best effectiveness, and they support the importance of analyzing implementer experience in SEL programs' effectiveness studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Coelho, Marchante and Brás.)

Background: Systemic administration of soluble factors from bone marrow-derived stem cells combined with activated platelet-rich plasma (SC-PRP) restored ovarian function, mediated through paracrine signaling, in murine models of chemotherapy-induced ovarian damage and human tissue from poor responder patients. However, the effects against age-related infertility and the efficacy of local administration have not been evaluated yet., Objective: This study aimed to assess whether a single intraovarian dose of stem cells combined with activated platelet-rich plasma can recover ovarian function, oocyte quality, and developmental competence in older mice., Study Design: The effects of stem cells combined with activated platelet-rich plasma against age-related infertility were assessed following controlled ovarian stimulation in an aging murine model reproducing 3 physiological stages of women's reproductive life, namely young, advanced maternal age, and menopausal (n=12 animals per group). Female mice were randomized to receive a single intraovarian injection (10 μL/ovary) of either saline, activated platelet-rich plasma, or stem cells combined with activated platelet-rich plasma. Seven days later, the mice were stimulated, naturally mated, and sacrificed to harvest their ovaries for histologic assessment and molecular analysis and their oviducts to evaluate oocyte maturation and to assess early embryo development., Results: A single intraovarian injection of stem cells combined with activated platelet-rich plasma promoted follicle activation and development in young, advanced maternal age, and old mice. Furthermore, stem cells combined with activated platelet-rich plasma rescued fertility in older mice by enhancing the quantity and quality of ovulated mature oocytes and supporting early embryo development to the blastocyst stage in all the evaluated ages. These fertility outcomes were positively associated with mitochondrial quality, treatment-increased mitochondrial DNA copy numbers, and reduced oxidative damage and apoptosis. Finally, the effects observed by histologic analysis were supported at the proteomic level. Functional proteomic analyses revealed molecular mechanisms involved in oocyte maturation and quality, mitochondrial function, and recovery of the ovarian stroma., Conclusion: Bone marrow-derived stem cells combined with activated platelet-rich plasma is a promising treatment with the potential to improve the reproductive outcomes of women with age-related infertility, exceeding the restorative effects of platelet-rich plasma alone. Although further research in human ovarian samples is still required, the autologous nature of stem cell factors collected by noninvasive mobilization, their combination with platelet-rich plasma, and the local administration route suggest that stem cells combined with activated platelet-rich plasma treatment could be a potentially effective and safe application for future clinical practice., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Ovarian senescence is a normal age-associated phenomenon, but increasingly younger women are affected by diminished ovarian reserves or premature ovarian insufficiency. There is an urgent need for developing therapies to improve ovarian function in these patients. In this context, previous studies suggest that stem cell-secreted factors could have regenerative properties in the ovaries., Objective: This study aimed to test the ability of various human plasma sources, enriched in stem cell-secreted factors, and the mechanisms behind their regenerative properties, to repair ovarian damage and to promote follicular development., Study Design: In the first phase, the effects of human plasma enriched in bone marrow stem cell soluble factors by granulocyte colony-stimulating factor mobilization, umbilical cord blood plasma, and their activated forms on ovarian niche, follicle development, and breeding performance were assessed in mouse models of chemotherapy-induced ovarian damage (n=7 per group). In addition, the proteomic profile of each plasma was analyzed to find putative proteins and mechanism involved in their regenerative properties in ovarian tissue. In the second phase, the most effective plasma treatment was validated in human ovarian cortex xenografted in immunodeficient mice (n=4 per group)., Results: Infusion of human plasma enriched bone marrow stem cell soluble factors by granulocyte colony-stimulating factor mobilization or of umbilical cord blood plasma-induced varying degrees of microvessel formation and cell proliferation and reduced apoptosis in ovarian tissue to rescue follicular development and fertility in mouse models of ovarian damage. Plasma activation enhanced these effects. Activated granulocyte colony-stimulating factor plasma was the most potent inducing ovarian rescue in both mice and human ovaries, and proteomic analysis indicated that its effects may be mediated by soluble factors related to cell cycle and apoptosis, gene expression, signal transduction, cell communication, response to stress, and DNA repair of double-strand breaks, the most common form of age-induced damage in oocytes., Conclusion: Our findings suggested that stem cell-secreted factors present in both granulocyte colony-stimulating factor-mobilized and umbilical cord blood plasma could be an effective treatment for increasing the reproductive outcomes in women with impaired ovarian function owing to several causes. The activated granulocyte colony-stimulating factor plasma, which is already enriched in both stem cell-secreted factors and platelet-enclosed growth factors, seems to be the most promising treatment because of its most potent restorative effects on the ovary together with the autologous source., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are primary factors leading to infertility. However, there is a lack of appropriate animal models of DOR usable for assessing new therapeutic strategies. In this study, we aimed to evaluate whether chemotherapy treatment in mice could reproduce features similar of that observed in women with DOR. Twenty-one Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) female mice were allocated to 3 groups (n = 7/group): control, single dose of vehicle (Dimethyl Sulfoxide [DMSO]); DOR, single reduced chemotherapy dose; and POI, single standard chemotherapy dose. After 21 days, mice underwent ovarian hyperstimulation and mating. Part of the animals were harvested to analyze ovarian reserve, ovulation and fertilization rates, and morphology, apoptosis, and vascularization of the ovarian stroma. The remaining mice underwent multiple matings to assess pregnancy rates and litter sizes. The DOR and POI mice showed an impaired estrous cyclicity and a decrease in ovarian mass, number of follicles, Metaphase II (MII) oocytes, and embryos as well as in ovarian stroma vascularization. Mice in both models showed also an increase in the percentage of morphologically abnormal follicles, stromal degeneration, and apoptosis. Similar to that observed in DOR and POI patients, these impairments were less severe in DOR than in POI mice. None of the POI females were able to achieve a pregnancy. Meanwhile, DOR females achieved several consecutive pregnancies, although litter size was decreased when compared to controls. In conclusion, a mouse model which displayed most of the ovarian characteristics and fertility outcomes of women with DOR has been established using a single dose of chemotherapy.

Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are primary factors leading to infertility. However, there is a lack of appropriate animal models of DOR usable for assessing new therapeutic strategies. In this study, we aimed to evaluate whether chemotherapy treatment in mice could reproduce features similar of that observed in women with DOR. Twenty-one Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) female mice were allocated to 3 groups (n = 7/group): control, single dose of vehicle (Dimethyl Sulfoxide [DMSO]); DOR, single reduced chemotherapy dose; and POI, single standard chemotherapy dose. After 21 days, mice underwent ovarian hyperstimulation and mating. Part of the animals were harvested to analyze ovarian reserve, ovulation and fertilization rates, and morphology, apoptosis, and vascularization of the ovarian stroma. The remaining mice underwent multiple matings to assess pregnancy rates and litter sizes. The DOR and POI mice showed an impaired estrous cyclicity and a decrease in ovarian mass, number of follicles, Metaphase II (MII) oocytes, and embryos as well as in ovarian stroma vascularization. Mice in both models showed also an increase in the percentage of morphologically abnormal follicles, stromal degeneration, and apoptosis. Similar to that observed in DOR and POI patients, these impairments were less severe in DOR than in POI mice. None of the POI females were able to achieve a pregnancy. Meanwhile, DOR females achieved several consecutive pregnancies, although litter size was decreased when compared to controls. In conclusion, a mouse model which displayed most of the ovarian characteristics and fertility outcomes of women with DOR has been established using a single dose of chemotherapy.

Current cyberbullying literature lacks longitudinal studies clarifying its predictors and consequences. This 1-year longitudinal study investigated how social and emotional competencies develop according to Portuguese middle school students' involvement in cyberbullying, and whether class size influences this relationship. There were 455 participants (M age  = 12.58; SD = 0.94; 46% girls), and data collection through self-reports took place in three different moments during 12 months. The results showed that students involved in cyberbullying in any role displayed negative trajectories during 1 year in self-control and social awareness, while victims and bully-victims displayed a more pronounced decrease in self-esteem and relationship skills during the same period. Additionally, girls displayed higher initial social awareness levels, while larger classes were associated with higher levels of self-control and responsible decision making. These results supported the importance of conducting longitudinal research and using a multilevel approach to address this topic.

The middle school transition is a salient developmental experience impacting adolescents around the world. This study employed a randomized-controlled treatment design, with randomization at the school level, to investigate the impact of a school adjustment program for middle school transition and potential gender differences. Participants included 1147 students (M age  = 9.62; SD = 0.30, 45.7 % girls), who were assessed at four time points during the transition, regarding five dimensions of self-concept (academic, social, emotional, physical and family) and self-esteem. Parallel growth curves were employed to analyze the evolution of self-concept. Following the transition to middle school, students reported lower levels of self-concept (academic, emotional and physical) and self-esteem, while participation in the intervention led to increases in self-esteem and gains in social self-concept. No gender differences were found. These results provide preliminary evidence supporting such interventions in early middle school transitions.

The Social and Emotional Competencies Evaluation Questionnaire-Teacher's version, Short Form (QACSE-P-SF) allows teachers to assess their students' social and emotional competencies, having been designed for program evaluation. Thirty-nine teachers completed the QACSE-P-SF, regarding 657 students (fourth to ninth grades). Factor analyses supported a six-factor structure with acceptable internal consistency. Sex differences were found with teachers reporting girls as having higher scores on Self-Control, Social Awareness, Relationship Skills, and Responsible Decision Making. Developmental differences were also found with fourth-grade students presenting higher levels of Social Awareness and Relationship Skills than older students. The final version of the QACSE-P-SF is composed by 30 items, organized into six scales and less time consuming than the previous version for teachers who need to assess full classes., (© The Author(s) 2016.)

This study investigated the impact, reported by students and their teachers, of a universal, school-based, social-emotional learning program, implemented in three school years on the social-emotional competencies of middle school students (7th to 9th grade). It also analyzes, at post-test and follow-up, the differential results by gender and among students with lower levels of competence. There were 1091 participants, 855 students received the treatment condition (i.e., Project Attitude) and 236 students the control condition. Self-reports identified positive intervention results in social awareness, self-control, self-esteem, social isolation and social anxiety, teachers reported gains in all dimensions. These positive effects were stably effective along the three cohorts. Self-reports also identified bigger gains for girls in social awareness and for boys in social anxiety, self-esteem and leadership. Students with initial lower levels of competence benefited more from the intervention, especially at follow-up. These results support the effectiveness of social-emotional learning programs., (Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)