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These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian tissue transplanted, and two women underwent fresh ovarian tissue transplants. The function of ovarian cortical strips has continued for more than 7 years in these three women, with the birth of eight healthy babies following a single graft per patient. In addition to these three cases, transplantation (repeatedly in some cases) of cryopreserved ovarian tissue has restored reproductive function to all other women in the study centres' programmes for some years. The sustained longevity of function of the transplanted tissue suggests that it may also be possible to postpone the normal time of menopause or to alleviate its symptoms., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Over the first 4 days of their life, primordial germ cells invade the endoderm, migrate into and through the developing hindgut, and traverse to the genital ridge where they cluster and ultimately inhabit the nascent gonad. Specific signal-receptor combinations between primordial germ cells and their immediate environment establish successful migration and colonization. Here we demonstrate that disruption of a cluster of six genes on murine chromosome 8, as exemplified by the Fused Toes (Ft) mutant mouse model, results in severely decreased numbers of primordial germ cells within the early gonad. Primordial germ cell migration appeared normal within Ft mutant embryos; however, germ cell counts progressively decreased during this time. Although no difference in apoptosis was detected, we report a critical decrease in primordial germ cell proliferation by E12.5. The six genes within the Ft locus include the IrxB cluster (Irx3, -5, -6), Fts, Ftm, and Fto, of which only Ftm, Fto, and Fts are expressed in primordial germ cells of the early gonad. From these studies, we have discovered that the Ft locus on mouse chromosome 8 is associated with cell cycle deficits within the primordial germ cell population that initiates just before translocation into the genital ridge., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Proper cell fate determination in mammalian gonads is critical for the establishment of sexual identity. The Hedgehog (Hh) pathway has been implicated in cell fate decision for various organs, including gonads. Desert Hedgehog (Dhh), one of the three mammalian Hh genes, has been implicated with other genes in the establishment of mouse fetal Leydig cells. To investigate whether Hh alone is sufficient to induce fetal Leydig cell differentiation, we ectopically activated the Hh pathway in Steroidogenic factor 1 (SF1)-positive somatic cell precursors of fetal ovaries. Hh activation transformed SF1-positive somatic ovarian cells into functional fetal Leydig cells. These ectopic fetal Leydig cells produced androgens and insulin-like growth factor 3 (INLS3) that cause virilization of female embryos and ovarian descent. However, the female reproductive system remained intact, indicating a typical example of female pseudohermaphroditism. The appearance of fetal Leydig cells was a direct consequence of Hh activation as evident by the absence of other testicular components in the affected ovary. This study provides not only insights into mechanisms of cell lineage specification in gonads, but also a model to understand defects in sexual differentiation.

Irx3 is a member of the Iroquois homeobox gene family that encodes a protein known for its essential role in spinal cord development. Transcript screening of male and female gonads during the critical period of sex determination (E12-13.5) revealed a sexually dimorphic expression pattern for Irx3 with female gonads exhibiting a sixfold increase in expression over time. Whole mount in situ hybridization confirmed the sexually dimorphic nature of Irx3 expression and immunohistochemical analysis of gonads at E13.5 determined that IRX3 and GATA4 proteins co-localized to somatic cells of XX gonads. The Irx3 signal persisted in germ cell-depleted XX gonads resulting from Busulfan treatment suggesting that its expression was independent of germ cell regulation. Quantitative real-time PCR analysis over an extended time course determined that Irx3 message was low initially and then increased in XX gonads until E13.5, remained elevated until birth, diminished shortly after birth, and remained low in the adult ovary. In contrast, Irx3 message was 50% lower in male compared to female gonads at the initial time point, and continued to decrease over time. Further analysis of adult ovaries suggested that IRX3 expression is not present in any subpopulations of cells of the differentiated ovary. Together, these results suggest that the Irx3 signal is restricted to the somatic cell component of XX gonads and is present at a discreet period of ovarian development that ends abruptly at birth. This timing coincides with the transition of female primordial germ cells from mitotic proliferation to meiotic division, and the organization of germ cell cysts prior to primordial follicle development at birth.

Objective: To describe the development and initial evaluation of the Coping Course, a cognitive-behavioral group intervention designed to enhance general coping and problem-solving skills among incarcerated youth., Method: Between 2001 and 2002, 76 male adolescents incarcerated at a youth correctional facility were assessed by questionnaire and randomly assigned to either the Coping Course (n = 46) or usual care (n = 30). Participants repeated the questionnaire after completion of the intervention. A second correctional facility served as an additional source of control group data (n = 62)., Results: Significant condition x time effects were present for seven of the examined measures: Youth Self-Report externalizing scores, three measures from the Life Attitudes Scale, self-esteem, one measure of social adjustment, and cognitive-behavioral therapy knowledge. Age and race/ethnicity did not moderate effects. Comparing control group participants with youth at a separate correctional facility who did not receive the Coping Course indicated that change was uniquely associated with participation in the intervention., Conclusions: Our goal was to take an efficacious adolescent depression group intervention and modify it for use with youth in correctional facilities. Preliminary findings are promising and provide evidence for future research of cognitive-behavioral group treatments with incarcerated youth.

Objective: To evaluate effectiveness of the Adolescent Coping With Depression (CWD-A) course, a cognitive-behavioral group intervention for depressed adolescents with comorbid conduct disorder., Method: Between 1998 and 2001, 93 nonincarcerated adolescents (ages 13-17 years) meeting criteria for major depressive disorder and conduct disorder were recruited from a county juvenile justice department and randomly assigned to the CWD-A or a life skills/tutoring control condition. Participants were assessed post-treatment and at 6- and 12-month follow-up. Dichotomous outcomes were analyzed with logistic regression; dimensional measures were analyzed using random effects regression., Results: Major depressive disorder recovery rates post-treatment were greater in CWD-A (39%) compared with life skills/tutoring control (19%) (odds ratio 2.66, 95% confidence interval = 1.03-6.85). CWD-A participants reported greater reductions in Beck Depression Inventory-II (r2 = 0.055, p =.033) and Hamilton Depression Rating Scale (r2 = 0.047, p =.039) scores and improved social functioning (r2 = 0.064, p =.019) post-treatment. Group differences in major depressive disorder recovery rates at 6- and 12-month follow-up were nonsignificant, as were differences in conduct disorder both post-treatment and during follow-up., Conclusions: This is the first randomized, controlled trial of a psychosocial intervention with adolescents with major depressive disorder and conduct disorder. Although the CWD-A appears to be an effective acute treatment for depression in adolescents with multiple disorders, findings emphasize the need to improve long-term outcomes for depressed adolescents with psychiatric comorbidity and imply that interventions for comorbid populations focus directly on each specific disorder.