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Xenografting of testicular tissue from an infant human donor results in accelerated testicular maturation

Posted: April 14, 2010 at 8:20 am

BACKGROUND

Grafting of testicular tissue into immunodeficient mice has been used to differentiate the neonatal testes from different animal species up to the level of complete spermatogenesis; however, this approach has not been successful for human testicular tissue. The aim of this study was to evaluate the capacity for differentiation of infant human testicular tissue grafts.

METHODS AND RESULTS

Testicular tissue from a 3-month-old patient with testicular cancer was grafted into immunodeficient nude mice. At the time of grafting, A spermatogonia were the only germ cells present in the testicular tissue. B spermatogonia and first spermatocytes were observed at 7 months and 1 year after grafting, respectively. Positive immunostaining with antibodies against BOULE and CDC25A suggested that spermatocytes in the graft were not arrested but in meiosis. Furthermore, ultrastructural and immunohistochemical analyses showed that the onset of both Sertoli cell maturation and partial differentiation of Leydig cells preceded the appearance of spermatocytes. Differentiation of testicular cells was accelerated compared with in vivo development.

CONCLUSIONS

Spermatogenesis in the xenograft of infant human testicular tissues proceeded successfully from the stage of spermatogonial stem cells until pachytene spermatocyte formation. The differentiation of Sertoli cells and Leydig cells was reproduced in a manner similar to that in normal testicular development. Grafting of infant human testicular tissue may be a powerful tool to examine the early period of human spermatogenesis and may pave the way for fertility preservation among infant patients.

Recommendation and review posted by Guinevere Smith

Karyotype of miscarriages in relation to maternal weight

Posted: April 14, 2010 at 8:20 am

BACKGROUND

Obesity has been identified as a risk factor for spontaneous miscarriage although the mechanism is unclear. The purpose of this study is to better understand the effect of obesity on early pregnancy success by examining the cytogenetic results of miscarriages in women with normal and elevated body mass index (BMI).

METHODS

We conducted a retrospective case–control study in an academic infertility practice. Medical records of women ages <40 years with first trimester missed abortion (n = 204), who underwent dilatation and curettage between 1999 and 2008, were reviewed for demographics, BMI, diagnosis of polycystic ovary syndrome (PCOS) and karyotype analysis. 2 and Student’s t-test analysis were used for statistical analysis, with P < 0.05 considered significant.

RESULTS

A total of 204 miscarriages were included, from women with a mean age of 34.5 years. The overall rate of aneuploidy was 59%. Women with BMI ≥ 25 kg/m2 had a significant increase in euploid miscarriages compared with women with lower BMI (P = 0.04), despite a similar mean age (34.4 years for both).

CONCLUSIONS

We found a significant increase in normal embryonic karyotypes in the miscarriages of overweight and obese women (BMI ≥ 25). These results suggest that the excess risk of miscarriages in the overweight and obese population is independent of embryonic aneuploidy. Further studies are needed to assess the impact of lifestyle modification, insulin resistance and PCOS on pregnancy outcomes in the overweight and obese population.

Recommendation and review posted by Guinevere Smith

Endoglandular trophoblast, an alternative route of trophoblast invasion? Analysis with novel confrontation co-culture models

Posted: April 14, 2010 at 8:20 am

BACKGROUND

Routes of trophoblast invasion seem to be clear, whereas specific invasive pathways need further elucidation. Extravillous trophoblasts (EVTs) transform spiral arteries to guarantee appropriate blood flow to the placenta in the second trimester. Embryo nutrition during the first trimester is thought to be histiotrophic, whereas proof that EVTs also invade uterine glands is lacking. We developed novel three-dimensional confrontation co-culture models to elucidate invasion of EVTs into uterine glands.

METHODS

First trimester decidua parietalis and placental villous explants were directly confronted and co-cultured for 72 h, or confronted indirectly after 72 h pre-culture for re-epithelialization of decidua pieces. Cryosections were stained by immunohistochemistry or immunofluorescent/immunohistochemical double labelling and compared with first trimester placentation sites in situ.

RESULTS

EVTs deeply invaded decidual tissues in direct confrontation assays and were found between the decidual epithelial cells and epithelial basement membrane. EVTs were also detected in the decidual stroma in direct proximity to glands, sometimes even replacing glandular epithelial cells. Similar observations were made in sections from the first trimester decidua/placental bed. In the invaded parts of sections of decidua basalis, 55% ± 7% (mean ± SEM; n = 10, range 6–11 weeks) of glandular cross sections were associated with or infiltrated by EVTs.

CONCLUSIONS

Using novel confrontation co-culture assays, a potential new route of EVT invasion was detected. EVTs appear to break through the basement membrane of uterine glands to open their lumen towards the intervillous space. These data support the hypothesis of histiotrophic nutrition of the embryo prior to onset of maternal blood flow within the placenta.

Recommendation and review posted by Guinevere Smith

Regulation of extravillous trophoblast invasion by uterine natural killer cells is dependent on gestational age

Posted: April 14, 2010 at 8:20 am

BACKGROUND

Extravillous trophoblast (EVT) cell invasion of uterine decidua and the inner third of myometrium is critical for successful pregnancy. Many decidual factors are likely to play a role in regulating this process. We have previously shown that cytokines, known to be produced by uterine natural killer (uNK) cells, such as TNF-, TGF-β1 and IFN- inhibit EVT invasion. We therefore hypothesized that supernatants from purified uNK cells would inhibit EVT invasion.

METHODS AND RESULTS

Total unfractionated decidual cell supernatants from 8 to 10 weeks gestation increased EVT invasion from placental villous explants, although uNK cell supernatants from 8 to 10 weeks gestation had no effect. In contrast, both total decidual and uNK cell supernatants from 12 to 14 weeks gestation stimulated EVT invasion. MMP-2, uPA, PAI-1 and PAI-2 levels did not differ under any of the conditions tested, whereas MMP-9 levels were increased in the presence of both total decidual and uNK cell supernatants from both gestational age groups. There was a decrease in the level of EVT apoptosis in the presence of uNK cell supernatant from 12 to 14 weeks, but not 8–10 weeks, gestation.

CONCLUSIONS

Decidual uNK cell supernatants from 12 to 14 weeks gestational age stimulated EVT invasion, potentially by increasing MMP9 levels and reducing apoptosis. Total decidual cell isolates stimulated EVT invasion at both gestational ages investigated, potentially reflecting the complex nature of these cell culture supernatants.

Recommendation and review posted by Guinevere Smith

Functional regulation of thymic stromal lymphopoietin on proliferation and invasion of trophoblasts in human first-trimester pregnancy

Posted: April 14, 2010 at 8:20 am

BACKGROUND

Thymic stromal lymphopoietin (TSLP) is a novel cytokine that triggers the dendritic cell-mediated TH2 response and regulatory T cell expansion. The aim of this study is to evaluate whether TSLP and TSLP receptor (TSLPR) are expressed in primary human extravillous trophoblast (EVT), how proimflammatory cytokines (tumor necrosis factor (TNF)-, IL-1β), TH2 and TH3 cytokines (IL-4, TGF-β) and pregnancy-associated hormones regulate TSLP production by EVT and whether the SLP–TSLPR interaction affects the biological behavior of trophoblsts.

METHODS

We assessed TSLP mRNA and protein expression by real-time RT–PCR, ELISA and immunochemistry, respectively. We further investigated effects of TSLP on the proliferation and invasion of trophoblast cells in vitro.

RESULTS

The primary EVTs constitutively expressed TSLP and TSLPR. IL-4 and TNF- or pregnancy-associated hormones result in a significant increase in TSLP mRNA expression and protein release from EVT, and TSLP promotes primary EVT proliferation and invasion in vitro.

CONCLUSIONS

This study has demonstrated that the first-trimester human trophoblast cells express TSLP and TSLPR, that cytokine milieu which mimics the maternal–fetal interface modulates expression of TSLP in trophoblast and that TSLP stimulates trophoblast proliferation and invasion. This suggests that TSLP plays an important role in human EVT invasion and placentation in human early pregnancy.

Recommendation and review posted by Guinevere Smith

Home self-administration of vaginal misoprostol for medical abortion at 50-63 days compared with gestation of below 50 days

Posted: April 14, 2010 at 8:20 am

BACKGROUND

Home use of misoprostol for termination of pregnancy is still controversial in many countries. Acceptability of home use of misoprostol has been investigated in pregnancies below 49 days gestation. In this study, we aimed to assess efficacy, feasibility and acceptability of home use of vaginal misoprostol for medical termination of pregnancy at 50–63 days compared with gestation of below 50 days among women who chose to administer misoprostol at home.

METHODS

In this prospective study, mifepristone 200 mg was given in hospital under nursing supervision in the university hospital outpatient family planning clinic. Women self-administered misoprostol 800 µg vaginally 36–48 h later at home. Follow-up was 2 weeks later. Women with gestation of 50–63 days on the day of mifepristone administration were compared with women with gestation of below 50 days. Efficacy and feasibility were assessed by review of patient records and questionnaires. Acceptability was assessed using questionnaires where women reported on future choice of abortion method were they to have another abortion.

RESULTS

Among the 2992 women who had a medical abortion during the study period, 395 women chose to administer misoprostol at home and were included in the study. A total of 203 women were below 50 days gestation and 192 were between 50 and 63 days gestation. Efficacy was 97.5% and did not differ between the groups. Surgical intervention was needed in 10 patients, of whom four were in the lower gestational band (P = 0.36). No serious adverse events or blood transfusions were reported. Preference for home administration of misoprostol, were they to have another induced abortion in the future, was high, 92.3 and 86.6% respectively, and did not differ between the groups (P = 0.097). Need for extra analgesia significantly influenced women’s experiences in both gestational groups.

CONCLUSIONS

Medical abortion with mifepristone followed by home administration of vaginal misoprostol is safe and highly acceptable also to women with gestational length of 50–63 days as compared with shorter gestations. Efficacy, acceptability and preference for future place of administration of misoprostol, were women to have another abortion, did not differ between women with gestation below 50 days or between 50 and 63 days.

Recommendation and review posted by Guinevere Smith


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