Overexpression of cyclin D3 improves decidualization defects in Hoxa-10(-/-) mice.

Uterine decidualization, a crucial process for implantation, is a tightly regulated process encompassing proliferation, differentiation, and polyploidization of uterine stromal cells. Hoxa (Homeobox A)-10, a homeobox transcription factor, is highly expressed in decidualizing stromal cells. Targeted gene deletion experiments have demonstrated marked infertility resulting from severely compromised decidualization in Hoxa-10(-/-) mice. However, the underlying mechanism by which Hoxa-10 regulates stromal cell differentiation remains poorly understood. Cyclin D3, a G(1) phase cell-cycle regulatory protein involved in stromal cell proliferation and decidualization, is significantly reduced in Hoxa-10(-/-) mice. The expression of cyclin D3 in the pregnant mouse uterus parallels stromal cell decidualization. Here, we show that adenovirus-driven cyclin D3 replacement in Hoxa-10(-/-) mice improves stromal cell decidualization. To address our question of whether cyclin D3 replacement in Hoxa-10(-/-) mice can improve decidualization, both in vitro and in vivo studies were completed after the addition of cyclin D3 or empty (control) viral vectors. Immunostaining demonstrated increased proliferation and decidualization in both in vitro and in vivo studies, and in situ hybridization confirmed increased expression of decidualization markers in vivo. Placentation was demonstrated as well in vivo in the cyclin D3-replaced animals. However, fertility was not restored in Hoxa-10(-/-) mice after d 10 of pregnancy. Finally, we identified several downstream targets of cyclin D3 during decidualization in vitro via proteomics experiments, and these were confirmed using in situ hybridization in vivo. Collectively, these results demonstrate that cyclin D3 expression influences a host of genes involved in decidualization and can improve decidualization in Hoxa-10(-/-) mice.

Lessons learnt from two women with morbidly adherent placentas and a review of literature.

INTRODUCTION: Pathologically adherent placentas occur when there is a defect of the decidua basalis, typically arising from previous caesarean section, resulting in abnormally invasive implantation of the placenta. The depth of placental invasion varies from the superficial (accreta), to transmural and possibly beyond (percreta). CLINICAL PICTURE: We report on 2 cases, one treated "conservatively", the other with a caesarean hysterectomy, both of which led to a safe outcome for both mother and baby. CONCLUSIONS: Management relies on accurate early diagnosis with appropriate perioperative multidisciplinary planning to anticipate and avoid massive obstetric haemorrhage at delivery.

Histological and histochemical changes of the placenta in fetal alcohol syndrome due to maternal administration of acute doses of ethanol in the mouse.

In both clinical and experimental research on the fetal alcohol syndrome (FAS) the possible involvement of the placenta has not been considered. In an attempt to investigate the effects of alcohol on the placenta, single doses of 0.02 ml and 0.03 ml/g body weight of freshly prepared solutions (25%, v/v) of absolute alcohol in saline were administered to MF1 mice on day 8 of gestation. Controls were saline treated or/and pair fed and pair watered. Fetuses and placentas were collected on day 18, weighed individually, observed for malformations and fixed. Paraffin sections of placentas of control and of fetuses with FAS were stained with hematoxylin and eosin, Best's carmine and PAS with and without diastase (saliva). The experimental fetuses and placentas were lighter in weight than the controls. The decidua basalis of placentas of FAS cases were occasionally vacuolated and infiltrated by lymphocytes. The glycogen and mucopolysaccharide content in the basal zone was reduced. In most situations the glycogen cells had degenerated and were replaced by an acidophilic mass. The cytoarchitecture of the labyrinthine zone had been altered. Large cysts filled most parts of the placenta; besides fibrinoid accumulation, extensive vacuolisation was also clearly visible. The overall width of this zone and arborisation of fetal vasculature were also reduced. The consistent association of these placental abnormalities with FAS in this mouse model is suggestive of placental mechanisms in FAS.

Placenta accreta, increta, and percreta. A survey of 40 cases.

Forty patients with placenta accreta, increta, or percreta are presented. Clinical features revealed an average age of 29.5 years and an average parity of 3-2-1. Twenty-five had no antepartum complications. Nine were admitted with silent hemorrhage, of which 6 had a total placenta previa and 1 a low-lying previa. Postpartum hemorrhage occurred in 39% with an associated perinatal mortality of 25% and 1 maternal death. Histopathologic evaluations revealed the predominant factor to be an absent decidua. Etiologic in decidual deficiency was a previous cesarean section (12 patients). Therapy consisted of total abdominal hysterectomy in 38 patients.