No abstract

Uteri of pregnant and nonpregnant women contain enzymic activities which inactivate oxytocin. A potent enzyme, which has been partially purified from uterine homogenates, cleaves the prolyl-leucyl peptide bond of oxytocin. This findinig associates for the first time the release of the dipeptide leucylglycinamide with the degradation of neurohypophyseal hormones.

Recently, cultured human adult skin cells were reprogrammed to induced pluripotent stem (iPS) cells, which have characteristics similar to human embryonic stem (hES) cells. Patient-derived iPS cells offer genetic and immunologic advantages for cell and tissue replacement or engineering. The efficiency of generating human iPS cells has been very low; therefore an easily and efficiently reprogrammed cell type is highly desired. Here, we demonstrate that terminally differentiated human amniotic fluid (AF) skin cells provide an accessible source for efficiently generating abundant-induced pluripotent stem (AF-iPS) cells. By induction of pluripotency with the transcription factor quartet (OCT3/4, SOX2, KLF4, and c-MYC) the terminally differentiated, cultured AF skin cells formed iPS colonies approximately twice as fast and yielded nearly a two-hundred percent increase in number, compared to cultured adult skin cells. AF-iPS cells were identical to hES cells for morphological and growth characteristics, antigenic stem cell markers, stem cell gene expression, telomerase activity, in vitro and in vivo differentiation into the three germ layers and for their capacity to form embryoid bodies (EBs) and teratomas. Our findings provide a biological interesting conclusion that these fetal AF cells are more rapidly, easily, and efficiently reprogrammed to pluripotency than neonatal and adult cells. AF-iPS cells may have a "young," more embryonic like epigenetic background, which may facilitate and accelerate pluripotency. The ability to efficiently and rapidly reprogram terminally differentiated AF skin cells and generate induced pluripotent stem cells provides an abundant iPS cell source for various basic studies and a potential for future patient-specific personalized therapies.

The physiologic mechanisms whereby the human endometrium maintains hemostasis during endovascular trophoblast invasion, yet permits menstrual hemorrhage, are unknown. This paradoxical relationship was investigated by evaluating endometrial expression of tissue factor (TF), the primary initiator of hemostasis, and plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of fibrinolysis. We observed increased immunostaining for TF and PAI-1 in sections of decidualized stromal cells from luteal phase and gestational endometrium. To determine whether TF and PAI-1 expression are directly linked to decidualization, both endpoints were monitored in a well described in vitro model of decidualization. Thus, confluent stromal cell cultures were exposed to vehicle control, 10(-8) M estradiol (E2), 10(-8) to 10(-6) M medroxyprogesterone acetate (MPA) or both E2 + MPA for 2-24 days in serum-containing or defined media. The progestin enhanced the content of stromal cell-associated immunoreactive and functionally active TF and PAI-1 released into the medium and elevated levels of stromal cell TF and PAI-1 mRNA. While E2 alone was ineffective, it greatly augmented MPA-enhanced TF and PAI-1 protein and mRNA content. Dose-dependent effects on TF and PAI-1 content were observed between 10(-8) to 10(-6) M MPA +/- E2. Similar results were observed for decidual cells derived from first trimester endometrium and cultured in type 1 collagen gels. Following optimal induction of TF and PAI-1 expression by E2 + MPA in stromal cell cultures, removal of these steroids greatly reduced levels of both TF and PAI-1 protein and mRNA within 4 days. These studies suggest a mechanism whereby endometrial hemostasis is maintained during trophoblast invasion yet reduced at the end of nonfertile cycles to permit menses.

The aim of this retrospetive study was to identify any consistent patterns between ultrasound findings in failed pregnancies and either normal or abnormal karyotypes. The study involved 102 women in whom the diagnosis of early pregnancy failure was made sonographically. The criteria for a failed pregnancy were: a gestational sac with a mean diameter of > 12 mm without a yolk sac; a yolk sac of > 6 mm mean diameter with or without abnormal morphology that ultimately failed to develop an embryonic structure; and an embryo with a crown--rump length (CRL) of > 5 mm without cardiac activity, or the loss of previously identified cardiac activity. All patients underwent elective dilatation and curettage (D & C) and products of conception were sent for karyotyping. Forty-four pregnancies (43%) had abnormal karyotypes. Of these, 33 (75%) were trisomies. The other 11 included four triploidies, one tetraploidy, two with monosomy X, and four others (unbalanced complement, isochromosome, terminal deletion and translocation). Fifty-eight pregnancies (57%) had normal karyotypes, of which 52 were 46,XX and six were 46,XY. The furthest sonographic anatomic landmark achieved did not differ with respect to karyotypic findings. An abnormal yolk sac was found in 10/58 cases (17.2%) with normal karyotypes and 8/44 cases (18.2%) with abnormal karyotypes. There were eight cases of trisomy 16, of which only two manifested an embryonic structure, but neither of which had cardiac activity; the largest was 4 mm. There were four cases of trisomy 22, of which three developed embryos with a CRL of > 10 mm with cardiac activity (11, 11 and 18 mm, respectively). In three cases of mosaicism, embryos developed cardiac activity, and were 9, 19 and 16 mm. Two cases of monosomy X had embryos of 14 and 24 mm. Only one out of five cases with multiple trisomies developed to a point at which any embryonic structure was identifiable on ultrasound examination. The ultrasound appearance of early pregnancy failure in terms of furthest anatomic landmark reached was not significantly different in cases with normal or abnormal karyotype. An abnormally enlarged yolk sac, presumably secondary to hydropic change, is a non-specific finding of failed pregnancy, and did not correlate with karyotypic abnormality (trisomy 22, mosaic, monosomy X) seem to develop further prior to embryonic demise than those with certain others (trisomy 16, multiple trisomies and unusual other variants.