Developmental arrest of scNT‐derived fetuses by disruption of the developing endometrial gland as a result of impaired trophoblast migration and invasiveness

Abstract

*Somatic cell nuclear transfer (scNT)-derived pig placenta tissues of gestational day 30 displayed avascularization and hypovascularization. Most of the cytotrophoblast-like cells of the developing scNT-derived placenta villi were improperly localized or exhibited impaired migration to their targeting loci. Id-2, Met, MMP-9, and MCM-7 were barely detectable in the cytotrophoblast cells of the scNT-derived placenta villi. Active MMP-2 and MMP-9 expression was significantly down-regulated in the scNT-embryo transferred recipient uteri. scNT clones exhibited a hypermethylated pattern within the pig MMP-9 promoter region and the significance of GC box in the regulation of MMP-9 promoter activity. Marked apoptosis was observed in the developing endometrial gland of scNT-embryo transferred recipient uteri. Collectively, our data strongly indicated that early gestational death of scNT clones is caused, at least in part, by disruption of the developing endometrial gland as a result of impaired trophoblast migration and invasiveness due to the down-regulation of active MMP-9 expression. Developmental Dynamics 240:627-639,

Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma

“…The fractions of non-expressing tumors in our tumor cohort was generally higher (40% BAP1, 50% H3K36me3, 70% PBRM1) compared to those described in several previous studies, which ranged between 10–50% for BAP1 [19], [21], [22], [37], 14–34% for SETD2 [18], [23], and 31–70% for PBRM1 [20], [21], [23], [38], [39]. The use of different scoring criteria, antibodies, immunostaining protocols, numbers and fixation of the tumors included in the analyses as well as large sections versus tissue microarrays may explain some of the discrepancies.…”

Pregnancy and Neonatal Care of SCNT Animals

“…Abnormalities in placental development have been observed as early as day 30 (Whitworth and Prather 2010;Kim et al, 2011). Umbilical cord and/or placental insufficiency were described at birth , with extensive endometrial edema as a major finding (Schmidt et al, 2011) and abnormal expression of imprinted genes (Wei et al, 2010).…”

Cloned pig fetuses exhibit fatty acid deficiency from impaired placental transport

“…Pig somatic cell nuclear transfer (SCNT) has valuable applications in agriculture, biomedicine, and life science (Matsunari & Nagashima, ; Yang & Wu, ). However, SCNT‐derived cloned pig fetuses frequently exhibit aberrant intrauterine development (Ao et al, ; Ao, Li, et al, ; Chae et al, ; Kim et al, ; Ruan et al, ), leading to high stillbirth occurrence (17–32.8%; Ao, Zhao, et al, ; Estrada et al, ; Huan et al, ; Kurome et al, ; Liu et al, ), congenital malformations (29.5–60.0%; Kurome et al, ; Schmidt, Winther, Secher, & Callesen, ), and neonatal mortality (48.0–74.5%; Ao et al, ; Park et al, ; Schmidt et al, ) in newborn cloned piglets. Nevertheless, available information regarding the causes of erroneous intrauterine development of cloned pig fetuses is extremely limited.…”