The Kyoto Collection of Human Embryos and Fetuses: History and Recent Advancements in Modern Methods.

The Kyoto Collection of Human Embryos and Fetuses, the largest collection of human embryos worldwide, was initiated in the 1960s, and the Congenital Anomaly Research Center of Kyoto University was established in 1975 for long-term storage of the collection and for the promotion of research into human embryonic and fetal development. Currently, the Kyoto Collection comprises approximately 45,000 specimens of human embryonic or fetal development and is renowned for the following unique characteristics: (1) the collection is considered to represent the total population of fetal specimens nationwide in Japan, (2) it comprises a large number of specimens with a variety of external malformations, and (3) for most specimens there are clinical and epidemiological data from the mothers and the pregnancies concerned. Therefore, the specimens have been used extensively for morphological studies and could potentially be used for epidemiological analysis. Recently, several new approaches such as DNA extraction from formalin-fixed specimens or geometric morphometrics have been adopted and it is to be expected that further technological advances will facilitate new studies on the specimens of the Kyoto Collection as well as of other human embryo collections worldwide. Permanent preservation of the Kyoto Collection is, therefore, of paramount importance so that it will continue to contribute to human embryological studies in the future.

Suberoylanilide hydroxamic acid, a novel histone deacetylase inhibitor, improves the development and acetylation level of miniature porcine handmade cloning embryos.

Histone deacetylase inhibitors (HDACis) can change the histone acetylation and significantly enhance the developmental competence of the pre-implantation SCNT embryo. To select a proper histone deacetylase inhibitor to improve the success rate and potentially developmental ability of handmade cloning (HMC) embryos of miniature porcine, we compared the effect of two histone deacetylase inhibitors (SAHA vs. VPA) on HMC embryo development, their histone acetylation level and the expression level of relevant genes. The blastocyst rate and number of blastocyst cells of HMC embryos treated with SAHA (SAHA-HMC) or VPA (VPA-HMC) were significantly higher than those of control (Control-HMC), respectively, but there were no significant difference between SAHA-HMC and VPA-HMC groups. In addition, the acetylation level (AcH4K8) of Control-HMC and VPA-HMC embryos at the blastocyst stage, respectively, was significantly lower than that of in vitro fertilized (IVF) and SAHA-HMC embryos. However, the acetylation H4K8 of the blastocysts had no significant difference between SAHA-HMC and the IVF groups. The SAHA-HMC blastocysts indicated comparative expression levels of Oct4 and HDAC1 (histone deacetyltransferase gene) with those of IVF blastocysts. In contrast, the expression levels of Oct4 were lower and those of HDAC1 were higher in the VPA-HMC and Control-HMC blastocysts, respectively, compared to those of the IVF blastocysts. Our results demonstrated that the HMC embryos treated by SAHA could promote the pre-implantation development and increase the levels of histone H4K8 acetylation and the expression of the OCT4 gene, yet decrease the expression of the HDAC1 gene to the comparable level of the IVF embryos. Our results proved that SAHA may be a better histone deacetylase inhibitor for porcine HMC compared to VPA, and furthermore, it may indicate that SAHA can effectively correct the abnormal histone acetylation during the HMC embryo development and subsequently improve the full-term developmental potential of the HMC embryos after embryo transplantation.

Embryo/Fetus Doses from 18F-Fludeoxyglucose Radiopharmaceutical in Positron Emission Tomography/ Computed Tomography.

Aim: The embryo/fetus may be accidentally exposed to ionizing radiation. The aim of this study is to calculate embryo/fetus doses in pregnant women who underwent F-18 fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan. Materials and Methods: Between June 2015 and June 2021, 15 pregnant women underwent F-18 FDG PET/CT applied to the Genetic Research Center (GETAM). The OLINDA/EXM package program was used for internal radiation dosimetry according to the Medical Internal Radiation Dose scheme. FetDose V4 computer software was used to compute the embryo/fetus absorbed dose from CT scan. Results: The amount of the injected F-18 FDG activity to patients varied between 333 and 555 MBq. The mean embryo/fetal dose from F-18 FDG was 7.2 ± 2.8 mGy. In addition, the CT component dose to the embryo/fetus dose ranged from 8.5 to 16 mGy with a mean of 12.14 ± 2.05. Conclusions: The embryo/fetus dose from F-18 FDG PET/CT was <15 mGy, however, questioning the women's childbearing prior to scintigraphy is the first-line strategy to avoid accidental radiation exposure and stochastic risks.

Exploring polyamines: Functions in embryo/fetal development.

Polyamines such as putrescine, spermidine, spermine and agmatine are aliphatic polycationic compounds present in all living cells, and are derived from amino acids, intestinal bacteria, exfoliated enterocytes and supported from diet. Polyamines as the key compounds play essential role in cell proliferation, growth and differentiation. They also exert significant effects on embryonic development, implantation, embryonic diapause, placentation, angiogensis and fetal development. This review paper summarizes the functions of polyamines and embryo/fetus development and its regulatory mechanism which should help to provide some evidences for clinic.

Mechanisms of Glucocorticoid Action During Development.

Glucocorticoids are primary stress hormones produced by the adrenal cortex. The concentration of serum glucocorticoids in the fetus is low throughout most of gestation but surge in the weeks prior to birth. While their most well-known function is to stimulate differentiation and functional development of the lungs, glucocorticoids also play crucial roles in the development of several other organ systems. Mothers at risk of preterm delivery are administered glucocorticoids to accelerate fetal lung development and prevent respiratory distress. Conversely, excessive glucocorticoid signaling is detrimental for fetal development; slowing fetal and placental growth and programming the individual for disease later in adult life. This review explores the mechanisms that control glucocorticoid signaling during pregnancy and provides an overview of the impact of glucocorticoid signaling on fetal development.

Background data on embryo-fetal development toxicity studies in SD rats / 中国药理学与毒理学杂志

OBJECTIVE: To establish the background data on SD rat embryo-fetal development toxicity studies by Shanghai Institute of Planned Parenthood Research (National Evaluation Center for Toxicology of Fertility Regulating Drugs), and provide reference for reproductive toxicology research. METHODS: From the embryonic-fetal developmental toxicity tests of SD rats between 2010 and 2018, the index data on embryo development and fetal growth and development of pregnant rats was selected, including pregnancy body mass and pregnancy outcomes (average of corpora lutea, implantation, live fetuses, absorptions and dead fetuses), the growth and development of fetuses (fetal body mass, body length and tail length) and fetal appearance, viscera, and skeleton. The data was statistically analyzed, and the mean, standard deviation and coefficient of variation were calculated. RESULTS: Totally 217 pregnant rats and 2506 fetuses were included. The body mass of pregnant rats on gestation day 0 (GD0) was (222±22) g, while the food consumption of GD0-1was (18.9±3.8) g·d-1. The body mass of GD20 was (353±30) g and the food consumption of GD19-20was (26.2±4.0) g·d-1. GD20euthanasia cesarean section examination showed that the pregnancy rate was 95.2%, and that the average of corpora lutea, implantation and live fetuses was 12.8±2.1, 11.8±2.8 and 11.5±2.8, respectively. The rate of live fetuses and absorption rate was 97.9% and 2.1%, respectively. Among the fetal development indexes, the body mass and placental mass were 3.6±0.3 and (0.5±0.1) g, respectively. The body length was (35.7±1.5) mm, the tail length was (12.9±0.4) mm, and the sexual ratio (male/female) was 1.0 (1227/1279). The external, visceral and skeletal variations were 0.2%, 0.5% and 7.4%, respectively. CONCLUSION: The background data on embryo-fetal toxicity studies of SD rats has been established, which can provide reference for reproductive toxicity research.

Historical control data on embryo-fetal development toxicity studies in rabbits / 中国药理学与毒理学杂志

OBJECTIVE To summarize the data on embryo-fetal developmental toxicity study of rabbits, and to establish the background data so as to provide reference for drug reproductive toxicology research. METHODS From the embryo-fetus developmental toxicity study of rabbits in our laboratory between 2011 and 2018, all the data on control groups was selected, including rabbits' pregnancy mass, outcomes of pregnancy (the average number of corpus lutea, implantation, live fetuses, fetal absorption rate, fetal live rate, fetal absorption rate), fetal growth and development (mass, crown-rump length and tail length) and fetal variation (appearance, viscera and skeleton). The mean and standard deviations of each index were calculated. RESULTS The embryo-fetal development indexes of 149 pregnant rabbits and 1097 fetuses were summarized. The gestational age of rabbits was about 3-5 months, and the body mass was (3.0±0.3) kg on gestation day 0 (GD0), and (3.5±0.4) kg on GD28. These rabbits were euthanized and cesarean section examination showed that the pregnancy rate was 85.6%, the average of corpus lutea number was 8.0±2.1, the average number of implantations was 7.6±2.1, the average number of live fetuses was 7.4±2.1, the live rate was 96.2%, the absorption rate was 1.9%, and the death rate was 1.8%. Among the fetal development indicators, fetal body mass was (33.4±5.0) g, placental weight was (4.0±0.8) g, crown-rump length was (86.3±5.9) mm, tail length was (11.3±0.8) mm, and sex ratio (male/female) was 1.0 (550/547). The rate of appearance variation (or malformation) was 0.18%, skeleton variation (or malformation) was 33.5%, and visceral variation (or malformation) was 0.09%. CONCLUSION The background data of the embryo-fetal developmental toxicity study of rabbits is established in our laboratory. The changes of each index are stable, and the spontaneous deformity rate of fetuses is low.