The most distinctive feature of oocyte-specific linker histones is the specific timing of their expression during embryonic development. In Xenopus nuclear transfer, somatic linker histones in the donor nucleus are replaced with oocyte-specific linker histone B4, leading to the involvement of oocyte-specific linker histones in nuclear reprogramming. We recently have discovered a mouse oocyte-specific linker histone, named H1foo, and demonstrated its expression pattern in normal preimplantation embryos. The present study was undertaken to determine whether the replacement of somatic linker histones with H1foo occurs during the process of mouse nuclear transfer. H1foo was detected in the donor nucleus soon after transplantation. Thereafter, H1foo was restricted to the chromatin in up to two-cell stage embryos. After fusion of an oocyte with a cell expressing GFP (green fluorescent protein)-tagged somatic linker histone H1c, immediate release of H1c in the donor nucleus was observed. In addition, we used fluorescence recovery after photobleaching (FRAP), and found that H1foo is more mobile than H1c in living cells. The greater mobility of H1foo may contribute to its rapid replacement and decreased stability of the embryonic chromatin structure. These results suggest that rapid replacement of H1c with H1foo may play an important role in nuclear remodeling.

Pancreatic beta cells compensate for changes in whole body insulin sensitivity through an increase in insulin secretion. The relationship between insulin sensitivity and insulin secretion is characterized by a rectangular hyperbolic function, such that the product of the two variables, termed as the disposition index, should yield a constant for a given degree of glucose tolerance [1][2]. Although beta cell dysfunction and insulin resistance may occur independently, the disposition index typically decreases through the progression from normal glucose toler- abstract. The aim of this study is to explore beta cell dysfunction and its clinical significance in gestational diabetes mellitus (GDM). We assessed insulin sensitivity and insulin secretion in a total of 277 Japanese women between 24 and 27 weeks of pregnancy who underwent a 2 h, 75 g oral glucose tolerance test (OGTT) because of an abnormal result on a 1 h 50 g oral glucose challenge conducted as part of a standard screening for GDM. Insulin sensitivity was evaluated by an insulin sensitivity index derived from OGTT (IS OGTT ), whereas insulin secretion was calculated as a ratio of the total area under the insulin curve to the total area under the glucose curve (AUC ins/glu ). Beta cell function in relation to insulin sensitivity (i.e. disposition index) was derived from the product of insulin sensitivity and insulin secretion (i.e. AUC ins/glu × IS OGTT ). In women diagnosed with GDM (n=57), the disposition index was significantly lower than that in those without GDM, irrespective of obesity. The disposition index in women with GDM was significantly correlated with levels of fasting and mean preprandial capillary glucose and HbA1c before initiating insulin therapy (r = -0.45, -0.38, -0.49, respectively). Furthermore, there was a significant correlation between the disposition index and total insulin dosage to achieve glycemic goal (r = -0.41). In conclusion, we demonstrated beta cell dysfunction in Japanese women with GDM irrespective of obesity. The level of beta cell dysfunction in GDM was associated with the severity of glucose intolerance and total insulin dosage required. These findings underpin clinical significance of beta cell dysfunction in GDM.

ObjectiveTo investigate pregnancy outcomes in women after abdominal radical trachelectomy (RT) for early-stage cervical cancer.MethodsThe patients’ background, fertility, and pregnancy outcomes were reviewed in a total of 61 pregnancies in 48 of 172 women who underwent abdominal RT at Keio University Hospital between September 2002 and December 2013.ResultsThere were 5 women with stage IA1, 2 with stage IA2, and 41 with stage IB1. Histological types were as follows: squamous cell carcinoma (n = 36), adenocarcinoma (n = 10), and adenosquamous cell carcinoma (n = 2). The pregnancy rate of women attempting to conceive after abdominal RT was 44% (48/109). The mean ± SD duration from abdominal RT to conception was 3.1 ± 1.9 years. Of 61 pregnancies, 42 pregnancies were achieved by fertility treatment (in vitro fertilization-embryo transfer, 39; intrauterine insemination, 3). After excluding one pregnancy without detailed clinical information, there were 42 live births (5 in 22–27 weeks, 11 in 28–33weeks, 20 in 34–36 weeks, and 6 in 37–38 weeks), 13 miscarriages, and 5 ongoing pregnancies. While there were 10 first trimester miscarriages, 3 pregnancies ended in the second trimester owing to chorioamnionitis. The mean gestational age at birth was 33 weeks of pregnancy. Thirty-seven neonates were appropriate-for-date, and one was small-for-date. Six pregnancies exhibited massive bleeding from the residual cervix in the late pregnancy. Preterm birth less than 34 weeks of pregnancy was related to premature rupture of the membrane (P < 0.05). Chorioamnionitis was evident in 9 of 11 pregnancies with preterm premature rupture of the membrane followed by birth at less than 34 weeks of pregnancy. No parturients exhibited lochiometra and endometritis postpartum.ConclusionsAbdominal RT provided favorable pregnancy outcomes, and fertility treatment could be advantageous to conception. Massive bleeding from the residual cervix as well as ascending infection might be characteristic features during pregnancy after abdominal RT.

Becausesonography is nowcapable of achieving increased resolution, ovarian tumors are more fre quently found in early pregnancy. In this case, we describea patientin the secondtrimester with ovarian endometriosis, which enlarged and was accompanied by structural changes inside the tumor. Case ReportA 28-year-old primigravidawas first seen in our antenatal clinic at 5 weeks of gestation. She had a history ofovarian endometriosis and had been treated with a gonadotropin-releasing hormone analogue before the pregnancy. A sonographic examination showed an intrauter me gestationsac and a right ovariantumor.The tumor was a unilocular cyst with fine in ternal echoesand a maximum diameter of 45 mm (Fig. 1A). Because the patient had a his tory of endometriosis, the tumorwasbelieved to represent an endometrial cyst and was treated conservatively.At 16 weeks ofgestation, sonographic exam ination revealeda fetus appropriatefor the ges tational age and showed an increase in size of the ovariancyst, which had reacheda maximum diameter of 85 mm. On transvaginalsonogra phy, irregularhyperechogenicrepresentingpap illary excrescences structures were seen inside the cyst. Color-flow Doppler sonography de picted vascularity within the solid irregular ar eas (Fig. 1B). These sonographic changes became more remarkable at i8 weeks of gesta flon. For further evaluation of a possible malig nancy, MR imaging was performed.The high signalintensityon TI-andT2-weightedimages was in the cystic portion of the tumor, suggest ing blood products. The solid portion was dark on Tl-weighted images and bright on 12-weighted images, suggesting malignancy that may have arisenfrom the endometriosis (Figs. lCand lD).On exploratory laparotomy performed at 20 weeksof gestation,a right ovariantumor adher ingtotheposterior wall ofthe uteruswasfound. A smallamountof asciteswasalsonoted.The tumor, which contained chocolatelike bloody fluid,hadalreadyraptured. After suctioning the fluid from the tumor, a right salpingo-oophorec tomy was performed.Papillaryexcrescences werefoundprotruding intothelumenof thetu mor. Final histopathologicexamination re vealed ovarian endometnosis with marked decidual changes and hemorrhage and without evidenceof malignancy (Fig. 1E). The patient recovered promptly and delivered a 3704-g healthymale infant at 40 weeksof gestation. during human pregnancy;thus, we did not use this contrast material in our patient. The clinical findings were indicative of malig nancy;however,final histopathologic exami nation of the tumor merely revealed solid tissue representing massive decidualization and hemorrhage. To our knowledge, ovarian endometriosisincreasingin size and accom panied by marked decidual bleeding during pregnancyis a rareoccurrence. The malignant transformation of endometri osis has been well documented, and persistent estrogenic stimulation has been implicated as a cause [4,5]. Becauseof this,ovarianendometri osis in pregnant women should be treated with special attention to structural changes that occur during pregnancy. Disc...

We present a case of congenital midgut volvulus detected by prenatal sonography and ultrafast magnetic resonance (MR) imaging. At 34 weeks of gestation, enlarged hyperechogenic loops without peristalsis was identified by sonographic examination. On ultrafast T2-weighted single-shot fast-spin echo MR imaging, enlarged loops exhibited a lower signal intensity than the surrounding bowel loops, suggesting intraluminal hemorrhage. At explorative laparotomy following delivery, midgut volvulus causing hemorrhagic necrosis was found. Combined use of sonography and ultrafast MR imaging is useful to identify fetal midgut volvulus with hemorrhagic change.

Proteolytic activities are essential for follicular growth, ovulation, as well as for luteal formation and regression. Using suppression subtractive hybridization (SSH), a novel mouse ovary-selective gene (termed protease serine 35, Prss35) was identified. Analysis of the mouse genome database using the Prss35 sequence led to the identification of a homologous protease (protease serine 23, Prss23). PRSS35 possesses general features that are characteristic of serine (Ser) proteases, but is unique in that the canonical Ser that defines this enzyme family is replaced by a threonine (Thr). In contrast, PRSS23 possesses the standard catalytic Ser typical for this family of proteases. As determined by real-time polymerase chain reaction (PCR), the Prss35 mRNA levels increased around the time of ovulation and remained elevated in the developing corpus luteum. Steroid ablation/replacement studies demonstrated progesterone-dependent regulation of Prss35 gene expression prior to follicle rupture. Prss35 gene expression was localized to the theca cells of pre-antral follicles, the theca and granulosa cells of pre-ovulatory and ovulatory follicles, as well as to the developing corpus luteum. In contrast, Prss23 mRNA levels decreased transiently after ovulation induction and again in the postovulatory period. Prss23 gene expression was noted primarily in the granulosa cells of the secondary/early antral follicles. PRSS35 and PRSS23 orthologs in the rat, human, rhesus macaque, chimpanzee, cattle, dog, and chicken were identified and found to be highly homologous to one another (75-99% homology). Collectively, these results suggest that the PRSS35 and PRSS23 genes have been conserved as critical ovarian proteases throughout the course of vertebrate evolution.

Prospective multicenter studies are needed to determine if the results shown in this retrospective cohort can be generalized to all patients with early-stage cervical cancer who wish to undergo the fertility-sparing RAT procedure.

We report a family in which a healthy, unrelated couple had a male fetus with bilateral ventriculomegaly, a normal liveborn girl, a hydatidiform molar pregnancy, a female fetus with ventriculomegaly and situs abnormalities, and a male fetus with hydrocephalus, a three-lobed left lung, and defective tracheal cilia with absent inner dynein arms and a single centriole. A mutation analysis of FOXJ1 and POLL in the last fetus with ciliary defect revealed no mutation within their coding regions. The presence of three affected fetuses of both sexes in a family with phenotypically normal parents suggests that the condition was inherited as an autosomal recessive trait. A thorough evaluation of the thoracic and abdominal situs is recommended before counseling a family of a child with hydrocephalus, because the recognition of situs defects may point to the diagnosis of primary ciliary defect and recurrence risk of 25% for siblings. This figure is much higher than the general risk of 1-2% for siblings of a patient with isolated hydrocephalus.