Abstract. Adiponectin is an adipocyte-derived hormone involved in glucose, lipid and energy metabolism. A low plasma adiponectin concentration is associated with insulin resistance, obesity and atherosclerosis. In women, energy homeostasis is remarkably changed during gestation and lactation in order to supply sufficient nutrition for a fetus or newborn. In this study we aimed to elucidate the physiological impact of gestation and lactation on the plasma adiponectin levels and the influence of reproduction-related hormones on adiponectin secretion. We studied the longitudinal changes in plasma adiponectin concentration during pregnancy (1st, 2nd and 3rd trimester) and lactation (3 days and 1 month after the delivery) in lean healthy women (n = 22). The plasma adiponectin level declined slightly as the pregnancy advanced and reached its lowest level during lactation (12.25 ± 0.182 µg/ml at early pregnancy vs. 6.88 ± 0.375 µg/ml at 3 days postpartum, p<0.001). In order to investigate the role of the lactogenic hormone prolactin in the decrease of plasma adiponectin levels during lactation, we further performed in vitro experiments using human primary cultured adipocytes. Western blotting of the adipocyte lysate and ELISA of the culture medium revealed that exogenous prolactin inhibited both production and secretion of adiponectin in a dose-dependent manner. Our results thus suggests that prolactin affects the regulation of maternal metabolism through suppression of adiponectin. DURING pregnancy and lactation, the maternal metabolism is dynamically altered in order to provide adequate nutrition to the fetus and newborn. Gestational insulin resistance appears from mid-pregnancy, and this facilitates efforts to supply energy substrate to the fetus, which preferentially uses glucose as an energy source [1]. For some women, this physiological change results in the development of gestational diabetes mellitus, one of the most problematic complications of pregnancy. While the gestational glucose intolerance rapidly improves after the delivery, maternal carbohydrate and energy metabolism remains altered during lactation in order to satisfy the glucose demand in milk synthesis [2][3][4][5]. Although these physiological alterations in glucose and energy metabolism during pregnancy and lactation have been well recognized, the mechanisms underlying this phenomenon are not fully understood.Adiponectin is an adipocytokine that is predominantly produced by adipocytes and secreted into plasma at high levels. This 30 KDa peptide hormone possesses insulin-sensitizing, antiatherogenic properties and its plasma level inversely correlates with obesity [6][7][8][9][10]. Most recently, Qi et al. reported that intracerebroventricular administration of adiponectin stimulated energy expenditure in mice, suggesting that adiponectin acts on the central nervous system to regulate energy metabolism [11]. Because adiponectin has a variety of effects on glucose and energy metabolism, it is reasonable to hypothesize that adiponectin plays a

Objective: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk.Methods: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000.Results: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994–1999 was reduced to 0.56–0.70, however, the rate in those born in 2000–2003 was 0.98–1.0, almost the same risk as before introduction of the vaccine.Discussion: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.

Combining bevacizumab with chemotherapy was tolerable and efficacy was acceptable in Japanese patients with advanced epithelial ovarian cancer. Bevacizumab seems to reduce platinum-resistant recurrence and is promising for clear cell carcinoma.

Ovarian clear cell adenocarcinoma (CCC) is the second most common subtype of ovarian cancer after high-grade serous adenocarcinomas. CCC tends to develop resistance to the standard platinum-based chemotherapy, and has a poor prognosis when diagnosed in advanced stages. The ANXA4 gene, along with its product, a Ca++-binding annexin A4 (ANXA4) protein, has been identified as the CCC signature gene. We reported two subtypes of ANXA4 with different isoelectric points (IEPs) that are upregulated in CCC cell lines. Although several in vitro investigations have shown ANXA4 to be involved in cancer cell proliferation, chemoresistance, and migration, these studies were generally based on its overexpression in cells other than CCC. To elucidate the function of the ANXA4 in CCC cells, we established CCC cell lines whose ANXA4 expressions are stably knocked down. Two parental cells were used: OVTOKO contains almost exclusively an acidic subtype of ANXA4, and OVISE contains predominantly a basic subtype but also a detectable acidic subtype. ANXA4 knockdown (KO) resulted in significant growth retardation and greater sensitivity to carboplatin in OVTOKO cells. ANXA4-KO caused significant loss of migration and invasion capability in OVISE cells, but this effect was not seen in OVTOKO cells. We failed to find the cause of the different IEPs of ANXA4, but confirmed that the two subtypes are found in clinical CCC samples in ratios that vary by patient. Further investigation to clarify the mechanism that produces the subtypes is needed to clarify the function of ANXA4 in CCC, and might allow stratification and improved treatment strategies for patients with CCC.

No abstract

PurposeTo investigate the impact of adenomyosis on the complications and outcomes of pregnancy in Japan.MethodsWe carried out a multicenter retrospective questionnaire survey. A questionnaire regarding pregnancy complications and the outcomes of pregnancy was sent to 725 facilities.ResultsData were obtained on the cases of 272 pregnant women with adenomyosis from 65 facilities. The complications of pregnancy included miscarriage before 12 weeks of pregnancy (14.8%), miscarriage after 12 weeks of pregnancy (9.9%), preterm delivery (24.4%), fetal growth restriction (11.8%), pregnancy‐induced hypertension (9.9%), intrauterine infection (7.3%), and cervical incompetency (5.3%). The rates of pregnancy complications in the three groups classified according to pretreatment for adenomyosis (no pretreatment, medication, surgery) did not differ to a statistically significant extent. The rates of miscarriage (>12 weeks) and cervical incompetency increased according to the size of the adenomyosis. The rates of pregnancy‐induced hypertension and uterine infection in patients with diffuse‐type adenomyosis were higher than that in patients with focal‐type adenomyosis.ConclusionsOur results show that the increased size and diffuse type of adenomyosis are associated with adverse pregnancy outcome. We should be aware of the higher incidence of pregnancy‐induced hypertension and uterine infection in patients with diffuse‐type adenomyosis.

In this study, we compared the long-term effects of neonatal exposure to diethylstilbestrol (DES, 0.0125-50 microg), tamoxifen (TAM, 0.0125-50 microg), and toremifene (TOR, 53 microg) on mammary gland development and differentiation. Allometric growth of the mammary ducts was stimulated by neonatal DES exposure (12.5 microg) and impaired by exposure to TAM (25 microg). Neonatal treatment with high doses of DES resulted in mammary ducts that displayed extensive dilatation and precocious lactogenesis in postpubertal, nulliparous females. Initiation of this precocious differentiation coincided with the absence of corpora lutea, increased levels of serum prolactin (PRL), and the induction of Prl mRNA expression within the mammary glands. Neonatal exposure to 1.25 microg TAM increased alveolar development in postpubertal, nulliparous females similar to that recorded in females treated with low doses of DES. Lower doses of TAM did not affect alveolar development, whereas branching morphogenesis and alveolar development were impaired by higher doses. Increased alveolar development in females exposed to 1.25 microg TAM was associated with elevated serum progesterone (P) and increased alveolar development in response to exogenous P. Taken together, our findings demonstrate that neonatal exposure to both DES and TAM exerts long-lasting effects on the proliferation and differentiation of the mammary glands in female BALB/c, primarily as the result of endocrine disruption.

Supplemental digital content is available in the text.