Synergistic role of nitric oxide and progesterone during the establishment of pregnancy in the rat

Successful pregnancy is strictly dependent on the trophoblast-decidual interaction and on an adequate blood supply to the implantation sites. Nitric oxide (NO) has been shown to play an important role during advanced gestation, although its role during early pregnancy is unclear. The aim of the present study in rats was to evaluate whether NO plays a role during the preimplantation [days 1-4 post coitum (p.c.)] and peri-implantation (days 6-8 p.c.) phases of pregnancy. The rats were treated with the non-specific nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME), and the iNOS inhibitor aminoguanidine in the presence and absence of low-dose antiprogestin, onapristone, and evaluated on days 9 p.c. and 19 p.c., respectively. Before implantation, the treatments alone (L-NAME, aminoguanidine, onapristone) had little effect on pregnancy outcome. Conversely, aminoguanidine plus onapristone treatment completely prevented pregnancy, whereas L-NAME plus onapristone reduced the pregnancy rate to approximately 50%. In addition, both treatments drastically reduced decidualization. Oviductal flushing experiments revealed arrest of embryo development at around the 8-cell stage after aminoguanidine plus onapristone treatment on days 1-4 p.c. Similarly, treatment during the peri-implantation period with L-NAME, aminoguanidine, and onapristone each had only marginal effects on pregnancy. However, a combination of L-NAME and onapristone, and aminoguanidine plus onapristone prevented pregnancy in 71% and 42% of dams, respectively, as determined on day 19 p.c. These treatments also markedly inhibited the decidualization process. This study demonstrates synergistic effects of NOS inhibitors and an antiprogestin in preventing pregnancy. NOS, particularly the cytokine- and progesterone-inducible iNOS, may represent a new target for novel therapeutic agents capable of promoting or inhibiting pregnancy.     

The effect of a levonorgestrel-releasing intrauterine device on human endometrial oestrogen and progesterone receptors after one year of use

Thirty-four women bearing a levonorgestrel-releasing intrauterine device, 20 micrograms/day (LNG-IUD-20), for 12-15 months were recruited. Endometrial biopsies were collected during the late proliferative phase of the cycle (on cycle days 10-12) before (control) and after the use of the IUD for 12 months, and assayed for oestrogen receptors (ER) and progesterone receptors (PR). An immunohistochemical technique with the peroxidase-antiperoxidase detection system (PAP method) was employed. D75 and JZB39 were the primary antibodies for ER and PR respectively. The immunostaining semiquantitative analysis was performed with a computerized microscope image processor, and expressed as 'grey value'. Both endometrial ER and PR populations were significantly lower after insertion of the IUD (P < 0.01) than in control biopsies. The intensity of nuclear staining and the percentage of positively stained cells for ER and PR in women with LNG-IUD were each about 50% of those in control biopsies. The results suggested that LNG released locally from the IUD has a depressive action on the ER and PR, which may contribute to the contraceptive effectiveness of this type of IUD and also to the possible causes of LNG-IUD-induced irregular bleeding and amenorrhoea.     

Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating TFH/B cell axis

Circulating T_FH (cT_FH) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-γ, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cT_FH1, cT_FH2, cT_FH17, and cT_FR cells, respectively. This CD4⁺T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cT_FH cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-β-estradiol (E2) directly increased the percentage of different cT_FH subsets. While E2 and progesterone (P4) increased the proportion of differentiated T_FH cells derived from naïve CD4⁺T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/T_FH cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10⁺T_FR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cT_FH and B cell subsets.     

Pregnancy and sex steroid hormones enhance circulating calcitonin gene-related peptide concentrations in rats

Calcitonin-gene-related peptide (CGRP) is a 37 amino acid neuropeptide synthesized primarily in dorsal root ganglia (DRG) and distributed widely in the perivascular nerves, suggesting that this peptide may play a role in the regulation of peripheral vascular tone. Since female sex steroid hormones have been implicated in the regulation of peripheral vascular tone during pregnancy, we postulated that they may alter the concentration of CGRP in the circulation and thus modulate the increased blood flow observed during pregnancy. In the present study, we measured changes in plasma concentrations of CGRP in non-pregnant, pregnant, and post-partum rats. Groups of ovariectomized rats were treated s.c. for 3 days either with 17beta-oestradiol (2.5 microg per injection twice daily), progesterone (2 mg per injection twice daily), or vehicle. Another group of adult, non-pregnant rats at dioestrus stage of the oestrous cycle was also used in this study. Plasma concentrations of CGRP were higher (P < 0.05) in rats on day 19 of pregnancy (22.0 +/- 3.0 pmol/l) compared to that during delivery (5. 0 +/- 2.0), post-partum day 2 (2.0 +/- 0.7) or in non-pregnant (4.9 +/- 1.6) state. Furthermore, in adult ovariectomized (6.0 +/- 0.6) rats, plasma CGRP concentrations were increased significantly (P < 0. 05) by oestradiol (10.0 +/- 1.0), progesterone (9.5 +/- 1.0) and oestradiol + progesterone (14.0 +/- 1.0). Thus, circulating concentrations of CGRP are elevated during pregnancy and by oestrogen and progesterone, suggesting that the elevated concentrations of CGRP may play an important role in vascular adaptations that occur during pregnancy.     

Recombinant follicle stimulating hormone in in-vitro fertilization treatment-clinical experience with follitropin alpha and follitropin beta

The objective of this prospective study was to compare the outcome of ovarian hyperstimulation for in-vitro fertilization (IVF) using two different preparations of recombinant follicle stimulating hormone (FSH). The study was based on 296 consecutive IVF cycles in 1997, 199 performed using follitropin alpha (Gonal-F) and 97 performed using follitropin beta (Puregon). Outcome was compared regarding pregnancy rate, oestradiol and progesterone response, endometrial thickness, follicle number, number of retrieved oocytes, fertilized oocytes, sperm count and sperm motility. There was no significant difference in outcome of stimulation. Clinical pregnancy rate was similar, 29.1% for Gonal-F and 28.1% for Puregon. There was no difference in endometrial response, oestradiol response, number of smaller (12-15 mm) or larger (>15 mm) follicles, number of oocytes retrieved, fertilized, divided and replaced, in sperm counts or in sperm progressive motility. There was a lower follicle number in the Puregon group, but not statistically significant. The serum progesterone concentrations on the day of oocyte retrieval, however, were significantly lower in the Puregon group. In conclusion, it was not possible to find significant differences in the IVF programme with regard to stimulation outcome between Gonal-F and Puregon. The results of this study indicate that Gonal-F and Puregon may be equally suitable for use in ovarian stimulation for IVF.     

Effects of various medicinal forms of progesterone on lipid peroxidation and glutathione redox system in skin tissues of rats with experimental dermatitis

Activity of glutathione redox system in the dermis and epidermis decreased and the intensity of lipid peroxidation increased in rats with experimental dermatitis. Progesterone normalized these parameters. The most optimal treatment was subcutaneous injections of the hormone in a dose of 7×10⁻⁹ mol/100g. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 2, pp. 186–188, February, 2000     

Cystic tumors of the liver: on the problems of diagnostic criteria

We report on three cases of cystic neoplasms of the liver with mucinous epithelium. Case 1 showed a low-grade cystic neoplasm with ovarian-like stroma (OS). Case 2 showed a low-grade cystic neoplasm without OS, and case 3 showed a high-grade cystic neoplasm without OS. In all three cases, bile duct communication (BDC) was absent. Currently, pancreatic mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm of the pancreas (IPMN) are clearly distinguishable. However, MCN of the liver and intraductal papillary neoplasm of the bile duct (IPN-B) are not as easily distinguished. According to the latest WHO classification (2010), these conditions are classed as typical MCN of the liver, MCNs of the liver without OS, or IPN-Bs without BDC. The clinicopathological differences between MCN without OS and IPN-B without BDC are controversial. We present three cases describing these presentations and discuss the difficulties related to the diagnostic criteria used to distinguish between MCN of the liver and IPN-B.     

Neudesin: a neuropeptide hormone decreased in subjects with polycystic ovary syndrome

Abstract

Neudesin is a neuropeptide hormone involves in female reproduction system via promoting effects of progesterone. Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disorder associated with hypothalamic-pituitary-ovarian axis abnormalities and impaired negative feedback mechanism of progesterone upon gonadotropin-releasing hormone secretion. Our aims were to discover whether neudesin levels were altered in PCOS women comparing to controls and to determine the link of neudesin with hormonal-metabolic parameters in PCOS women. The current research was designed as a case-control study. Sixty-eight subjects with PCOS and 67 age- and body mass index (BMI)-matched subjects as controls were enrolled into the study. Circulating neudesin levels were measured by ELISA. Neudesin levels were significantly lower in PCOS subjects compared to controls (4.07?±?1.22 vs. 6.02?±?2.07?ng/ml, p?<?.001). Neudesin exhibited an inversely independent link with luteinizing hormone, free-androgen index, and BMI whereas it showed a positively independent link with progesterone in women with PCOS. Logistic regression analysis revealed that decreased neudesin levels were parallel with increased risk of having PCOS. Decreased neudesin levels were associated with hormonal disturbances in PCOS women, suggesting that neudesin may play a role in pathophysiology of PCOS.     

子宫内膜间质肉瘤的研究进展

子宫内膜间质肉瘤是一种来源于间叶组织的子宫肉瘤,其肿瘤细胞形似正常增殖期子宫内膜间质细胞,分为低度恶性子宫内膜间质肉瘤、高度恶性子宫内膜间质肉瘤以及子宫外内膜间质肉瘤.子宫内膜间质肉瘤早期即可能发生浸润和转移,因此早期发现、早期诊断和早期治疗对于本病具有重要的意义.但由于子宫内膜间质肉瘤组织细胞具有多分化潜能,镜下表现...     

What agent should be used to prevent recurrent preterm birth: 17-P or natural progesterone?

Preterm birth has increased over the last decade. In 2006, 12.5% of all births in the United States occurred at fewer than 37 weeks gestation. This is associated with significant health care costs as well as related neonatal morbidity and mortality. In 2003, costs related to care for infants with preterm-birth or low-birth weight exceeded 11 billion dollars. This article reviews the literature on 17 alpha-hydroxyprogesterone caproate (17-P) and natural progesterone and concludes that 17-P is indicated for prevention of preterm birth in women with a documented history of a preterm birth before 37 weeks.