Endometrial breakdown with sustained progesterone release involves NF-κB-mediated functional progesterone withdrawal in a mouse implant model.

Irregular uterine bleeding is a major side effect of long-acting progestogen-only contraceptives in women, and is the primary reason women discontinue their use. In this study, a mouse model of endometrial breakdown was established using a subcutaneous progesterone implant to understand how irregular bleeding begins. Although progestogens sustained decidualization, endometrial breakdown was still observed in this model. We, therefore, hypothesized that endometrial breakdown might involve functional progesterone withdrawal. Using co-immunoprecipitation assays, we observed the constitutive activation of nuclear factor kappa-b (NF-κB) p65 and its interaction with the progesterone receptor (PGR); moreover, transcriptional activity of the PGR was also repressed by NF-κB activity in primary mouse and human decidual stromal cells that mimic progesterone maintenance. Yet the ratio of PGR-B to PGR-A was not increased in the mouse model. In vivo comparison of endometrial breakdown induced by progesterone withdrawal to that seen during sustained progesterone exposure, in the presence of NF-κB inhibitors, revealed that NF-κB-mediated functional progesterone withdrawal is involved in endometrial breakdown in this implant model. These data prompt further studies to determine the homology of this functional progesterone withdrawal mechanism in human endometrium. Mol. Reprod. Dev. 83: 780-791, 2016 © 2016 Wiley Periodicals, Inc.

2-Cyano-anilinium perchlorate.

In the title compound, C(7)H(7)N(2) (+)·ClO(4) (-), the cation is almost planar (r.m.s. deviation = 0.042 Å). In the crystal structure, the cations and anions are linked into a two-dimensional network parallel to (100) by N-H⋯O hydrogen bonds.

Isonicotinonitrile-benzoic acid (1/1).

In the title 1:1 adduct, C(6)H(4)N(2)·C(7)H(6)O(2), the carboxyl group and its attached phenyl ring are essentially coplanar, being twisted from each other by a dihedral angle of only 2.05 (3)°. In the crystal, the mol-ecules are connected via O-H⋯N and C-H⋯O hydrogen bonds, building an R(2) (2)(7) ring. Mol-ecules are further linked through π-π inter-actions [centroid-centroid distance of 3.8431 (8) and 3.9094 (8) Å], leading to a one-dimensional chain parallel to the b axis.

3-(1H-Tetra-zol-5-yl)pyridinium 3-(2H-tetra-zol-5-yl)pyridinium dinitrate.

In the title compound, C(6)H(6)N(5) (+)·NO(3) (-), there are two different isomers of the cation within the asymmetric unit. The dihedral angles between the the pyridinium and tetra-zole rings are 2.54 (15) and 13.36 (18)° in the two cations. In the crystal, the packing of ions is stabilized by N-H⋯O and N-H⋯(O,O) hydrogen bonds, forming clusters composed of four ion pairs.

catena-Poly[potassium-di-µ-aqua-µ-4-(5-tetra-zolio)pyridine].

The title compound, [K(C(6)H(4)N(5))(H(2)O)(2)](n), was synthesized by hydro-thermal reaction of KOH with 4-(5-tetra-zolio)pyridine. The K atom has a distorted octa-hedral coordination environment and is coordinated by two axial N atoms from the organic ligand and by four water mol-ecules in the equatorial plane. The mol-ecules as a whole are located on crystallographic mirror planes; the K atom is also located on an inversion center. Both the water mol-ecules and the organic ligands act as bridges to link symmetrically the adjacent K atoms into polymeric chains parallel to the c axis. O-H⋯N hydrogen bonds involving the water O atoms and aromatic π-π inter-actions [centroid-centroid distance 3.80 (2) Å] between the pyridine and tetra-zole rings build up an infinite three-dimensional network.

2-(3-Pyridinio)benzimidazolium penta-chloridoanti-monate(III) monohydrate.

In the title compound, (C(12)H(11)N(3))[SbCl(5)]·H(2)O, the Sb(III) centre is surrounded by five Cl atoms and displays a distorted square-pyramidal coordination geometry. The dihedral angle formed by the plane of the imidazole ring system with the pyridine ring is 4.380 (15)°. The crystal structure is stabilized by N-H⋯Cl, O-H⋯Cl and N-H⋯O hydrogen bonds, forming a three-dimensional network.

2-(2H-Tetra-zol-5-yl)pyridinium nitrate.

In the cation of the title compound, C(6)H(6)N(5) (+)·NO(3) (-), the dihedral angle between the pyridinium and tetra-zole rings is 8.2 (2)°. The constituent ions of the compound are linked via N-H⋯O hydrogen bonds, forming helical chains running along the b axis. C-H⋯N and C-H⋯O hydrogen bonds are also observed.

1,2-Bis(1H-tetra-zol-5-yl)benzene dihydrate.

The asymmetric unit of the title compound, C(8)H(6)N(8)·2H(2)O, contains one half-mol-ecule, with the benzene ring on a centre of symmetry, and two uncoordinated water mol-ecules. The benzene ring is oriented at a dihedral angle of 34.43 (12)° with respect to the tetra-zole ring. Strong O-H⋯N hydrogen bonds link the water mol-ecules to the N atoms of the tetra-zole ring. In the crystal structure, strong inter-molecular O-H⋯O and O-H⋯N hydrogen bonds link the mol-ecules into a network. One of the water H atoms is disordered over two positions and was refined with occupancies of 0.50.

4,5-Diphenyl-2-p-tolyl-1H-imidazol-3-ium nitrate.

In the cation of the title compound, C(22)H(19)N(2) (+)·NO(3) (-), the N atom in the 3-position of the imidazole is protonated. The three pendant aromatic rings are twisted from the plane of the imadazolium ring by dihedral angles of 38.1 (1), 43.74 (9) and 20.4 (1)°. In the crystal structure, N-H⋯O and N-H⋯(O,O) hydrogen bonds link the mol-ecules to form an infinite one-dimensional chain parallel to the c axis.

2-(3-Pyridinio)benzimidazolium penta-chloridobismuthate(III) monohydrate.

In the title compound, (C(12)H(11)N(3))[BiCl(5)]·H(2)O, the Bi(III) atom is coordinated by five chloride anions in a distorted square-pyramidal geometry. The planar imidazole ring system [maximum deviation = 0.012 (3) Å] is oriented at a dihedral angle of 6.08 (5)° with respect to the protonated pyridine ring. An O-H⋯Cl inter-action links the water mol-ecule to the dianion. In the crystal structure, inter-molecular O-H⋯Cl, N-H⋯O and N-H⋯Cl inter-actions link the mol-ecules into a three-dimensional network.

3-[4-(Dimethyl-amino)benzyl-ideneamino]benzonitrile.

The mol-ecule of the title Schiff base, C(16)H(15)N(3), is non-planar and displays a trans configuration with respect to the C=N double bond. The two benzene rings make a dihedral angle of 49.24 (3)°.

2,4,6-Trimethyl-anilinium bromide.

In the title compound, C(9)H(14)N(+)·Br(-), an intra-molecular N-H⋯Br inter-action links the anion to the cation. In the crystal structure, inter-molecular N-H⋯Br inter-actions link the mol-ecules into a three-dimensional network.

4-Methyl-3-nitro-benzonitrile.

In the title compound, C(8)H(6)N(2)O(2), the nitro group is rotated by 23.2 (3)° out of the plane of the benzene ring. The crystal structure is stabilized by van der Waals inter-actions.

2-(3-Nitro-phen-yl)-4,5-diphenyl-1H-imidazol-3-ium chloride.

The title compound, C(21)H(16)N(3)O(2) (+)·Cl(-), contains two organic cations with similar conformation and two chloride ions in the asymmetric unit. The imidazole and benzene rings are twisted with respect to each other [dihedral angles of 24.05 (16), 24.31 (16) and 50.38 (13) in one cation and 27.70 (15), 25.07 (16) and 45.86 (14)° in the other]. The crystal packing is stabilized by N-H⋯Cl hydrogen bonds, forming an infinite one-dimensional chain parallel to the c axis.

2-Cyano-anilinium nitrate.

In the title compound, C(7)H(7)N(2) (+)·NO(3) (-), all atoms of the cation, with the exception of two H atoms of the NH(3) group, lie on a mirror plane, while the anion lies across this plane with the N and one O atom on the mirror plane. In the crystal structure, the organic cations and NO(3) (-) anions are linked by N-H⋯N and N-H⋯O hydrogen bonds, forming a two-dimensional network parallel to (100).

Synthesis and anticonvulsant activity of 1-substituted-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline.

Starting from 6-hydroxy-3,4-dihydro-1H-quinoline-2-one, a series of 1-substituted-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines was synthesized and their structures were characterized using IR, 1H-NMR, MS, and elemental analysis techniques. Anticonvulsant activity was evaluated in the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scMet) test, and rotarod neurotoxicity test. The most active compound was 7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline 4a. Its ED50 in the MES and scMet tests was 17.3 and 24 mg.kg-1, respectively. The safest compound was 4 g, 1-phenyl-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline, with TD50 and protective index (PI) (PI=TD50/ED50) values of greater than 300 mg.kg-1 and 13, respectively. The PI value of compound 4 g was better than that of most marketed drugs. Structure-activity relationships are also described in this paper.

[Detection of cell-free fetal DNA in the urine of pregnant women by nested polymerase chain reaction].

OBJECTIVE: To investigate the clinical feasibility of fetal sex determination by using nested polymerase chain reaction (PCR) to detect cell-free fetal DNA in the urine of pregnant women. METHODS: The urine specimens of 40 healthy predelivery women were centrifuged. The DNA in the specimens of supernatant was extracted by using of QIAamp Viral RNA Mini Kits. Nested PCR was used to specifically amplify the SRY gene, 300 bp in length, on Y chromosome in order to detect the fetal DNA from the women bearing male fetuses. One specimen of normal man's urine and one specimen of non-pregnant woman's urine were used as controls for each specimen from pregnant women. The results were confirmed by the sexes of neonates examined after birth. RESULTS: Amplified band of SRY was found in 6 specimens. Sex examination after delivery showed 21 male neonates and 19 female neonates. The positive rate of detection of SRY gene was 28.6% (6/21) and the false negative rate was 71.4%, and false positive rate was 0. Five out of the 6 cases with positive results showed positive 2 times and one out of the 6 cases only showed positive at the second time. CONCLUSION: There is cell-free fetal DNA in the urine of pregnant women. Nested PCR is useful in detection of fetal sex, however, still with a rather low positive rate.