Expression of KiSS-1 in rat ovary: putative local regulator of ovulation?

Kisspeptins, the products of KiSS-1 gene, and their receptor, GPR54, have recently emerged as essential gatekeepers of reproduction, mainly through regulation of GnRH secretion at the hypothalamus. However, the profound hypogonadotropism linked to GPR54 inactivation is likely to mask additional functions of this system at other levels of the gonadal axis, in which expression of KiSS-1 and GPR54 has been preliminarily reported. We describe herein the expression of KiSS-1 gene and kisspeptin immunoreactivity (IR) in rat ovary and evaluate its developmental and hormonal regulation. KiSS-1 and GPR54 mRNAs were persistently detected in adult ovary along estrous cycle. Yet, contrary to GPR54, ovarian KiSS-1 levels fluctuated in a cyclic-dependent manner, with a robust increase in the afternoon of proestrus, i.e. preceding ovulation. In addition, kisspeptin-IR was observed in rat ovary, with strong signals in theca layers of growing follicles, corpora lutea, and interstitial gland, compartments in which modest GPR54-IR was also detected. Interestingly, the rise in ovarian KiSS-1 mRNA at proestrus was prevented by blockade of preovulatory gonadotropin surge and restored by replacement with human chorionic gonadotropin as superagonist of LH. In addition, immature ovaries showed low to negligible levels of KiSS-1 mRNA, which were significantly enhanced by gonadotropin priming. In summary, we present novel evidence for the developmental and hormonally regulated expression of the KiSS-1 gene, and the presence of kisspeptin-IR, in rat ovary. The ability of the LH surge to timely induce ovarian expression of KiSS-1 at the preovulatory period strongly suggests a previously unsuspected role of locally produced kisspeptin in the control of ovulation.

Central nervous system vasculopathy in neonatal lupus erythematosus.

Central nervous system involvement in neonatal lupus erythematosus (NLE) has not been previously reported. We report four patients with NLE, all with complete congenital heart block and three with cerebral ultrasound and color Doppler flow imaging (CDFI) studies demonstrating evidence of associated vasculopathy in the gangliothalamic vasculature. CDFI confirmed blood flow through the affected vessels, indicating that blood flow was not compromised at this early stage. Short-term follow-up revealed no signs of progression of the vasculopathy, focal ischemia, gangliothalamic atrophy, or neurological impairment. Nevertheless, the implications of this finding with respect to the natural history of NLE remain to be defined, particularly in cases in which the disease develops into systemic lupus erythematosus later in life. Besides specific diagnostic studies for NLE, cerebral ultrasound, and CDFI studies are mandatory in all cases of complete congenital heart block, regardless of whether mothers are diagnosed as having connective-tissue disease or not. Neonates with signs of vasculopathy in the gangliothalamic region should be examined for NLE.

Ascorbate-supplemented media in short-term cultures of human embryos.

The present study aimed to evaluate whether ascorbate, a reactive oxygen species (ROS) scavenger, can improve fertilization and development of human embryos in vitro when added to the simple salt solution human tubal fluid (HTF) or the complex tissue culture medium Ham's F-10, which contains iron and copper in its formulation. Human oocytes, spermatozoa and embryos from 83 infertile IVF couples were randomly allocated and cultured in the presence or absence of 62.5 microM ascorbate in HTF medium (39 couples) or Ham's F-10 medium (44 couples). No significant effect of ascorbate on fertilization, number of cells and embryo grade per embryo on days 2 and 3 after insemination, or percentage of embryos showing developmental block on day 3 (those embryos that were still at the 2-cell stage) was observed when data were analysed together or divided into several groups according to the cause of infertility, quality of semen sample used for insemination and women's age in either of the two media tested. Despite these results, a positive effect of ascorbate on fertilization and embryo development in vitro cannot be totally ruled out until the effects of other, non-physiological concentrations of ascorbate and longer-term embryo cultures (to the blastocyst stage) have been tested.

New pattern of hyperechogenicity in thalamus and basal ganglia studied by color Doppler flow imaging.

Thirty-seven infants whose cerebral real-time B-mode ultrasound (CUS) documented hyperechogenic areas in the thalamus and basal ganglia (HTBG) either of linear or fine punctate pattern, were studied prospectively by color Doppler imaging (CDI). This study aimed to establish a relationship between these areas and the regional vasculature, to analyze associated disorders to establish pathogenesis, and to determine clinical significance. HTBG were diagnosed in the first 4 days of life in all but 7 infants. Different patterns of HTBG were observed: punctate in 11 infants, linear in 12, and mixed in 14. The basal ganglia were affected in all patients, 9 also had involvement of the thalamus. CDI confirmed that HTBG were allocated along the gangliothalamic vessels. Blood flow velocity waves were obtained at this level in all patients. Real-time spectral analyses were performed in 35 patients and compared with a control group of 20 healthy neonates. Differences were not significant. Computed tomography and magnetic resonance imaging failed to indicate this abnormality. Necropsy revealed basophilic deposits in the walls of involved arteries. Congenital infections manifested in 5 patients, chromosomal abnormality in 1, dysmorphic syndromes in 9 (3 unidentified), isolated congenital defects in 5, and diverse congenital disorders in 3. In the remaining 14, no congenital disorders nor infections were found. This CDI study demonstrates the vascular location of these HTBG. Supported by early CUS diagnosis, it is speculated that vascular injury in that region has a prenatal origin. This abnormality does not appear to alter regional blood flow. HTBG are associated with very heterogeneous disorders and in most patients the etiology and pathogenesis remain unclear.

Ultrasonographic findings in thalamus and basal ganglia in term asphyxiated infants.

Three severely asphyxiated term neonates demonstrated bilateral hyperechogenicity in the thalamus and basal ganglia. During evolution, areas of attenuated echogenicity appeared in these structures at the same time as periventricular cysts were evident in 2 patients with coexistent periventricular leukomalacia. All 3 patients developed ventricular dilatation; in the 2 patients with periventricular leukomalacia, the ventricular border was irregular in the outer (dorsal) margin, and interhemispheric fissures were widened as a manifestation of cerebral atrophy. Furthermore, the thalamic inner (ventral) margins of the lateral ventricles were irregular in all 3 patients. This previously unrecognized finding points to a particular form of cerebral atrophy localized in the gangliothalamic region that contributes to the development of ventriculomegaly. The reported sonographic sequence implies profound damage in the thalamus and basal ganglia in asphyxiated infants which undoubtedly has contributed to the poor outcomes of our patients.