Invited commentary: a single nucleotide polymorphism in BMP15 is associated with high response to controlled ovarian hyperstimulation

A report has been published which shows a connection between single nucleotide polymorphisms (SNP) in the bone morphogenetic protein 15 (BMP15) gene and ovarian hyperstimulation syndrome (OHSS) in women, similar to reported effects of heterozygous BMP15 point mutations in sheep. The report also describes the near-significant presence of another BMP15 gene SNP correlated with a low response to ovarian stimulation. Previous studies associated two SNP with anovulation or infertility in women with polycystic ovary syndrome, and heterozygosity for another BMP15 SNP resulted in ovarian dysgenesis and hypergonadotrophic failure. In sheep, homozygous point mutations or immunization against BMP15 led to follicular developmental arrest, ovarian dysgenesis and streak ovaries. In mammalian (including human) ovaries BMP15 and its three receptors were shown to be expressed from primary or primordial follicular stages, suggesting that BMP15 might also be involved in activating primordial follicles, and could possibly serve as a marker of follicular reserve. BMP15 also inhibited follicle stimulating hormone receptor expression, was associated with cumulus expansion and its high follicular-fluid concentration was correlated with improved oocyte and embryo quality. Thus, BMP15 seems to be an important regulator of ovarian function. Further studies are needed to clarify its roles in human female fertility.     

Applicability of Willems method for dental age estimations in Tunisian children

Aim

This study aims to evaluate the applicability of Willems method in a sample of Tunisian children. Panoramic x-ray photographs of 500 children (241 females, 259 males) aged between 5 and 15 years were examined. The mean absolute error (MAE) was performed to assess the accuracy of age estimation. The chronological age minus dental age (CA-DA) was determined for each age group and for each gender. Independent samples t-test was employed to compare the differences between genders.

Localization and action of Dragon (repulsive guidance molecule b), a novel bone morphogenetic protein coreceptor, throughout the reproductive axis

Bone morphogenetic proteins (BMPs) play important roles in reproduction including primordial germ cell formation, follicular development, spermatogenesis, and FSH secretion. Dragon, a recently identified glycosylphosphatidylinositol-anchored member of the repulsive guidance molecule family, is also a BMP coreceptor. In the present study, we determined the tissue and cellular localization of Dragon in reproductive organs using immunohistochemistry and in situ hybridization. Among reproductive organs, Dragon was expressed in testis, epididymis, ovary, uterus, and pituitary. In the testis of early postnatal mice, Dragon was found in gonocytes and spermatogonia, whereas in immature testes, Dragon was only weakly expressed in spermatogonia. Interestingly, pregnant mare serum gonadotropin treatment of immature mice robustly induced Dragon production in spermatocytes. In adult testis, Dragon was found in spermatocytes and round spermatids. In the ovary, Dragon was detected exclusively within oocytes and primarily those within secondary follicles. In the pituitary, Dragon-expressing cells overlapped FSH-expressing cells. Dragon was also expressed in a number of cell lines originating from reproductive tissues including Ishikawa, Hela, LbetaT2, MCF-7, and JEG3 cells. Immunocytochemistry and gradient sucrose ultracentrifugation studies showed Dragon was localized in lipid rafts within the plasma membrane. In reproductive cell lines, Dragon expression enhanced signaling of exogenous BMP2 or BMP4. The present studies demonstrate that Dragon expression is dynamically regulated throughout the reproductive tract and that Dragon protein modulates BMP signaling in cells from reproductive tissues. The overlap between Dragon expression and the functional BMP signaling system suggests that Dragon may play a role in mammalian reproduction.     

Takayasu's arteritis revealed by aortic regurgitation with ascending aortic aneurysm (About 2 cases)

Aortic regurgitation caused by non-specific aortitis is relatively rare, and is now considered as an important risk factor related to mortality. Aortic valve replacement surgery is the only curative treatment. Aneurismal dilatation of the ascending thoracic aorta associated with aortic regurgitation is a rare involvement in Takayasu, there are many difficult problems in surgical treatment of this lesion, because of its inflammatory nature, so steroid therapy before and after surgery is therefore vital. We report the cases of tow young Moroccans women (32-35 years-old) with an ascending aortic aneurism associated to aortic insufficiency. The subsequent evaluation of the entire aorta, demonstrated the presence of multiple steno-occlusive lesions. Aortic valve replacement was performed associated with graft replacement of the ascending aorta without coronary artery reimplantation. Histopathological examination of the ascending aorta and aortic valve, showed findings in favour Takayasu's arteritis.     

Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators

Pentahydroxyflavone dihydrate, quercetin (QU) is one of common flavonols biosynthesized by plants and has been suggested to modulate inflammatory responses in various models. In the present study, we investigated in vivo effects of oral or intra-cutaneous QU in chronic rat adjuvant-induced arthritis (AA). Growth delay and arthritic scores were evaluated daily after AA induction in Lewis rats. Oral administration of QU (5 x 160 mg/kg) to arthritic rats resulted in a clear decrease of clinical signs compared to untreated controls. Intra-cutaneous injections of lower doses (5 x 60 mg/kg) of QU gave similar anti-arthritic effects, while 5 x 30 mg/kg concentrations were inefficient in this respect. Finally, injection of relatively low QU doses (5 x 30 mg/kg) prior to AA induction significantly reduced arthritis signs. As QU was suggested to inhibit macrophage-derived cytokines and nitric oxide (NO), we then analyzed macrophage response ex vivo. Anti-arthritic effects of QU correlated with significant decrease of inflammatory mediators produced by peritoneal macrophages, ex vivo and in vitro. These data indicate that QU is a potential anti-inflammatory therapeutic and preventive agent targeting the inflammatory response of macrophages.     

IgG exchange as a means of partial correction of anomalies in rat embryos in vitro, induced by sera from women with recurrent abortion

Many recurrent abortions have an unknown aetiology. A significant proportion of sera from women with spontaneous abortions induced 50% or more anomalies (‘high risk’ sera) in cultures of 10.5-day-old rat embryos. Because it is assumed that the teratogenic factor(s) in recurrent abortion is often an immunoglobulin G (IgG) antibody, it was attempted to reduce the rate of anomalies induced by high risk sera by removing the IgG fractions and adding IgG fractions from control sera (sera from women in a normal second trimester of pregnancy and after delivery). Concomitantly, an attempt was made to induce anomalies in embryos cultured in control sera by adding IgG fractions from high risk sera. It was found that among the high risk sera there were three groups, according to the response to the IgG exchange: (1) a group in which IgG exchange ‘corrected’ the anomalies in high risk sera, whereas it induced anomalies in control sera; (2) a group in which anomalies were found both in embryos cultured in high risk sera and those cultured in control sera; (3) a group in which the IgG exchange did not affect the results in the ‘experimental’ or ‘control’ embryos. Examination by transmission electron microscopy, of yolk sacs cultured in sera with IgG from women belonging to the third group did not reveal ultrastructural changes. In conclusion, in some high risk sera the teratogenic factor appears to be an IgG only; in others, teratogenicity is brought about not only by an IgG, but also by additional teratogenic factor(s); in the last group, the teratogenic factor(s) does not appear to be an IgG at all.     

Primary intracranial sarcomatoid carcinoma arising from a recurrent/residual epidermoid cyst of the cerebellopontine angle: a case report

Primary intracranial squamous cell carcinomas (SCCs) are rare and mostly associated with an intracranial epidermoid or dermoid cyst. Sarcomatoid carcinoma is a rare biphasic tumor composed of both carcinomatous and sarcomatous components and has not previously been reported as a primary intracranial tumor. Here, we present a case of a 60-year-old man with a primary intracranial sarcomatoid carcinoma, arising from the remnants of the previously resected epidermoid cyst in the cerebellopontine angle. The resected material had portions of an epidermoid cyst lined by normal and dysplastic squamous epithelia and invasive keratinizing SCC. This area was in continuity with areas of highly pleomorphic, anaplastic sarcomatoid cells. Brisk mitotic activity and extensive areas of necrosis were found. On immunohistochemical staining, the cells of the conventional SCC were positive for cytokeratin 5/6, pancytokeratin, epithelial membrane antigen, p63, and p53. The sarcomatoid cells were diffusely and strongly positive for vimentin, p53, smooth muscle actin, and, focally, muscle-specific actin. Occasional sarcomatoid cells coexpressed cytokeratin 5/6, pancytokeratin, p63, and S100 protein. The patient subsequently developed leptomeningeal spread and died 4 months after the second surgery. This rare entity expands the morphologic spectrum encountered in primary intracranial carcinoma.