Telomeres are shorter in placentas from pregnancies with uncontrolled diabetes.

INTRODUCTION: The intrauterine environment, including the placenta, is influenced by a variety of factors, among which is diabetes during pregnancy. These factors can affect lifetime morbidity. Senescence is a state of cellular metabolic arrest, known to be correlated with age-related diseases and is usually accompanied by short telomeres. This study evaluated telomere characteristics in placentas and in cord blood from term pregnancies complicated by uncontrolled diabetes mellitus. METHODS: Placental biopsies and cord blood were collected from 16 pregnancies with poorly controlled diabetes and from 16 healthy controls. Senescence-associated heterochromatin foci (SAHF) and senescence-associated ß-galactosidase (SAß-Gal) staining were evaluated. Apoptosis was evaluated using tunel staining. Telomere length and aggregate formation were assessed in placentas and in cord blood using Q-FISH. RESULTS: Increased SAHF (19.28% ± 7.93 vs. 7.78% ± 5.31, P < 0.001) and SAß-Gal (7.1% ± 1.32 vs. 0.8% ± 0.41, P < 0.001), but not apoptosis were present in placentas from diabetic pregnancies compared to controls. Higher percentage of trophoblasts with short telomeres (24.42% ± 12.6 vs. 4.92% ± 6.4, P = 0.013) and noticeably more aggregate formation (2.75% ± 1.14 vs. 0.62% ± 0.87, P < 0.001) were observed in diabetic placentas compared to controls. These differences were not observed in cord blood samples. DISCUSSION: Poorly controlled diabetes is related to increased senescence and shorter telomeres in placentas. Those findings may partially explain increased long-term, related morbidity.

Cycle-dependent expression of macrophage migration inhibitory factor in the human endometrium.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that was shown to promote angiogenesis and tissue remodelling. Our previous studies identified MIF as one of the principal bioactive molecules involved in endothelial cell proliferation released by ectopic endometrial cells. METHODS AND RESULTS: In the present study, we examined the expression of MIF in the human endometrium and found an interesting distribution and temporal pattern of expression throughout the menstrual cycle. Immunoreactive MIF was predominant in the glands and surface epithelium. Dual immunofluorescence analysis further identified endothelial cells, macrophages and T-lymphocytes as cells markedly expressing MIF in the stroma. Quantitative assessment of MIF protein showed a regulated cycle phase-dependent expression pattern. MIF expression increased in the late proliferative/early Secretory phase of the menstrual cycle was moderate during the receptive phase or what is commonly called the implantation window before increasing again at the end of the cycle. This pattern paralleled MIF mRNA expression determined by northern blot. CONCLUSION: The cycle phase-specific expression of MIF suggests a tight regulation and perhaps different roles for this factor in the reparative, reproductive and inflammatory-like processes that occur in human endometrium during every menstrual cycle.

Evidence for an increased release of proteolytic activity by the eutopic endometrial tissue in women with endometriosis and for involvement of matrix metalloproteinase-9.

BACKGROUND: For the implantation of endometrium in ectopic locations, remodelling of the extracellular matrix (ECM) is necessary. Many studies have shown an increased expression of various proteases in the ectopic endometrium of women with endometriosis. Few, however, have addressed possible changes in protease expression in the eutopic endometrium. METHODS AND RESULTS: Herein, we reveal an increased release of proteolytic activity by the eutopic endometrium of women with endometriosis compared with normal women (P < 0.01). Using zymography and western blotting, we identified matrix metalloproteinase (MMP)-2 and MMP-9 in the culture medium, and further found that MMP-9 secretion, as assessed by zymography and enzyme-linked immunosorbent assay (ELISA), was elevated in women with endometriosis compared with normal women (P < 0.05). No statistically significant difference in MMP-2 secretion between women with and without endometriosis was noted. However, a significant difference in the levels of the tissue inhibitor of metalloproteinases (TIMP)-1, a known MMP-9 inhibitor, was found (P < 0.05). CONCLUSION: The endometriosis-associated increase in proteolysis and imbalance between the secretion of MMP-9 and that of its natural inhibitor, TIMP-1, revealed in the culture medium of endometrial tissue may reflect in vivo the enhanced capacity of this tissue to break down the ECM in host tissues, thereby favouring its ectopic implantation and development.

Intercellular communication between Sertoli cells and Leydig cells in the absence of follicle-stimulating hormone-receptor signaling.

Effective interactions among the various compartments of the testis are necessary to sustain efficiency of the spermatogenic process. To study the intercellular communication between the Sertoli and Leydig cells in the complete absence of FSH receptor signaling, we have examined several indices of Leydig cell function in FSH receptor knockout (FORKO) mice. The serum testosterone levels were reduced in the 3- to 4-mo-old adult FORKO males compared to wild-type mice despite no significant alteration in circulating LH levels. Treatment with ovine LH resulted in a dose-dependent increase in serum testosterone levels in all three genotypes (+/+, +/-, and -/-). However, the response in FORKO males was significantly reduced. Similarly, the total intratesticular testosterone per testis was also lower, but the intratesticular testosterone per milligram of testis was significantly elevated in the FORKO males. Western blot analysis revealed an apparent higher expression of the enzyme 3beta-hydroxysteroid dehydrogenase (3beta-HSD) as well as LH-receptor density in the testis of FORKO males. Immunohistochemistry also showed an increase in the intensity of 3beta-HSD staining in the testicular sections of FORKO males. Although LH receptor binding increased per unit weight in FORKO mice, the total LH binding remained the same in all genotypes. Taken together, the results of the present study suggest that, in the absence of FSH receptor signaling, the testicular milieu is altered to affect Leydig cell response to LH such that circulating testosterone is reduced in the adult mutant. Studies are currently under way to understand the mechanisms underlying this phenomenon.

Migration and research commitments: long-term effects of national socialization.

PIP: This study examines the influence of migration on the long-term commitments by foreign trained researchers at Israel's 6 universities. Israel's scientists are trained in the US, Western Europe, and Eastern Europe, and even though these centers have different research traditions, scientific endeavor may provide a common method and outlook. The author hypothesizes relationships between different training backgrounds and long-term research commitments that influence work goals and productivity, thus affecting the operation of the local scientific community. 318 interviews held with university faculty members in the sciences during 1976-77 provide data. 40% of those surveyed are returnees from the US, 15% are US immigrants, 20% are trained in or are immigrants from Western Europe, and 10% are Eastern European immigrants. The scientists largely agree that the most imporant occupational values are to 1) select goals independently, 2) contribute to basic scientific knowledge, 3) contribute to the nation, 4) be recognized by colleagues, 5) have a secure future, 6) develop useful production processes, and 7) advance economically. Value patterns are similar among all origins, although there is some variation between Israeli returnees and those who trained in Israel. Returnees and immigrants may be dissatisfied because they are unable to fulfill expectations stemming from occupational values, and scientists who have not trained or worked outside Israel, and immigrants from Eastern Europe, feel less independent in selection of goals, and deprived in job security and economic advancement. Training in the US or Western Europe contributes to higher perceptions of success. In summary, American trained scientists are competitive and seek recognition from colleagues, Eastern European training encourages a concern with practicality and the development of more products, Western Europeans develop fewer products but product high quality publications, and Israeli trained scientists publish widely. Intermixing of Israeli trained scientists with those from the 3 centers of scientific endeavor may contribute substantially to Israel's scientific productivity.^ieng