Faulty spindle checkpoint and cohesion protein activities predispose oocytes to premature chromosome separation and aneuploidy.

Aneuploidy accounts for a major proportion of human reproductive failures, mental and physical anomalies, and neoplasms. To heighten our understanding of normal and abnormal chromosome segregation, additional information is needed about the underlying molecular mechanisms of chromosome segregation. Although many hypotheses have been proposed for the etiology of human aneuploidy, there has not been general acceptance of any specific hypothesis.

Urolithiasis in pregnancy: Current diagnosis, treatment, and pregnancy complications.

Unlabelled: Urolithiasis complicates up to one in every 200 pregnancies; consequently, the practicing obstetrician should be aware of the symptoms of urolithiasis, the diagnostic procedures available for its diagnosis, and their associated risks. These include ultrasound, urography, and magnetic resonance imaging. Diagnosis of urolithiasis during pregnancy can be a challenge as a result of the normal physiological changes of pregnancy.

Post-ovulatory aging of mouse oocytes leads to decreased MAD2 transcripts and increased frequencies of premature centromere separation and anaphase.

Numerous cytological and biochemical alterations occur as mammalian oocytes age post-ovulation. Some of these changes can predispose cells to aneuploidy. The objective of this study was to test the hypothesis that the level of MAD2 spindle assembly checkpoint (SAC) transcripts decrease as mouse oocytes age post-ovulation and that this decrease was associated with chromosome missegregation.

Loss of heterozygosity occurs via mitotic recombination in Trp53+/- mice and associates with mammary tumor susceptibility of the BALB/c strain.

Loss of heterozygosity (LOH) occurs commonly in cancers causing disruption of tumor suppressor genes and promoting tumor progression. BALB/c-Trp53(+/-) mice are a model of Li-Fraumeni syndrome, exhibiting a high frequency of mammary tumors and other tumor types seen in patients. However, the frequency of mammary tumors and LOH differs among strains of Trp53(+/-) mice, with mammary tumors occurring only on a BALB/c genetic background and showing a high frequency of LOH, whereas Trp53(+/-) mice on a 129/Sv or (C57BL/6 x 129/Sv) mixed background have a very low frequency of mammary tumors and show LOH for Trp53 in only approximately 50% of tumors.

Transient exposure to the Eg5 kinesin inhibitor monastrol leads to syntelic orientation of chromosomes and aneuploidy in mouse oocytes.

Aneuploidy may result from abnormalities in the biochemical pathways and cellular organelles associated with chromosome segregation. Monastrol is a reversible, cell-permeable, non-tubulin interacting inhibitor of the mitotic kinesin Eg5 motor protein which is required for assembling and maintaining the mitotic spindle. Monastrol can also impair centrosome separation and induce monoastral spindles in mammalian somatic cells.

Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, induces premature separation of sister chromatids during meiosis I and aneuploidy in mouse oocytes in vitro.

Recent advances in understanding some of the molecular aspects of chromosome segregation during mitosis and meiosis provide a background for investigating potential mechanisms of aneuploidy in mammalian germ cells. Numerous protein kinases and phosphatases have important functions during mitosis and meiosis. Alterations in these enzyme activities may upset the normal temporal sequence of biochemical reactions and cellular organelle modifications required for orderly chromosome segregation.

Vanadate, an inhibitor of tyrosine phosphatases, induced premature anaphase in oocytes and aneuploidy and polyploidy in mouse bone marrow cells.

Protein tyrosine phosphatases are needed for activating maturation promoting factor, meiotic spindle assembly and spindle checkpoint inactivation. The protein phosphatase inhibitor vanadate was used to upset the kinase-phosphatase equilibrium during oocyte maturation (OM) and the metaphase anaphase transition (MAT) prior to cytogenetic analyses of mouse oocytes and bone marrow cells. ICR females received pregnant mare serum gonadotrophin (PMSG) and 48h later received human chorionic gonadotrophin (hCG).

MG-132, an inhibitor of proteasomes and calpains, induced inhibition of oocyte maturation and aneuploidy in mouse oocytes.

BACKGROUND: Although chromosome missegregation during oocyte maturation (OM) is a significant contributor to human morbidity and mortality, very little is known about the causes and mechanisms of aneuploidy. Several investigators have proposed that temporal perturbations during OM predispose oocytes to aberrant chromosome segregation. One approach for testing this proposal is to temporarily inhibit the activity of protein proteolysis during OM.

Oral misoprostol before office endometrial biopsy.

Objective: To evaluate oral misoprostol use before office endometrial biopsy.

Methods: Forty-two nonpregnant women aged 35-77 years were randomized to a prospective, double-blind study to receive either 400 microg oral misoprostol or placebo 3 hours before office endometrial biopsy. Misoprostol effects were assessed by 1) cervical resistance, 2) ease of performing the endometrial biopsy, 3) success rate of obtaining an endometrial biopsy, 4) pain intensity associated with the endometrial biopsy, and 5) adverse clinical side effects.