Streptonigrin: effect on the first meiotic metaphase of the mouse egg.

Streptonigrin, an antibiotic and antitumor agent, alters the chromosomes of the mouse ovum during meiosis. Agglutination of bivalents or achromatic gaps and breaks occurred in the larger pairs both in vitro and in vivo. This newly detected cytogenetic effect suggests that such agents can gain access to developing mammalian ova and destroy the normal progress of meiosis.

The pachytene chromomere map of the oocyte of the Turkish hamster (Mesocricetus brandti).

A study of the chromomere maps of the sex and twenty autosomal bivalents of Turkish hamster pachytene oocytes was carried out. The average total number of chromomeres in early/mid pachytene autosomes was 280 with 91 on the p (short arm) and 189 on the q (long arm). The submetacentric X1 chromosome had 20 chromomeres and the metacentric X2 had 27. Comparisons of the number and location of oocyte chromomeres are made with the pachytene spermatocyte chromomere maps of this species.

Alterations of mammalian oocyte meiosis I with divalent cations and calmodulin.

Experiments using a Ca2+/Mg2+, serum free media were carried out aimed at clarifying proposed effects of these divalent cations on in vitro meiotic maturation of mouse and cow oocytes. Agents known to perturb intracellular Ca2+ or calmodulin were also studied. Total absence of both cations restricts both oocyte species from completing meiosis I. Media containing Mg2+ and no Ca2+ permitted some maturation in both species. Absence or small amounts of Mg2+ in the media containing control amounts of Ca2+ was much more inhibitory for the cow than the mouse oocyte. Studies of mouse oocyte maturation with Verapamil, Epinephrine and A23187 demonstrated an inhibition of maturation perhaps by the intracellular Ca2+ changes these agents are alleged to induce. A dependency of mouse oocyte maturation on active Ca-Calmodulin complexes was suggested by the calmodulin inhibitor studies.

Aging and X chromosome loss in the human ovary.

A study of the incidence of X chromosome loss from the mitotic complement of human ovary has demonstrated a small loss beginning between ages 36 and 45 years and increasing additively to age 75. This was earlier and less than has been shown for blood. In ovarian tissue, autosomal chromosomal loss declined with age while X loss increased. Though no correlation of X loss could be demonstrated with the clinical state of the menstrual cycle, there was a greater loss of all chromosomes in normally cycling subjects than in perimenopausal and postmenopausal subjects. The possibility that the menopause is initiated in the ovary is raised by findings of these correlates of aging.

Chromosome 21 behavior during fetal oogenesis in Down's syndrome.

Oogenesis of four cases of 47,XX,+21 at gestational ages of 19 and 20 weeks was studied using pachytene cytogenetic methods. We found a variable pattern of pairing behavior of the 21 chromosomes among the cases, which included partially synapsed trivalents, a bivalent plus a univalent, and three univalents. The bivalent/univalent conformation of 21 chromosomes predominated. Pachytene chromomere maps were normal for all autosomal bivalents in 84 oocytes analyzed, except for minor variations in some 21 chromosomes. This complex system of pairing behavior of the 21 chromosomes theoretically affects subsequent disjunctional behavior and therefore may account for the observations of normal and trisomic progeny observed for Down's syndrome mothers. Further study of meiotic behavior during all stages of oogenesis in such patients would provide essential data for predicting chromosomal outcome of pregnancy in this population.

Some characteristics of oogenesis in the female Turkish hamster subjected to modified environments.

The hibernating female Turkish hamster (Mesocricetus brandti) was utilized for a study of possible in vivo effects of cold on oocyte maturation. Such a physiologic model offered an opportunity to analyze the ability of oocytes exposed to prolonged periods of reduced core temperature and/or light to subsequently mature to Metaphase II. Detailed observations of core temperatures, torpor/arousal, serum estradiol, and ovarian histology were made. An average incidence of 37.7% binuclearity was found in the germinal vesicle, metaphase I and II occytes of this species. Maturation to Metaphase II of total chromosome complements did not vary significantly in the experimental groups compared with the control, but aneuploidy was detected in the oocytes of animals exposed to reduced temperature or light. An effect of in vivo reduced core temperatures on oocyte chromosome complements validates many of the published in vitro studies with temperature reduction. The model presents an excellent physiologic system for perturbing and analyzing many aspects of mammalian oocyte development.

Further studies of inhibitors of in vitro mammalian oocyte maturation.

Studies of luteinizing hormone (LH)-mediated serum inhibition and of follicular fluid and granulosa cell inhibition of in vitro porcine, ewe, and cow oocyte meiotic maturation have been carried out. A porcine serum inhibitor or inhibitors with a molecular weight above 15,000, similar to the ewe and cow serum inhibitor(s), have been demonstrated. An LH-inactivated inhibitor or inhibitors in fluid from medium-sized ewe and cow follicles have been shown and a minimally effective porcine follicular fluid inhibitor has been confirmed. The estimated molecular weight of these inhibitors is below 1,000. Granulosa cells from the three species were not found to be dramatically inhibitory. It is postulated that the follicular fluid inhibitor(s) may be derived from the larger serum molecule(s) by an action of LH within an intermediate cell type.

PIP: The inhibitory effects of luteinizing hormone (LH)-mediated serum and of follicular fluid and granulosa cells on the in vitro oocyte meiotic maturation of sows, ewes, and cows were investigated. Oocyte meiotic maturation was delayed by a porcine serum inhibitor(s) was evident in fluid from medium-size ewe and cow follicles. A minimally effective follicular fluid inhibitor was demonstrated in sows. The molecular weights of these inhibitors was estimated to be less than 1000. Granulosa cells did not have a marked inhibitory effect in any of the 3 species. It is suggested that follicular fluid inhibitor(s) may be derived from larger serum follicles by some activity of LH within an intermediate cell type.

A quantitative analysis of mitochondria during fetal mouse oogenesis.

A quantitative analysis of mitochondrial populations during the meiotic prophase of mouse oogenesis was carried out. The mean absolute area occupied by mitochondria and the mean number of mitochondria per cell increases in a linear fashion from pachytene through dictyate. The mean area occupied by mitochondria increases at pachytene and thereafter. Both small and large aggregations of mitochondria are seen, particularly during the later stages of prophase. Vacuolated mitochondria are present from preleptotene through pachytene. Mitochondria show major dynamic changes throughout fetal mouse oogenesis, which may suggest significant functional activities yet to be elucidated.

Preliminary pharmacokinetic studies of Ukrain in rats.

Ukrain (thiophosphoric acid derivative of Chelidonium majus L. alkaloids) was administered to rats i.p. at a dose of 28 mg/kg (equivalent to 0.1 LD50). A high performance liquid chromatography (HPLC) method for rapid determination of Ukrain in plasma has been described. It was found that Ukrain rapidly penetrated into the plasma of the rats and the elimination of the drug from the plasma was slower. The results obtained were as follows: absorption rate constant ka = 0.0432 [min-1]; elimination rate constant K = 0.0113 [min-1]; drug half-life t1/2 = 61.32 min; actual concentration of Ukrain in the plasma C = 33 e-0.0113t - 39 e-0.0432t [microgram/ml]; and delay in drug absorption T0 = 5.23 min.

Unilateral fixation of the ossicular chain associated with G-group chromosome deletion.

Unilateral fixation of the middle ear ossicles and possible delayed pubescence were associated with a short-arm deletion of one of the G-group chromosomes in a 15-year-old Negro girl. A similar chromosomal abnormality was found in the mother and three of six siblings without any clinical evidence of middle ear disease. The association of G-group deletions with other hereditary disease of bone suggests, however, that a pathogenic relationship may exist between them.