Submicroscopic unbalanced translocation resulting in del10p/dup13q detected by subtelomere FISH.

Chromosomal rearrangements involving the (sub)telomeres are an important cause of human genetic diseases: with the development of advanced molecular cytogenetic methods they have been identified as a major cause of mental retardation and/or congenital malformation syndromes. We identified a cryptic unbalanced de novo translocation 10p/13q by subtelomere FISH in a boy with mental and growth retardation (karyotype: 46,XY,der(10)t(10;13)(p15.1;q34)(D10S2488-,D13S296+)). Craniofacial dysmorphisms included frontal bossing, epicanthal folds, long philtrum, thin upper lip, short nose, mild retrognathy and a flat midface. In addition the patient had ASDII, a pyloric stenosis, bilateral inguinal hernias and cryptorchidism. His psychomotor development was significantly delayed. Microsatellite typing revealed the paternal origin of the two chromosomes involved in the rearrangement. By comparing our case with previously published patients with similar aberrations we conclude that the congenital malformations in our case are associated with the partial 10p deletion. The craniofacial features might be attributed to the 13q duplication. The identification of a 10p/13q translocation in our case highlights the importance of searching for cryptic subtelomeric imbalances in mentally retarded patients and helps to further delineate genotype-phenotype correlations in rare chromosomal disturbances.

Further arguments for non-fortuitous association of Potter sequence with XYY males.

Although large studies on sex chromosome abnormalities have not detected a higher incidence of malformations in 47,XYY males, several case reports suggest that there is an association between renal agenesis or cystic dysplasia of the kidney and XYY status. The authors report 3 further infants with XYY karyotype who had urogenital malformations leading to Potter sequence. On the basis of our observations and review of the literature, we suggest that the XYY syndrome and Potter sequence are more significantly associated than expected by pure coincidence.

Passive immunization with anti-oestradiol antibodies during the luteal phase of the menstrual cycle potentiates the perimenstrual rise in serum gonadotrophin concentrations and stimulates follicular growth in the cynomolgus monkey (Macaca fascicularis).

Three unilaterally ovariectomized cynomolgus monkeys, in which menstrual cycles were driven by pulsatile infusion of synthetic GnRH at a fixed frequency of 1 pulse/h, were provided with a continuous infusion of ovine anti-oestradiol gamma-globulin beginning 13 days after ovulation and continuing for 7 days thereafter. Plasma concentrations of both FSH and LH rose at the start of the antibody infusion and remained elevated throughout the 7-day treatment regimen when compared with control (non-immune gamma-globulin-treated or untreated) animals. Morphometric examination of ovaries at the end of the experimental and control infusions revealed a significant difference (P less than 0.05) in the average size of the largest non-atretic antral follicle in each of the experimental animals when compared with that of the control animals (2.45 +/- 0.23 vs 1.30 +/- 0.53 mm). Collectively, the 3 control animals possessed 9 non-atretic antral follicles greater than 1.0 mm diameter, none of which exceeded a diameter of 2.0 mm. In contrast, the experimental animals had 28 non-atretic follicles of greater than 1.0 mm diameter, 8 of which exceeded 2.0 mm. These observations are consistent with the hypothesis that oestrogen and progesterone are the primary agents responsible for the restraint of gonadotrophin secretion and preovulatory follicular growth during the luteal phase of the primate menstrual cycle.

Interference with the gonadotropin-suppressing actions of estradiol in macaques overrides the selection of a single preovulatory follicle.

We examined the role of the gonadotropin-suppressing effects of estradiol on the maturation of a single ovulatory follicle in cynomolgus monkeys (Macaca fascicularis) by administering ovine antiestradiol antibodies during the mid through late follicular phase of the menstrual cycle. In each of three control animals, when the ovary containing the maturing follicle was removed during the late follicular phase, histological examination of the remaining ovary 10 days later revealed the presence of a single large maturing follicle. In contrast, in three experimental animals, when estradiol antibodies were infused from days 5 through 10 after unilateral ovariectomy, serum FSH and LH concentrations were elevated above those of control animals, and histological examination of ovaries 10 days after unilateral ovariectomy revealed the presence of two large maturing follicles in the remaining ovary of two animals and four large maturing follicles in the remaining ovary of the third animal. The ability of follicles recruited during passive immunization with estradiol antibodies to respond to exogenous gonadotropin was studied. In three control animals, the maturing follicle was destroyed on day 10 of the follicular phase, and 3 days later, each animal received an ovulatory dose of human CG. None of these control animals produced progesterone. In three experimental animals a continuous infusion of estradiol antibodies was initiated on day 5 of the follicular phase, and the largest antral follicle was destroyed on day 10. Three days thereafter the antibody infusions were terminated and each animal received an ovulatory dose of human CG. Each of these animals produced progesterone despite the destruction of the largest follicle 3 days earlier. These observations demonstrate that estradiol is the principal ovarian modulator of gonadotropin secretion during the follicular phase of the cycle and that interference with the gonadotropin-suppressing actions of estradiol results in continued recruitment and maturation of secondary follicles in the presence of a dominant follicle.

Gonadotropin-binding sites in the rhesus monkey ovary: role of the vasculature in the selective distribution of human chorionic gonadotropin to the preovulatory follicle.

These experiments were initiated to determine if differences exist in the vasculature of individual follicles in the rhesus monkey ovary during the late follicular phase of the menstrual cycle and to determine whether differences in vascularity result in differential exposure of certain follicles to gonadotropic hormones. The density of blood vessels within the thecal layer of the dominant follicle and other antral follicles was determined in ovaries from four animals removed on day 9 or 10 of the menstrual cycle. Blood vessels were identified using a histochemical stain for hemoglobin. Morphometric analysis indicated that the percentage of the thecal layer occupied by blood vessels in the dominant follicles (48%) was significantly greater (P less than 0.005) than that of other smaller antral follicles either within the same ovary as the dominant follicle (24%) or in the contralateral ovary (26%). To determine if differences in vascularity result in a differential supply of gonadotropins to the dominant follicle, we studied, by autoradiography, the in vivo and in vitro binding of [125I]hCG in four rhesus monkeys on day 9 of the menstrual cycle. Results of in vitro binding studies indicated that the thecal layer of virtually every antral follicle possessed hCG-binding sites. However, when [125I]hcg was injected iv into animals and allowed to distribute via the vasculature, the dominant follicle was heavily labeled while other smaller antral follicles accumulated little, if any, radioiodinated hCG. These observations indicate that increased vascularization of individual follicles results in preferential delivery of gonadotropins, and suggest that blood flow to individual follicles may play an instrumental role in the selective maturation of the preovulatory follicle in the rhesus monkey.

Characterization of ovarian folliculogenesis during the luteal phase of the menstrual cycle in rhesus monkeys using [3H]thymidine autoradiography.

The characteristics of the early stages of ovarian follicular maturation were investigated in rhesus monkeys during the luteal phase of the menstrual cycle using a novel procedure to supply low levels (10 microCi) of [3H]thymidine directly to ovaries in vivo. With this labeling procedure, plasma levels of [3H]thymidine did not exceed 8 cpm/microliters and labeled ovarian cells were readily identifiable by autoradiography. Results from four animals studied during the luteal phase of the cycle indicated that all sizes of preantral follicles contained granulosa cells that incorporated [3H]thymidine. There was a progressive increase in the percentage of labeled follicles in direct relationship to follicular size; 10% of the single granulosa cell layer follicles were labeled and the labeling frequency increased to greater than 60% in the large (> 6 granulosa cell layer) preantral follicles. The labeling frequency of all size classifications of preantral follicles during the luteal phase of the menstrual cycle was similar to that of an animal which was studied during the follicular phase of the menstrual cycle. The results suggest that growth of ovarian follicles to the preantral stage occurs during the luteal phase of the menstrual cycle in rhesus monkeys, and thus the cessation of preovulatory folliculogenesis during the luteal phase of the cycle is not due to a defect of growing preantral follicles.

Duration of the cycle of the seminiferous epithelium in the prairie vole (Microtus ochrogaster ochrogaster).

The cycle of the seminiferous epithelium in M. o. ochrogaster was divided into eight readily recognizable stages based on the morphology of the developing spermatid. The mean relative frequencies of Stages I through VIII were 11.6, 19.25, 20.00, 19.00, 8.42, 6.17, 9.25 and 6.58%, respectively. The duration of one cycle of the seminiferous epithelium in this species, as determined from autoradiographs of thymidine-H3 injected testes was 7.17 days (S.E. +/- 0.03). This is the shortest spermatogenic cycle reported for any mammal to date. The approximate durations of the meiotic prophase, meiotic divisions, and spermiogenesis were 8.8, 0.4 and 12.2 days, respectively. The entire process of spermatogenesis was estimated to span approximately 28.68 days. The number of cycles that spermiogenesis spanned in this species was compared to values calculated for other species. Values within groups of related species appear relatively constant, but between groups the values are variable.