Sequential aspects of spontaneous abortion: maternal age, parity, and pregnancy compensation artifact

At least 3 hypotheses predict that spontaneous abortion risk differs during reporductive history: genuine maternal age effects change individual risks; genuine birth order effects change individual risks; and variant individual risks, which are really independent of both age and parity, produce an artifactual association of risk with age in populations of women. The availability of large numbers of reproductive histories recorded on magnetic tape by the Collaborative Study on Cerebral Palsy provides an opportunity to weigh these hypotheses. Information was gathered between mid-1959 and mid-1966 by 13 hospitals, mostly east of the Mississippi. Random samples of essentially all women registering in the obstetric clinics of the collaborating institutions entered the study. Generally, these women came from poorer urban areas. Data are taken from the interviews at 1st registrations only. At this time, women had prior reproductive histories of varying lengths. The data are analyzed to yield broad comparative evaluations of the maternal age, parity, and artifact hypotheses. When the logit transforms of abortion risks were regressed on maternal age, the linear component was positive and significant at the 1% level in every ethnic group. In all categories except blacks, the fit to such a simple model was quite adequate. Fit in the case of the blacks was disturbed by the high rate among 13-year olds and the low rate among 37-year olds. The 37-year old black sample was the only one to depart markedly from the trend of increased risk at high age. Primary analysis of birth order defects used Slater's (1962) rank order statistic on a group of histories. In every ethnic category the observed mean value of Slater's statistic exceeds its expected value of 0.5; every standardized deviation has a negligibly small probability when tested against the normal distribution. The conclusin is that spontaneous abortions tend to come late in a reproductive history. The white data showed a definite trend contrary to expectation under the pregnancy compensation hypothesis. Although not significant in the "o" (liveborn) versus "x" (abortion) contrast, the lowering trent in maternal age with prior abortion experience was signifixant for the longer histories. Equally surprising was the apparent positive finding in the black data. In sum, the data clearly showed that among women with histories mixing spontaneous abortions and live births, risk of abortion was greater at higher parity. Although the women sampled tended to be young, and increase of risk with age was demonstrated in the white sample. These effects were not because of sample biases. Black age effects were possibly confounded with pregnancy compensation artifact which can mimic aging influence in unselected samples.     

Independent effects of maternal age and birth order on the incidence of selected congenital malformations

Incidence rates, specific for maternal age and birth order, were calculated for 16 categories of congenital malformations reported on birth certificates from a population of more than 8 million registered, white, single livebirths. With maternal age held constant, none of the malformations showed increasing incidence as birth order increased. Hypospadias, esophageal defects, omphalocele, and Down syndrome showed evidence of decreasing incidence as birth order increased. Some of the other malformation categories showed an excess of 1st births in most age groups, while no relation to birth order was observed in the incidence of other malformations. By contrast, most of the malformations analyzed exhibited increasing incidence as maternal age increased. Especially high rates of several malformations were observed among 1st births to women over age 40.     

Influence of maternal age, parity and social class on perinatal mortality in Scotland: 1960-82

This study examines secular changes in the influence of maternal age, parity and social class on perinatal mortality in Scotland. Using cross-sectional national data on all Scottish legitimate births the effects of these factors are estimated on the risk of stillbirths, neonatal and perinatal deaths, and the extent to which the current pattern of relative risks in the early 1980s has changed over the past 2 decades is investigated. Social class is used as a crude measure of relative as opposed to absolute differences in socioeconomic conditions which may influence reproductive outcomes. The effects of age, parity and social class are estimated using logistic models. The most parsimonious model adequately describing the data is provided by a main effects model without interactions. Despite changes in reproductive behavior, improved access to maternity services and more effective perinatal care, the influence of maternal age and social class on perinatal mortality remained unchanged between 1960 and 1982. Although the absolute risks of stillbirths and neonatal deaths declined in all maternal age groups, this improvement was not accompained by a significant change in the relative risks traditionally associated with age. Despite no significant changes in the traditional J-shaped association between parity and stillbirths, cross-sectional analysis shows that in the early 1980s the risk of both neonatal and perinatal deaths decreased as parity increased. This finding is consistent with the pattern of risks observed in longitudinal studies and retrospective surveys of reproductive histories. In view of the stability of age, parity and social class effects on the risk of perinatal mortality, little if any of the overall decrease in Scottish stillbirth and neonatal death rates can be attributed to a significant narrowing of relative risks. The results suggest that the attributable risk of high maternal age or low social class on perinatal mortality is negligible. Future improvements in perinatal mortality are thus likely to result from a continuation of the uniform decrease in perinatal mortality for women of all ages, parities and social classes and not from a diminishing of differences in relative risks which are now virtually identical for a large and growing % of women in Scotland.     

Developmental plasticity and maternal effects of reproductive characteristics in the frog,Bombina orientalis

Summary Life history theory suggests that reproductive characteristics such as ovum size and clutch size should be well buffered against vararies of the environment. However, studies which demonstrate environmental sensitivity of reproductive characteristics are increasing in number, as are studies which find that maternal effects are responsible for much of the variation in developmental and growth rates in embryonic and larval fish and amphibians. The data reported here demonstrate that the environment, in terms of temperature and food availability that a specific individual encounters during vitellogenesis, exerts a strong influence on both egg size and number. Warmer temperatures and less food decrease ovum size, while colder temperatures and less food decrease clutch size. The variation in ovum size that is induced by the environment can exert a strong influence on variation in offspring development and growth and serve as an excellent model for studies on the evolution of developmental plasticity.     

Secondary sex ratios by maternal rank,parity, and age in captive rhesus macaques (Macaca mulatta)

Analysis of 645 conceptions by captive rhesus macaques (Macaca mulatta) with known reproductive histories indicated that maternal age and parity had little effect on the sex of progeny. There was, however, a slight indication that high-ranking females produced a higher proportion of daughters and relatively fewer sons than did low-ranking females. These results provide only weak support for the “advantaged daughter” hypothesis suggested by three previous studies of cercopithecine monkeys, and therefore they further confound the conflicting results for macaques and baboons in general.     

Peptidergic neurohormonal systems in the basal hypothalamus of the ferret and the mink: Immunocytochemical study of variations during the annual reproductive cycle

Summary The hypothalamic systems secreting corticotropin-releasing hormone (CRF), somatostatin, oxytocin, vasopressin and luteinizing hormone-releasing hormone (LHRH) were characterized using immunochemistry, and variations were studied in relation to the recrudescence of testicular activity in the ferret and the mink, two species with opposite photoregulation of their annual reproductive cycles. Under the present conditions of study, the immunoreactivity of the CRF, somatostatin, and oxytocin systems showed no significant variation in either species.In contrast, in these two species, the immunoreactivity of the LHRH system varied considerably depending on the date of observation. The increase in the number and immunoreactivity of the LHRH-secreting neurons that occurred in November in the mink and in January in the ferret, is in agreement with previous results showing that the photoperiod plays an essential role in regulating the annual activity of the testis and that the photoperiodic environmental conditions required for the activation of the LHRH system differ between the species.Similarly, correlations could be found between an increase in immunoreactivity of the vasopressinergic axons projecting to the external median eminence and the recrudescence of testicular activity.     

Influence of age on reproductive performance in the Seychelles warbler

I studied age-related breeding performance of the cooperativelybreeding Seychelles warbler (Acrocephalus sechellensis) on CousinIsland, Seychelles, during 14 years. The annual number of youngthat fledged is significantly related to territory quality andnumber of helpers in the breeding group. Accounting for thesefactors and for the partner's breeding experience, annual productionof fledglings by breeding birds increases from 2 to 5 yearsand decreases beyond 5 years of age. Age-related changes inreproductive success within breeding individuals, paired withthe same experienced partner and occupying the same breedingterritory with similar amount of food from 2 to 8 years of age,show that Seychelles warblers have higher hatching success andproduce more hatchlings and fledglings as they become older.This is probably not a response to decreasing residual reproductivevalue caused by decreasing life expectancy as they become older.Primiparous warblers produce the same number of fledglings asmultiparous warblers of the same age, have a similar life expectancyas multiparous warblers, and occupy territories with similaramounts of resources available for reproduction. As all warblershave similar access to food before reproduction and similarforaging efficiency, the low reproductive success in youngerwarblers cannot be ascribed to differences in environment butto the bird's ability to breed successfully (e.g., a resultof previous helping and/or breeding experience). Effects ofsenescence on reproduction begin to occur from age 6 for bothsexes. From that age, eggs have lower hatching success, butfledging success remains the same. Birds that start breedingat a young age on a given quality territory produce more fledglingsin their lifetime than birds that delay breeding. Many old birdsnever fledge young of their own. They have not been able tobreed because of a shortage of breeding territory vacancies.[BehavEcol 7: 417–425 (1996)]     

Different effects of age on reproductive performance in relation to breeding stage in Bull-headed Shrikes

The difference in the reproductive performance of males and females of the Bull-headed Shrike (Lanius bucephalus) according to age class, i.e. yearling and adult, was studied, and the age-related difference was examined according to parental feeding behavior. The clutch initiation date was not affected by the age class. Females that paired with an adult male laid more eggs per clutch than those paired with a yearling male. The age class of males affected the mass of nestlings at 6 days old, and the age class of females affected the mass of nestlings at 12 days old. The effects of the age of either parent independently were observed at different breeding stages. A change in the degree of nestling feeding peformed by the male and female parents occurred at some point between when the broods were 6 days and 12 days old. It is likely that this caused an effect of age at different stages of the breeding cycle. The effects of the age of the male parent are consistent with accounts of age-related reproduction in raptors where males provide resources to offspring. Individual improvements in foraging skills and/or courtship feeding rate are suggested to be possible explanations. Electronic Publication     

Acetazolamide: maternal toxicity, pattern of malformations, and litter effect

Thirty litters of C57BL 6J mice were administered intraperitoneally one of four doses (0, 500, 750, and 1,000 mg/kg maternal weight) of acetazolamide on day 9 of gestation. The fetuses were removed on day 18 and fixed, stained, cleared, and examined for the pattern of malformations. The forelimb postaxial limb deficiency was the most common abnormality, but forelimb postaxial polydactyly and a postaxial deficiency in the hindlimb were also observed. Males were significantly more likely to be malformed than females at all doses, in contrast to the predominance of females observed in rat fetuses exposed to acetazolamide (Scott et al.: Teratology 6:239-240, '73). The occurrence of limb malformations did not correlate with maternal weight loss, the birth weight of the fetus, or the position of the fetus in the uterus. A "litter effect" was demonstrated in that there was a nonuniform distribution of litters with different proportions of malformed fetuses.     

The influence of age on reproductive performance in the Brown Thornbill

I examined age effects on reproduction in the Brown Thornbill Acanthiza pusilla in Canberra, Australia. I found that the reproductive performance of both males and females improved with age, although only age-related improvement in male performance had a significant effect on annual reproductive success. Reproductive success improved with male age as a result of improved performance during two stages of the breeding cycle: first-year males were less likely to fledge young than those aged two or more, while both first and second-year males were less successful at raising fledglings to independence than males of three or more. Male performance appears to improve over three years as they gain experience at provisioning nestlings and caring for fledglings without attracting predators, rather than as a direct result of improved foraging skills. In contrast, reproductive success only improved slightly with female age, although females of two or more years initiated their first clutch earlier in the season than one-year-old females, and tended to be more likely to re-nest if a breeding attempt failed. The poor performance of young females appears unlikely to be related to their foraging ability but may be associated with costs imposed by dispersing to a breeding vacancy earlier in the year. Although the reproductive performance of Brown Thornbills improves considerably with age I found no evidence that performance improved as a result of repeated breeding attempts with the same partner.     

Presence and distribution of E-cadherin in the 4-cell golden hamster embryo. Effect of maternal age and parity

Maternal age dependency of gestation time in hamster and in other mammals is a well demonstrated fact. We have recently shown that adult nulliparous and multiparous hamster females show significant asynchrony and retard on early embryo development (from two blastomeres to morula stages) when compared with nulliparous young females. The number of cell-cell adhesions between blastomeres in early embryo development has been reported to be a good indication of the ability of embryos to cleave and develop. In this work we studied, by indirect immunofluorescence, the presence and distribution of E-cadherin in 4-cell embryos obtained from nulliparous young (NYF), nulliparous adult (NAF) and multiparous adult (MAF) hamster females. Distribution and intensity of fluorescence was observed and registered using confocal microscopy. Staining intensities for E-cadherin were quantified by computed densitometry in the free membrane regions, in the cytoplasm region and in the cell-cell adhesion zones of each embryo. E-Cadherin in all the studied zones was significantly higher (p<0.01) in NYF. Cadherin concentration in the intercellular membranes was always statistically higher (p<0.05) than in the free membrane regions. An appreciable concentration of E-cadherin was found in the cytoplasm of the 4-cell embryos obtained from the three groups of females, but was significantly higher in NYF. No statistical differences were observed in any of the parameters studied between NAF and MAF. Our results seem to indicate that changes in the reproductive behavior related to age and/or multiparity may be correlated with changes in the processes related to intercellular adhesions during early cleavage.     

The rabbit submandibular gland: sexual dimorphism, effects of gonadectomy, and variations across the female reproductive cycle

Sex differences and the effect of various endocrine conditions on the histology of the rabbit (Oryctolagus cuniculus L.) submandibular (chin) gland were investigated. The female gland contained significantly more acini/field than the male gland. The diameter of acini was significantly smaller than those of the male gland. Gonadectomy reduced the number of acini/field and increased their diameter in females but provoked the opposite effect in males. Gonadectomy drastically reduced the percent of acini with crystal bodies in both sexes, and the percent of acini with apocrine secretion only in females. Estrous does showed a significantly higher number of acini/field than pregnant (days 20 and 29) and lactating (day 6) does. Acini containing crystal bodies declined from 22% in estrous females to 8% and 3% in pre-parturient (gestation day 31) and lactating (day 6) does, respectively. By contrast, acini showing apocrine secretion increased from 12% in estrous females to 43% in pre-parturient does and declined to 23% on lactation day 6. In all glands glycoproteins were noted in crystal bodies but not in apocrine secretion. Results show a sexual dimorphism in the rabbit chin gland histology and support the participation of gonadal steroids in its physiological regulation.Abbreviations GNX gonadectomized - PAS periodic acid Schiff - PASD periodic acid Schiff-diastase     

Effect of maternal age and parity on preimplantation embryo development and transport in the golden hamster (Mesocricetus auratus)

Preimplantation embryo development was studied in the golden hamster (Mesocricetus auratus). Three groups of regularly cycling female hamsters were used: (I) 30 nulliparous young female (NYF) hamsters; (II) 24 nulliparous adult female (NAF) hamsters and (III) 30 multiparous adult female (MAF) hamsters. Female hamsters were mated with male hamsters of proven fertility. Only 15 min were allowed for mating. The moment of ejaculation was registered. Female hamsters were killed from 60 to 69 h after coitus. Corpora lutea were counted in both ovarian surfaces. Oviducts and uterine horns were flushed separately and embryo number, stage of development and distribution were recorded. Adult female hamsters, nulliparous and multiparous, had significant higher ovulation rates than NYF, but their reproductive efficiency was significantly lower. Preimplantation embryo development and transport were highly synchronous in NYF, but not in adults. Morulae were observed in NYF as early as 62-63 h after coitus. In adult female hamsters, significant numbers of morulae were found until 66-67 h. On the contrary, in NYF four-cell embryos were detected only until 60-61 h, while four-cell embryos were found until 64-65 h in NAF, and until 66-67 h in MAF. Embryo transport from the oviduct to the uterus is practically completed at 62-63 h after coitus in NYF, while it is evidently retarded in adult animals. In NYF all eight-cell embryos reached the uterus by 62 h after coitus. In adult female hamsters, both nulliparous and multiparous, a considerable number of eight-cell embryos fail to migrate into the uterus even at 67 h after coitus.