Fetal Sex Ratio Research Articles

Fetal Sex Ratios in Southwestern Montana Elk

ABSTRACT The Trivers‐Willard (1973) model suggests maternal control of offspring sex, in utero or by the end of parental investment, may be an adaptive advantage in some species. We tested for differential sex allocation using 11,408 known‐sex fetal elk (Cervus elaphus) from biological collections and hunter harvest returns from 2 southwestern Montana, USA, elk populations (1961–2007). We included maternal and environmental condition covariates measured pre‐ and postconception and throughout pregnancy. Results suggested that adult female elk in southwest Montana did not differentially invest in male offspring when conditions were beneficial. We found evidence that, when the Northern Yellowstone elk herd was at low density, beneficial spring (May‐Jun) growing conditions, as indexed by a local precipitation measure and a regional drought indicator, correlated with production of more female fetuses (1 SD increase in precipitation and 1 SD decrease in drought resulted in 6% and 5% more F fetuses, respectively). In the same herd, we found evidence that improved maternal condition, as indexed by kidney fat mass and heart fat mass, also correlated with production of more female fetuses (1 SD increase in kidney fat mass and heart fat mass resulted in 8% more F fetuses). When the same elk herd reached higher densities under different ecological conditions, no covariate was associated with a deviation in the 50:50 female‐to‐male sex ratio. Similarly, there was no association between covariates and fetal sex ratios in a nearby elk herd at high population density. In modeling, wildlife managers should consider factors that could alter sex ratios at birth, and also how biased sex ratios postpartum could affect population models.

Association Between Fetal Sex Ratio And Maternal Eclampsia - A Descriptive Study In Pakistani Population

Background Different maternal conditions like diabetes, abruptio placentae and preterm labour and even eclampsia has been linked to fetal gender with conflicting results.Objective To study any association between maternal eclampsia and fetal sex ratio.Setting. Department of Obstetrics & Gynaecology, Sir Ganga Ram Hospital, Lahore.Methods The data was collected from hospital records of seven years from 2001-2007.Sex ratio was defined as number of males per 100 females.Results Results revealed male to female sex ratio 1.06 (95% CI 1.05-1.06) in non-eclamptic births and 1.77 (95% CI 1.120-2.086) in births complicated with eclampsia. Women with eclampsia had increased fetal male sex ratio (1.77). The proportion of male births (60.22 %) was statistically significant (p<.05) from proportion of males in non-eclamptic births (51.49 %). The calculated p value by chi sq was 0.02.Conclusion We found meaningful association between male fetal gender and maternal eclampsia. Those pregnancies where the fetus is male in our region, may require appropriate monitoring and timely intervention to achieve an optimal outcome. Carrying a male fetus may be regarded as having a higher risk for development of eclampsia. Preventive measures can be taken early in pregnancy include offering ultrasound for detection of fetal sex, aspirin prophylaxis and Doppler studies.

Reproductive and demographic parameters in two Iberian wild boarSus scrofa populations

From 1990 to 2006, we studied the demographic, reproductive, and biometric characteristics of two Iberian wild boarSus scrofa (Linnaeus, 1758) populations in contrasting environments. In the Pyrenees (studied in 1990–1993), forest cover is high, hunting pressure is low, and the density of wild boar is high. In the Ebro Valley (studied in 1994–2006), there are few shelter areas for boars, hunting pressure is high, and density is very low. In the second semester of life and after two years of age, the sows in Ebro Valley were heavier than were those in the Pyrenees. Pregnancy during the first year of life was frequent in the Ebro Valley and rare in the Pyrenees. Litter sizes, ovulation rates, and intrauterine mortalities did not differ significantly between the two populations, but the foetal sex ratio in the Ebro Valley was skewed significantly towards males. Life expectancy was lower in the Ebro Valley (6 yr) than it was in the Pyrenees (10 yr). In the Ebro Valley 75% of the wild boar were >24 months old, whereas in the Pyrenees, the proportion was 59%. We suggest that shelter availability influenced the growth, productivity, hunting pressure, and life expectancy in the two Iberian populations of wild boar.

Comparison of embryo yield and pregnancy rate between in vivo and in vitro methods in the same Nelore ( Bos indicus) donor cows

To investigate why the preferred means to produce bovine embryos in Brazil has changed from in vivo to in vitro, we compared these two approaches in the same Nelore cows ( n = 30) and assessed total embryo production and pregnancy rates. Without a specific schedule, all cows were subjected to ultrasound-guided ovum pick up (OPU)/ in vitro production (IVP) and MOET, with intervals ranging from 15 to 45 d between procedures, respectively. To produce in vivo embryos, cows were superovulated and embryos were recovered nonsurgically from 1 to 3 times (1.4 ± 0.6), whereas OPU/IVP was repeated from 1 to 5 times (3.2 ± 1.2) in each donor cow during a 12-mo interval. Embryos obtained from both methods were transferred to crossbred heifers. On average, 25.6 ± 15.3 immature oocytes were collected per OPU attempt. The average number of embryos produced by OPU/IVP (9.4 ± 5.3) was higher ( P < 0.05) than the MOET method (6.7 ± 3.7). However, pregnancy rates were lower ( P < 0.05) following transfer of IVP (33.5%) versus in vivo-derived embryos (41.5%) embryos. Embryonic losses between Days 30 and 60 and fetal sex ratio were similar ( P > 0.05) between in vivo and in vitro-derived embryos. We concluded that in Nelore cows, with an interval of 15 d between OPU procedures, it was possible to produce more embryos and pregnancies compared to conventional MOET.

Studies of the Toxicological Potential of Capsinoids: IX. Teratology Studies of Dihydrocapsiate in Rats and Rabbits

In order to determine the safety of dihydrocapsiate (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS no. 205687-03-2), teratology studies were conducted in pregnant Sprague-Dawley rats (18 to 20 animals per group) and pregnant New Zealand white rabbits (20 to 21 animals per group). The test substance was administered by gavage for 11 days, from days 7 to 17 of gestation in rats, and for 13 days from days 6 to 18 of gestation in rabbits, at dose levels of 0 (vehicle), 100, 300, or 1000 mg/kg/day. In the rat study, no deaths occurred in any group and there were no test substance-related changes or abnormalities in clinical signs, body weight, food consumption, or gross pathological findings. There were no test substance-related changes in the number of corpora lutea, number of implantations, index of implantations, index of embryofetal deaths, and number, sex ratio, or body weight of live fetuses at the end of the gestation period and there were no abnormalities in the placentae of live fetuses. There were no test substance-related abnormalities or variations in the external, skeletal, or visceral examinations of live fetuses. There were no abnormalities in ossification. En toto, it was concluded there were no teratogenic effects in the rat study. In the rabbit study, there were no test substance-related effects on clinical signs, body weight, food consumption, or necropsy findings in any group. There were neither test substance-related abortions nor test substance-related effects on the number of corpora lutea, number of implantations, or implantation index in any group. There were no test substance-related effects on the number of dead embryos/fetuses, the number, sex ratio, or body weight of live fetuses, or gross pathological finding of placentae. There were no test substance-related external abnormalities, or incidence of visceral or skeletal abnormalities or variations, and there were no test substance-related effects on the progress of ossification in any group. Based upon these data, the no observed adverse effect level (NOAEL) of dihydrocapsiate for general toxicity in dams, reproductive functions of dams, and embryofetal development was judged to be 1000 mg/kg/day both in rats and rabbits.

Ultrasonographic Study of Deep Portion of Diencephalo‐Telencephalic Vesicle for the Determination of Gestational Age of the Canine Foetus

The aim of this study was to evaluate the accuracy of ultrasonographic measurement of the deep portion of diencephalo-telencephalic vesicle (DPTV) in the prediction of delivery date in different size bitches. The effects of litter size and foetal sex ratio on the accuracy were also investigated. For this purpose, the growth curve of DPTV was derived in large size dogs (26-40 kg) and the results of the accuracy of the prediction were compared with those obtained in small (< or =10 kg) and medium (11-25 kg) size dogs by the application of the equations derived from the growth curve previously described. Ultrasonographic examinations were performed once a week during the second half of pregnancy in seven large size bitches (26-40 kg body weight). A linear regression model was adopted to analyse the relationship between the DPTV mean values and the days remaining to parturition. The results of regression analysis indicated that DPTV measurement in large size dogs is significantly and linearly related to the gestational age. Ultrasonographic measurements of DPTV were also performed during pregnancy in different size bitches with unknown breeding dates. Although the results indicated a similar accuracy of the prediction of the date of parturition in the different sizes of bitches, a higher accuracy was obtained in normal and large litter size compared with small litters. Foetal sex ratio did not affect the accuracy. In conclusion, this study demonstrated that the accuracy of the prediction of parturition day obtained by ultrasonographic evaluation of DPTV growth is reliable when specific formulae for different size dogs are applied. It should be noted that although foetal sex ratio does not affect the accuracy, the prediction could be less accurate when a small litter is present.

Adjustment of Reproductive Investment and Offspring Sex Ratio in White-tailed Deer (Odocoileus virginianus) in Relation to Winter Severity

Both density-dependent factors and environmental stochasticity can impact the dynamics of free-ranging populations. The pathways through which these factors influence population dynamics can be complex and may be immediate or lagged, and cumulative effects of environmental factors have been reported. We examined the effects of the severity (snow depth and persistence and winter rainfall) of the current and previous winters on the probability that female adult and yearling white-tailed deer (Odocoileus virginianus) would produce a fetus, and that adult females would produce a male fetus. We used logistic regression and Akaike’s information criterion to select the best models from a set of 11 a priori candidate models. The severity of the winter 1 year before gestation negatively impacted the probability that both adults and yearlings would produce a fetus. There was no evidence that the probability of yearlings or adults producing a fetus was affected by winter conditions while gestating. Further, there was no evidence that the severity of the winter during which a yearling was gestated affected its probability of producing a fetus as a yearling. As the severity of the winter of gestation increased, the probability of producing a male decreased, consistent with both the Trivers‐Willard sex ratio adjustment hypothesis and the extrinsic modification hypothesis. We suggest that both the decreased probability of reproduction after severe winters and the variation in fetal sex ratio may ultimately increase lifetime fitness if they lead to the production of the fittest offspring given the available maternal resources.

Developmental toxicity and uterotrophic studies with di‐2‐ethylhexyl terephthalate

These studies were conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) exposure on in utero development in mice and rats. In addition, a uterotrophic assay for estrogenic activity was conducted in sexually immature rats. In the developmental toxicity studies, diet containing DEHT was fed to four groups of mated female Crl:CD(SD)IGS BR rats (25/group) from gestation day (GD) 0-20 or Crl:CD1(ICR) mice (25/group) from GD 0-18. Concentrations within the feed were 0, 0.3, 0.6, and 1.0% for the rats and 0, 0.1, 0.3, and 0.7% for the mice. Laparohysterectomies were carried out on the last day of exposure and the numbers of fetuses, early and late resorptions, total implantations, and corpora lutea were recorded. The fetuses were weighed, sexed, and examined for external, visceral and skeletal malformations, and developmental variations. The dose rate from dietary DEHT exposure was 0, 226, 458, and 747 mg/kg/day in the rats and 197, 592, and 1382 mg/kg/day in the mice for the control, low, mid, and high-exposure groups, respectively. DEHT exposure did not affect clinical observations. A slight reduction in body weight gain was noted in the high-dose level rat group; the remaining groups were unaffected. At necropsy, increased liver weights were noted in the high-dose rat group and the mid- and high-dose mouse groups. Mean numbers of implantation sites and viable fetuses, mean fetal weights, and mean litter proportions of preimplantation loss, early resorptions, late resorptions, and fetal sex ratios were unaffected by DEHT exposures. No test article-related malformations or variations were observed at any concentration level in the rat and mouse developmental toxicity studies. In the uterotrophic assay for estrogenic activity, sexually immature female rats received oral gavage doses 20, 200, or 2000 mg DEHT/kg bw/day from postnatal day (PND) 19-21. A slight reduction in rate of body weight gain was noted on the first day of dosing in the high dose group, but no other indications of toxicity were evident. DEHT exposure did not affect wet or blotted uterine weight parameters in any of these dose groups. The NOEL for developmental toxicity in rats was 747 mg/kg/day and 1382 mg/kg/day in mice. The NOEL for estrogenic activity was 2000 mg/kg/day. The NOEL for maternal toxicity was 458 mg/kg/day in rats and 197 mg/kg/day in mice. The lack of adverse developmental effects with DEHT exposure are in contrast to the adverse developmental effects noted after di-2-ethylhexyl phthalate (DEHP) exposure. The difference between the effects noted with the ortho-constituent (DEHP) and the lack of effects reported with the para-constituent (DEHT) is due most likely to differences in metabolism and the formation of the stable monoester, mono-2-ethylhexyl phthalate (MEHP) from the DEHP moiety.

Shift in the Sexes: Are Endocrine Disruptors Changing Birth Ratios?

According to demographic data compiled by the United Nations, an average of 105 boys are born for every 100 girls. The male proportion of births, equal to 0.515, varies slightly between years and populations, but these factors do not fully explain consistently shifting ratios in several industrialized countries over recent decades. A new study examines birth and fetal death sex ratios in Japan and the United States and reveals significant male-to-female shifts in both nations [EHP 115:941–946; Davis et al.]. The research team calculated birth and fetal death sex ratios in Japan based on 1949–1999 data from the Japanese Vital Statistics Bureau. The proportion of male births varied yearly before 1970 but declined steadily since then, from 0.5172 to 0.5135. Between 1960 and 1999, the male proportion of fetal deaths increased from 56% to 67.7%. The male fetal death rate is approximately four times higher in Japan than in the United States. For U.S. calculations, the researchers drew 1983–1995 fetal death data and 1970–2002 birth data from the National Center for Health Statistics. The proportion of male births dropped in the United States, from 0.5134 in 1970 to 0.5117 in 2002. There are significant racial differences, however: between 1970 and 2002 the proportion of non-Hispanic white male births fell from 0.5143 to 0.5122, whereas the proportion of black male births rose slightly from 0.5076 to 0.5079. The male proportion of black fetal deaths also increased, rising from 53.5% to 54.5%; among whites, the male proportion of fetal deaths rose by less than 0.5%. Why birth sex ratios differ so much between white and black women is unknown, but hormonal differences due to race and to incidence of obesity may be involved. A possible explanation for the increased ratio among black births may stem from improved prenatal and obstetric care in general, reducing the overall number of fetal deaths. The researchers speculate that parental exposures to endocrine-disrupting chemicals, including metalloestrogens such as methylmercury, might be factors undermining the conception and survival of male children. They suggest particular scrutiny of Japanese body burden of mercury and other metalloestrogens to understand this difference. Additionally, future investigations of declining sex ratios should consider the types and timing of prenatal and parental exposures to endocrine-disrupting chemicals. The researchers hypothesize that paternal exposures prior to conception might affect expression of the SRY gene on the Y chromosome.

Progeny Sex Ratio in a Sexually Monomorphic Ungulate, the Collared Peccary (Tayassu tajacu)

Polygynous ungulates are commonly used to test the Trivers–Willard hypothesis that high-quality females should produce a higher proportion of male than female offspring given certain assumptions. We studied relationships among age, maternal condition, and sex ratio of progeny in the collared peccary (Pecari tajacu), a sexually monomorphic ungulate, in southern Texas to examine this hypothesis. We collected data on litter size and sex ratio from 264 peccaries from 1989 to 2003. The overall fetal sex ratio was male-biased (P ¼ 0.04) at 54.8% male. Sex ratio varied by age, with individuals in age class 2 (of 4) being responsible for most of the skew in the ratio. Condition indices (body mass, carcass mass, and kidney fat index) did not vary in females categorized by sex ratio of litters. Logistic regression revealed that increasing condition of peccaries was associated with a more male-biased litter, but these relationships were weak (P ¼ 0.10–0.20). Our results were consistent with recent work showing sex ratio–age relationships and reviews documenting decreasing support for the Trivers–Willard hypothesis in ungulates with less sexual dimorphism.

Litter size and fetal sex ratio adjustment in a highly polytocous species: the wild boar

For species in which reproductive success is more variable in one sex than the other, the Trivers and Willard model (TWM) predicts that females are able to adjust their offspring sex ratio. High-quality mothers should provide greater investment to one sex than the other. Previous tests of the TWM have been inconsistent, and whether the TWM applies to species with several offspring per litter is unclear due to possible trade-offs between size, number, and sex of the offspring. Williams’ model (WM) accounts for confounding effects of these trade-offs on sex ratio variation. Lastly, the ‘‘extrinsic modification hypothesis’’ predicts changes in offspring sex ratio in relation to climatic conditions and population density. Using wild boar as a model, we tested 1) whether the WM fitted observed sex ratio variation and 2) whether sex ratio variations were related to maternal attributes (test of the TWM) and/or to resource availability (test of the extrinsic modification hypothesis). Females adjusted their litter size rather than their litter composition, so that the WM was not supported. Likewise, changes in resource availability did not influence the fetal sex ratio, so that the extrinsic modification hypothesis was not supported. The fetal sex ratio was negatively related to increasing litter size, providing some support for the TWM. Sex ratio was male biased for litter sizes up to 6 and then became female biased in larger litters. Our results provide the first case study showing marked changes in sex ratio in relation to litter size in a large mammal. Key words: litter size, primary sex ratio, sex ratio variation, Sus scrofa scrofa, Trivers and Willard model, Williams model. [Behav Ecol]

A new pair of primers for molecular sexing of the Pallas squirrel, Callosciurus erythraeus, and variation in fetal sex ratio

The Pallas squirrel, Callosciurus erythraeus, is an introduced species to Japan where a male-biased sex ratio has been reported at the weaning stage in the field. For further examination of their earlier (fetal) sex ratio, a new PCR primer set was designed to amplify a portion of the Sry (sex-determining region Y) gene. This successfully produced sex-specific PCR profiles for known-sex adult samples. Using this technique we could determine the sex of fetal samples dissected out of mothers shot as pests on Izu-Oshima Island, Tokyo, Japan. The fetal sex ratio was significantly male-biased in 2000, but not in other years. The sex ratio tending towards male-bias in this squirrel is discussed from a local resource competition theory.

OC6 Scrotal Heat Stress in Mice Affects Viability and DNA Integrity of Sperm, and Sex Ratio of the Offspring

Heat stress causes infertility in farm animals and represents a major source of economic loss. The objective of this work was to examine the impact of scrotal heat stress (42°C for 30 min) on viability of spermatozoa, integrity of their DNA, and the in vivo reproductive performance of CD1 mice. These parameters were assessed in the spermatozoa recovered from epididymis at 0, 7, 14, 21 and 28 days after heat treatment. Heat stressed males were mated with CD1 females, and the number and the sex ratio of Day14 fetuses was analyzed by PCR. Heat stress increases the percentage of TUNEL positive sperm present in the epididymis at the time of heating (Day 0 and 7). Also the damage was significantly higher than the control at Day 14, 21 and 28 indicating that some germ cells, which were present within the testis at the time of heat stress, were not removed by apoptosis and completed their development producing sperm with damaged DNA. Heat stress also affects viability and motility at Day 14, 21 and 28. When the sex ratio of the offspring of the males mated the Day 0 or 7 after the heat stress was assessed, we observed that the percentage of males was significantly lower than expected (p &lt; 0.05). No differences were observed in the sex ratio of the offspring of the other groups. In conclusion, these data demonstrate that the increase in epididymal temperature can compromise the DNA integrity of spermatozoa and the sex ratio of offspring generated with this sperm, and suggest that spermatocytes are most vulnerable than spermatids to DNA damage induced by heat stress.

Developmental toxicity of dibutyltin dichloride in cynomolgus monkeys

Dibutyltin dichloride (DBTCl) has been shown to be teratogenic in rats. The present study was conducted to determine the teratogenic potential of DBTCl given to pregnant monkeys during the entire period of organogenesis. Cynomolgus monkeys were dosed once daily by nasogastric intubation with DBTCl at 0, 2.5 or 3.8 mg/kg on days 20–50 of pregnancy, the whole period of organogenesis. The pregnancy outcome was determined on day 100 of pregnancy. In both DBTCl-treated groups, a significant increase in the incidence of pregnant females with soft stool and/or diarrhea, and with yellowish stool was observed. Maternal body weight gain at 3.8 mg/kg and food consumption at 2.5 and 3.8 mg/kg were decreased during the administration period. The survival rate of fetuses at terminal cesarean sectioning was decreased in the DBTCl-treated groups and significantly decreased at 2.5 mg/kg. There were no changes in the developmental parameters of surviving fetuses, including fetal body weight, crown-rump length, tail length, sex ratio, anogenital distance and placental weight, in the DBTCl-treated groups. No external, internal or skeletal malformations were found in the fetuses in any group. Although internal and skeletal variations were found, no difference in the incidence of fetal variation was noted between the control and DBTCl-treated groups. No effect on skeletal ossification was observed in fetuses in the DBTCl-treated groups. The data demonstrate that DBTCl is embryolethal but not teratogenic in cynomolgus monkeys.

Comparison of the accuracy of two ultrasonographic measurements in predicting the parturition date in the bitch

To compare the accuracy of two ultrasonographic measurements, inner chorionic cavity diameter and biparietal diameter, for the prediction of parturition date in small and medium size bitches. The effects of litter size and fetal sex ratio on the accuracy of the prediction were also investigated. Ultrasonographic examinations were performed on pregnant bitches and, depending on the stage of pregnancy, the inner chorionic cavity diameter and biparietal diameter were measured. The mean value of the data of each structure was calculated and the predicted day of parturition was obtained by the application of equations derived from growth curves we previously developed for different size bitches. The parturition term was predicted with similar accuracy during early gestation, by the measurement of inner chorionic cavity diameter, as well as during late gestation, by the measurement of biparietal diameter. Litter size affected only biparietal diameter accuracy, whereas fetal sex ratio did not influence the estimation of the day of parturition. Inner chorionic cavity diameter and biparietal diameter were equally reliable parameters in obtaining a reasonably accurate prediction of parturition date at any gestational period at which a bitch is examined.

Aggression and anxiety in pregnant mice are modulated by offspring characteristics

We investigated aggressiveness and anxiety during late pregnancy in mice, Mus domesticus in relation to the pups' characteristics. The female's aggressive behaviour towards a male intruder and behavioural anxiety were evaluated in separate experiments during late pregnancy (days 17–18) and individual scores were correlated with the number and sex of the delivered pups. We did a preliminary experiment to compare the behavioural measures of anxiety in the classical elevated plus-maze test and in a new experimental condition designed for pregnant females (three-compartment test choice: clean, own and unknown male's bedding): the time spent in the male's compartment by pregnant females was negatively correlated with the percentage of entries and time spent in the open arms of an elevated plus-maze. This allowed us to measure anxiety twice in the same female: in dioestrus and during pregnancy. Females' anxiety increased during late pregnancy and no significant correlation was observed between individual scores. Aggressive behaviour and anxiety were affected by the number of pups the pregnant female was carrying: the larger the litter, the more aggressive and more anxious the female was towards a male's cues. By contrast, the offspring fetal sex ratio did not affect the amount of aggressive behaviour and the level of anxiety shown by the mothers to be.

The fetal sex ratio and metabolic, biochemical, haematological and clinical indicators of severity of hyperemesis gravidarum

The association between female fetal sex and hyperemesis gravidarum is well established in European and North American populations. The association between female fetuses and severity of hyperemesis remains uncertain. A retrospective study based on case notes review of 166 Asian women hospitalised for hyperemesis was performed. Female fetuses were significantly associated with hyperemesis in our population (P= 0.004, OR 1.6, 95% CI 1.2-2.2) as well as associated with severe ketonuria and high urea. When both severe ketonuria and high urea were present at initial hospital admission for hyperemesis, 83% (95% CI 66-93) of the fetuses were female.

Evaluation of Developmental Toxicity of Ultraviolet Absorber 2-(3′,5′-Di-tert-Butyl-2′-hydroxyphenyl)-5-Chlorobenzotriazole in Rats

2-(3′,5′-Di-tert-butyl-2′-hydroxyphenyl)-5-chlorobenzotriazole (DBHCB) is widely used as a UV absorber. In this study, the developmental toxicity of DBHCB was evaluated in rats. Pregnant rats were given DBHCB at 0, 62.5, 250, or 1000 mg kg−1 day−1 by gavage on days 5–19 of pregnancy. No deaths were observed in the pregnant rats of any group. No effect of DBHCB on the general conditions, body weight gain, or feed consumption was observed in the pregnant rats. There were no changes in the ovarian weight, gravid uterine weight, or necropsy findings in the maternal rats of the DBHCB-treated groups. No significant effects of DBHCB were found in the number of corpora lutea, implantations, live fetuses, resorptions or dead fetuses, incidence of pre- or postimplantation embryonic loss, viability of fetuses, fetal weight, or sex ratio of live fetuses. No significant difference in the incidence of fetuses with malformations or variations or degree of ossification was detected between the DBHCB-treated and control groups.

Studies of the Toxicological Potential of Tripeptides (L-Valyl-L-prolyl-L-proline and L-lsoleucyl-L-prolyl-L-proline): VI. Effects of Lactobacillus helveticus-fermented Milk Powder on Fertility and Reproductive Performance of Rats

The objective of these studies was to assess the effects of the tripeptides, L-valyl-L-prolyl-L-proline (VPP) and L-isoleucyl-L-prolyl-L-proline (IPP), on reproductive capabilities of male and female rats. The specific goals of the experiments were (1) to determine the effects of orally administered tripeptides on (a) fertility and reproductive behavior in both sexes of rats, (b) embryo-fetal development in pregnant rats, and (c) pre- and postnatal development of rats exposed to tripeptides in utero and during lactation; and (2) to estimate the no-observable-adverse-effect doses of tripeptides in maternal and fetal rats. During the conduct of these classical segment I, II, and III studies, the test material was powdered Lactobacillus helveticus-fermented milk (FM), which contains the tripeptides, VPP and IPP. FM (0, 500, 1000 or 2000 mg/kg body weight [BW]/day--equivalent to 0, 0.8, 1.6, or 3.3 mg/kg BW/day of VPP plus IPP) was administered to males by oral gavage from 4 weeks prior to mating until sacrifice, and to females from 2 weeks prior to mating through day 20 of lactation. Evaluative parameters included monitoring grossly observable clinical signs; food consumption and body weight gains; mating behavior and fertility indices of both sexes; implantation and maintenance of embryos; sex ratio of live pups; fetal viability; incidences of external, visceral or skeletal variations; growth and behavioral development; as well as reproductive capabilities of F1 offspring exposed to FM during gestation and lactation. All animals were subjected to macroscopic examination at termination of their segment of the studies. Clinical signs, body weights, and food consumption were unaffected by administration of FM. During segment I, the test agent had no effect on estrus cycle, mating behavior, fertility index, or reproductive competence of either males or females. The results of segment II experiments revealed no effects of FM on postimplantation survival-loss, sex ratio or birth weights of live fetuses, and there was no evidence of treatment-associated developmental or teratological effects. During segment III, FM was without effect on pup viability, behavioral and sexual maturation, and reproductive capability of the F1 generation. Under the conditions of these experiments, the no-observable-adverse-effect level (NOAEL) of FM on reproductive performance in male and female rats is greater than 2000 mg/kg BW/day, the equivalent of 3.3 mg/kg BW/day of VPP plus IPP.

Sex ratios in California following the terrorist attacks of September 11, 2001

Natural and man-made disasters as well as declining economies appear to coincide with reduced odds of male live births among humans (i.e. lower secondary sex ratio). This association has been attributed to excess death of males in gestation and to reduced conception of males. We attempt to empirically discriminate between these two attributions by testing the hypotheses that the attacks of September 11, 2001 were followed in California first by higher fetal death sex ratios and later by lower sex ratios among very low weight births and total live births. We apply interrupted time-series methods to the fetal death, very low birth weight, and secondary sex ratios. The methods control for trends, seasonal cycles, and other forms of autocorrelation that could induce spurious associations. Findings support the excess death explanation in that the fetal death sex ratio reached its highest level in the 6 year test period in October and November of 2001, while the very low weight birth sex ratio dropped to its lowest level in 14 years in December of 2001. The secondary sex ratio exhibited its second lowest value in 14 years in December of 2001. No support was found for the reduced conception explanation in that the sex ratio did not differ from expected values 9, 10 or 11 months after the attacks. We infer support for the excess death explanation at the expense of the reduced conception explanation. We also describe the implications of our findings for public health planning.