Limitations of Neoseiulus baraki and Proctolaelaps bickleyi as control agents of Aceria guerreronis

Several predatory mites have been found in association with the coconut mite, Aceria guerreronis Keifer, in northeast Brazil. However, the latter still causes damage to coconut in that region. The objectives of this work were to compare the frequencies of occurrence of Neoseiulus (Phytoseiidae) and Proctolaelaps (Melicharidae) species on standing and aborted coconuts in coastal Pernambuco State, northeast Brazil and to analyze their possible limitations as control agents of the coconut mite, based on evaluations of the restrictions they may have to access the microhabitat inhabited by the pest and their functional and reproductive responses to increasing densities of the latter. Neoseiulus baraki (Athias-Henriot) was found mostly on standing coconuts whereas Proctolaelaps bickleyi (Bram) was found mostly on aborted coconuts. Measurements of the entrance to the microhabitat occupied by the coconut mite, between the bracts and the subjacent fruit surface, showed that this different pattern of predator prevalence could be related to predator sizes, although other environmental factors could not be disregarded. Progressively higher predation rate of N. baraki was observed up to an experimental density that corresponded to 1,200 coconut mites per fruit, which is close to the average number determined in northeast Brazil, reducing slightly afterwards. Predation rate of P. bickleyi reduced consistently but slightly with increasing prey densities, but in absolute values, rates were always much higher than determined for N. baraki. The excessively high killing capacity of P. bickleyi, probably related to its high feeding requirement, may be detrimental in terms of stability. In fact, such high requirement for food suggests that P. bickleyi might not have a strong relation with the coconut mite and that the latter may not be its main food source under natural conditions. It is concluded that body sizes of both predators and the exceedingly high feeding requirement of P. bickleyi may limit their performance as control agents of the coconut mite.

Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation

Abstract Background Melatonin is associated with direct or indirect actions upon female reproductive function. However, its effects on sex hormones and steroid receptors during ovulation are not clearly defined. This study aimed to verify whether exposure to long-term melatonin is able to cause reproductive hormonal disturbances as well as their role on sex steroid receptors in the rat ovary, oviduct and uterus during ovulation. Methods Twenty-four adult Wistar rats, 60 days old (+/- 250 g) were randomly divided into two groups. Control group (Co): received 0.9% NaCl 0.3 mL + 95% ethanol 0.04 mL as vehicle; Melatonin-treated group (MEL): received vehicle + melatonin [100 μg/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a.m. Results Melatonin significantly reduced the plasma levels of LH and 17 beta-estradiol, while urinary 6-sulfatoximelatonin (STM) was increased at the morning estrus. In addition, melatonin promoted differential regulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and melatonin receptor (MTR) along the reproductive tissues. In ovary, melatonin induced a down-regulation of ER-alpha and PRB levels. Conversely, it was observed that PRA and MT1R were up-regulated. In oviduct, AR and ER-alpha levels were down-regulated, in contrast to high expression of both PRA and PRB. Finally, the ER-beta and PRB levels were down-regulated in uterus tissue and only MT1R was up-regulated. Conclusions We suggest that melatonin partially suppress the hypothalamus-pituitary-ovarian axis, in addition, it induces differential regulation of sex steroid receptors in the ovary, oviduct and uterus during ovulation.

Genetic Control of Mosquitoes: population suppression strategies

Over the last two decades, morbidity and mortality from malaria and dengue fever among other pathogens are an increasing Public Health problem. The increase in the geographic distribution of vectors is accompanied by the emergence of viruses and diseases in new areas. There are insufficient specific therapeutic drugs available and there are no reliable vaccines for malaria or dengue, although some progress has been achieved, there is still a long way between its development and actual field use. Most mosquito control measures have failed to achieve their goals, mostly because of the mosquito's great reproductive capacity and genomic flexibility. Chemical control is increasingly restricted due to potential human toxicity, mortality in no target organisms, insecticide resistance, and other environmental impacts. Other strategies for mosquito control are desperately needed. The Sterile Insect Technique (SIT) is a species-specific and environmentally benign method for insect population suppression, it is based on mass rearing, radiation mediated sterilization, and release of a large number of male insects. Releasing of Insects carrying a dominant lethal gene (RIDL) offers a solution to many of the drawbacks of traditional SIT that have limited its application in mosquitoes while maintaining its environmentally friendly and species-specific utility. The self-limiting nature of sterile mosquitoes tends to make the issues related to field use of these somewhat less challenging than for self-spreading systems characteristic of population replacement strategies. They also are closer to field use, so might be appropriate to consider first. The prospect of genetic control methods against mosquito vectored human diseases is rapidly becoming a reality, many decisions will need to be made on a national, regional and international level regarding the biosafety, social, cultural and ethical aspects of the use and deployment of these vector control methods.

Gibberellic acid in vegetative and reproductive development of Phalaenopsis orchid hybrid genus

The flower industry represents about one billion dollars in Brazil and the development of techniques aimed at flowering control is required. This study evaluated the influence of gibberellic acid (GA3) on the vegetative and reproductive development of young plants of Phalaenopsis FSNT 'Dai-Itigo' hybrid pink color. The application of GA3 was made by foliar sprays at concentrations of 0, 125, 250, 500 and 1,000 mg L -1. The length of leaves increased significantly when using GA3 at low concentrations, but leaf width decreased. The application of GA3 at 125 mg L -1 showed the best results for the promotion of flowering and flower quality of this orchid hybrid. In this treatment, about 50% of plants treated with GA3 flowered about 6-12 months before the plants that were non-treated with this plant growth regulator. The quality of flowering and flowers was best with 125 mg L -1 GA3.

Neonatally induced mild diabetes: influence on development, behavior and reproductive function of female Wistar rats

Abstract Background Neonatal STZ treatment induces a state of mild hyperglycemia in adult rats that disrupts metabolism and maternal/fetal interactions. The aim of this study was investigate the effect of neonatal STZ treatment on the physical development, behavior, and reproductive function of female Wistar rats from infancy to adulthood. Methods At birth, litters were assigned either to a Control (subcutaneous (s.c.) citrate buffer, n = 10) or STZ group, (streptozotocin (STZ) - 100 mg/kg-sc, n = 6). Blood glucose levels were measured on postnatal days (PND) 35, 84 and 120. In Experiment 1 body weight, length and the appearance of developmental milestones such as eye and vaginal opening were monitored. To assess the relative contribution of the initial and long term effects of STZ treatment this group was subdivided based on blood glucose levels recorded on PND 120: STZ hyperglycemic (between 120 and 300 mg/dl) and STZ normoglycemic (under 120 mg/dl). Behavioral activity was assessed in an open field on PND 21 and 75. In Experiment 2 estrous cyclicity, sexual behavior and circulating gonadotropin, ovarian steroid, and insulin levels were compared between control and STZ-hyperglycemic rats. In all measures the litter was the experimental unit. Parametric data were analyzed using one-way or, where appropriate, two-way ANOVA and significant effects were investigated using Tukey’s post hoc test. Fisher’s exact test was employed when data did not satisfy the assumption of normality e.g. presence of urine and fecal boli on the open field between groups. Statistical significance was set at p < 0.05 for all data. Results As expected neonatal STZ treatment caused hyperglycemia and hypoinsulinemia in adulthood. STZ-treated pups also showed a temporary reduction in growth rate that probably reflected the early loss of circulating insulin. Hyperglycemic rats also exhibited a reduction in locomotor and exploratory behavior in the open field. Mild hyperglycemia did not impair gonadotropin levels or estrous cylicity but ovarian steroid concentrations were altered. Conclusions In female Wistar rats, neonatal STZ treatment impairs growth in infancy and results in mild hyperglycemia/hypoinsulinemia in adulthood that is associated with changes in the response to a novel environment and altered ovarian steroid hormone levels.

Dynamics of cell and tissue genesis in the male reproductive system of ticks (Acari: Ixodidae) Amblyomma cajennense (Fabricius, 1787) and Amblyomma aureolatum (Pallas, 1772): a comparative analysis

Ticks are classified into three families: Argasidae, Ixodidae, and Nutalliellidae. The taxonomy and phylogeny within Ixodidae are still discussed by the specialists, thus requiring further studies. Amblyomma cajennese and Amblyomma aureolatum (Brazil) belong to two species complexes known as “cajennese” and “ovale”, respectively, and are directly related to the transmission of the Brazilian spotted fever. This confirms the medical and veterinary significance of these species, as well as the need for further morphological studies that will bring a better understanding of their taxonomy, phylogeny, and control. In this context, the present study aimed to characterize the morphology of the male reproductive system of A. cajennese and A. aureolatum when unfed and after 4 days of feeding, thereby seeking to: (a) distinguish the two species or “complexes”, and (b) study an internal system which has the potential to be targeted by acaricides. Therefore, males from both species (unfed and after 4 days of feeding) were cold-anesthetized, dissected, and had their reproductive systems removed for histological analysis. The results showed that the morphology of the male reproductive system is generally similar between both species, like in other Ixodidae ticks, exhibiting a multilobed accessory gland complex related to seminal fluid secretion, a pair of vasa deferentia and a pair of testes housing germ cells (spermatocytes) in different stages. The main differences were found in the development of the accessory gland complex cells and germ cells, showing that the maturation of the male reproductive system starts later in A. aureolatum, when compared to A. cajennese. However, during the blood meal, A. aureolatum development is increased, thus making germ cell maturation and gland complex activity higher than in A. cajennese. This study shows the differences in the development of the male reproductive systems of both species, while providing information that can assist in the establishment of new control methods.

Role of Acetylcholine in Control of Sexual Behavior of Male and Female Mammals

The results of studies using systemic or central applications of cholinergic drugs suggest that acetylcholine makes important contributions to the neurochemical control of male- and female-typical reproductive behaviors. In males, cholinergic control seems largely specific to some elements or aspects of copulatory behavior that can vary significantly across species. Synapses in or near the medial preoptic area represent part of this mechanism, but the entire system appears to extend more widely, perhaps especially to one or more structures flanking some part of the lateral ventricle. In females, the lordosis response that essentially defines sexual receptivity is clearly responsive to cholinergic drugs. The same seems likely to be true of other elements of female sexual behavior, but additional studies will be needed to confirm this. Changes in cholinergic activity may help to mediate estrogenic effects on female sexual behavior. However, estrogen exposure can increase or decrease cholinergic effects, suggesting a relationship that is complex and requires further analysis. Also presently unclear is the localization of the cholinergic effects on female sexual responses. Though periventricular sites again have been implicated, their identity is presently unknown. This review discusses these and other aspects of the central cholinergic systems affecting male and female sexual behaviors. Copyright 2014 Elsevier Inc. All rights reserved.

Effect of Parenteral Vitamin E and/or A on Reproductive Performance of Ewes Mated on Pasture or in Drylot

Forty-four Hampshire (H) and 41 Suffolk (S) ewes were allotted within breed to one of four treatment groups (VitA, VitE, VitAE, and Control) to evaluate the effect of supplemental vitamin E and A on reproductive performance of ewes mated on pasture or in drylot. Beginning two weeks before the mating period, ewes received 0 or 300 IU of vitamin E every 14 days and 0 or 250,000 IU of vitamin A every 28 days. Hampshire ewes remained on pasture during the mating period, whereas S ewes were moved to drylot. Treatment did not affect ovulation rate (OR), embryonic loss (EL), fetal loss (FL) or litter size (LS) of H ewes. Embryonic loss was higher (P<.05) in the H yearlings and two-year olds than in older ewes. Litter size was lower (P<.01) for H yearlings compared with other age groups. Suffolk ewes in the VitE group exhibited a lower (P<.01) OR than S ewes in other treatment groups, but no effect of treatment was observed for EL, FL, or LS. Although S yearling ewes did not differ from ewes of other age groups for OR and EL, they did produce fewer (P<.05) lambs. Analysis of serum samples revealed that H yearling ewes exhibited lower (P<.05) serum a-tocopherol levels than older H ewes. In addition, H ewes had a higher (P<.05) serum a-tocopherol level than S ewes at the beginning of study when they were managed as one group. Even though age and breed influenced certain reproductive parameters, results of this study indicate little effect of supplemental vitamin E and A on the overall reproductive efficiency of ewes mated on pasture or in drylot.

Effect of Supplemental Vitamin E and A on Reproductive Performance and Serological Profiles of Ewes Managed in Drylot

Forty Hampshire and 40 Suffolk ewes were allotted to one of four groups (VitA, VitE, VitA&E, Control) in a 2 x 2 factorial treatment arrangement to evaluate the effect of supplemental vitamin E (0 or 300 IU) and vitamin A (0 or 250,000 IU) on reproductive performance. Laparoscopy and ultrasonography were used to measure ovulation rate, embryonic loss, and fetal loss. Serum profiles of a-tocopherol (vitamin E) and retinol (vitamin A) also were monitored. There were no differences (P>.05) among treatment groups in any reproductive trait. Suffolk ewes exhibited a higher (P<.02) ovulation rate than Hampshire ewes, and yearling ewes incurred higher (P<.001) embryonic loss than other age groups, resulting in a lower (P<.001) litter size. Serum levels of a-tocopherol were higher (P<.05) for Hampshire than for Suffolk ewes and were lower (P<.001) in yearling ewes versus ewes two years of age and older. Serum levels of a-tocopherol declined (P<.01) throughout the study in VitA and Control ewes but remained unchanged in VitE and VitA&E ewes. Serum level of retinol remained unchanged in VitA ewes, whereas the level increased (P<.01) initially in VitE, VitA&E, and Control ewes before declining toward initial levels. Correlations were detected between ovulation rate and the change of pre-mating a-tocopherol serum level (r=-.29; P<.02), the change in pre-mating retinol serum level (r=-.50; P<.02) and the interval from vitamin A injection (r=-.60; P<.05). These data indicate significant influences of breed, age, and treatment on a-tocopherol and retinol serum levels in ewes and suggest that the timing of vitamin A administration may influence ovulation rate; however, vitamin supplementation, administered at random stages of the estrous cycle, was unable to alter flock reproductive performance.

Does Immediate Access to Birth Control Help Prevent Pregnancy? A Comparison of Onsite Provision Versus Off Campus Referral for Contraception at Two School-Based Clinics

PURPOSE: The purpose of this study was to assess the impact of different policies on access to hormonal contraception and pregnancy rates at two high school-based clinics. METHODS: Two clinics in high schools (Schools A and B), located in a large urban district in the southwest US, provide primary medical care to enrolled students with parental consent; the majority of whom have no health insurance coverage. The hormonal contraceptive dispensing policy of at School clinic A involves providing barrier, hormonal and emergency contraceptive services on site. School clinic B uses a referral policy that directs students to obtain contraception at an off-campus affiliated family planning clinic. Baseline data (age, race and history of prior pregnancy) on female students seeking hormonal contraception at the two clinics between 9/2008-12/2009 were extracted from an electronic administrative database (AHLERS Integrated System). Data on birth control use and pregnancy tests for each student was then tracked electronically through 3/31/2010. The outcomes measures were accessing hormonal contraception and positive pregnancy tests at any point during or after birth control use were started through 12/2009. The appointment keeping rate for contraceptive services and the overall pregnancy rates were compared between the two schools. In addition the pregnancy rates were compared between the two schools for students with and without a prior history of pregnancy. RESULTS: School clinic A: 79 students sought hormonal contraception; mean age 17.5 years; 68% were > 18 years; 77% were Hispanic; and 20% reported prior pregnancy. The mean duration of the observation period was 13 months (4-19 months). All 79 students received hormonal contraception (65% pill and 35% long acting progestin injection) onsite. During the observation period, the overall pregnancy rate was 6% (5/79); 4.7% (3/63) among students with no prior pregnancy. School clinic B: 40 students sought hormonal contraception; mean age 17.5 years; 52% > 18 years; 88 % were Hispanic; and 7.5% reported prior pregnancy. All 40 students were referred to the affiliated clinic. The mean duration of the observation period was 11.9 months (4-19 months). 50% (20) kept their appointment. Pills were dispensed to 85% (17/20) and 15% (3/20) received long acting progestin injection. The overall pregnancy rate was 20% (8/40); 21.6% (8/37) among students with no prior pregnancy. A significantly higher frequency of students seeking hormonal contraception kept their initial appointment for birth control at the school dispensing onsite contraception compared to the school with a referral policy for contraception (p<0.05). The pregnancy rate was significantly higher for the school with a referral policy for contraception compared to the school with onsite contraceptive services (p< 0.05). The pregnancy rate was also significantly higher for students without a prior history of pregnancy in the school with a referral policy for contraception (21.6%) versus the school with onsite contraceptive services (4.7%) (p< 0.05). CONCLUSION: This preliminary study showed that School clinic B with a referral policy had a lower appointment keeping rate for contraceptive services and a higher pregnancy rate than School clinic A with on-site contraceptive services. An on-site dispensing policy for hormonal contraceptives at high school-based health clinics may be a convenient and effective approach to prevent unintended first and repeat pregnancies among adolescents who seek hormonal contraception. This study has strong implications for reproductive health policy, especially as directed toward high-risk teenage populations.

Developmental effects of estrogen and PCBs in the reproductive tract of BALB/C mice

Many of the tumorigenic effects that result from neonatal exposure to both natural and synthetic estrogens resemble those found in humans exposed to diethylstilbestrol (DES) in utero. Using this established DES neonatal mouse model, my goal was to investigate long-term molecular and morphological effects of certain polychlorinated biphenyls (PCBs) that are weakly estrogenic in adult mice. Focusing on the cervicovaginal (CV) tract, since this is where tumors develop in the BALB/c mouse, I first assessed the 17β-estradiol (E2) dose-response for expression of lactoferrin (LTF). LTF is a highly inducible estrogen biomarker that is permanently altered in uteri from neonatally treated mice. Treatments were administered via 5 subcutaneous injections beginning within 16 hrs after birth, days 1–5. ^ The ontogeny of LTF expression from mouse CV tracts was determined by examining three different stages of life: pups, immature, and mature mice. Northern RNA analysis and immunohistochemistry showed that neonatal E 2 treatment both increases and decreases LTF expression. Early expression of LTF in the CV tract at all doses occurred in pups. In both immature and adult mice, increased LTF expression was dependent on whether E2 induced ovary-dependent or ovary-independent persistent vaginal cornification. ^ Next, I studied biological responses from neonatally PCB exposed adult mice. As expected, using a neonatal uterine bioassay I showed that 2 ′4′6′-trichloro-4-biphenylol (OH-PCB-30), 2′3′4′ 5-tetrachloro-4-biphenyloI (OH-PCB-61), and OH-PCB-30/61 (50/50 mixture), were estrogenic causing a dose-dependent increase in uterine weight. ^ Long-term effects of OH-PCB 30 [200 μg/pup/day] were most similar to E2 as seen by an increased uterine wet weight in day 50 mice similar to E2 [5 μg/pup/day] (141% and 140% of control, respectively). Another similarity between OH-PCB 30 and E2 neonatally treated mice was found in those sacrificed at 20 months of age. At these same doses CV tract squamous cell carcinoma induction was 43% of E2 treated mice and 47% of OH-PCB 30 treated mice. Differences were noted in adenoaquamous; cell carcinoma development, where 16% of OH-PCB-30 neonatally treated mice developed tumors versus 8% for E2. Based on these results using the neonatal mouse model, I conclude that the OH-PCBs tested are strongly estrogenic and tumorigenic showing dose-response relationships when exposure occurs during development of the reproductive tract in mice. These results may have important implications for risk assessment in determining the effects of xenoestrogens exposure early versus later in life. ^

Simulation of the Impact of Dams and Fishing Weirs on Reproductive Potential of Silver-Phase American Eels in the Kennebec River Basin, Maine

I modeled the cumulative impact of hydroelectric projects with and without commercial fishing weirs and water-control dams on the production, survival to the sea, and potential fecundity of migrating female silver-phase American eels, Anguilla rostrata in the Kennebec River basin, Maine, This river basin has 22 hydroelectric projects, 73 water-control dams, and 15 commercial fishing weir sites. The modeled area included an 8,324 km(2) segment of the drainage area between Merrymeeting Bay and the upper limit of American eel distribution in the basin. One set of input,, (assumed or real values) concerned population structure (Le., population density and sex ratio changes throughout the basin, female length-class distribution, and drainage area between dams), Another set concerned factors influencing survival and potential fecundity of migrating American eels (i.e., pathway sequences through projects, survival rate per project by length-class. and length-fecundity relationship). Under baseline conditions about 402,400 simulated silver female American eels would be produced annually reductions in their numbers due to dams and weirs would reduce the realized fecundity (i.e., the number of eggs produced by all females that survived the migration). Without weirs or water-control dams, about 63% of the simulated silverphase American eels survived their freshwater spawning migration run to the sea when the survival rate at each hydroelectric dam was 9017, 40% survived at 80% survival per dam, and 18% survived at 60% survival per dam. Removing the lowermost hydroelectric dam on the Kennebec River increased survival by 6.0-7.6% for the basin. The efficient commercial weirs reduced survival to the sea to 69-76%( of what it would have been without weirs', regardless of survival rates at hydroelectric dams. Water-control dams had little impact on production in this basin because most were located in the upper reaches of tributaries. Sensitivity analysis led to the conclusion that small changes in population density and female length distribution had greater effects on survival and realized fecundity than similar changes in turbine survival rate. The latter became more important as turbine survival rate decreased. Therefore, it might be more fruitful to determine population distribution in basins of interest than to determine mortality rate at each hydroelectric project.

Antioxidants improve vascular function in children conceived by assisted reproductive technologies: A randomized double-blind placebo-controlled trial.

AIMS Children conceived by assisted reproductive technology (ART) display vascular dysfunction. Its underlying mechanism, potential reversibility and long-term consequences for cardiovascular risk are unknown. In mice, ART induces arterial hypertension and shortens the life span. These problems are related to decreased vascular endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. The aim of this study was to determine whether ART-induced vascular dysfunction in humans is related to a similar mechanism and potentially reversible. To this end we tested whether antioxidants improve endothelial function by scavenging free radicals and increasing NO bioavailability. METHODS AND RESULTS In this prospective double-blind placebo controlled study in 21 ART and 21 control children we assessed the effects of a four-week oral supplementation with antioxidant vitamins C (1 g) and E (400 IU) or placebo (allocation ratio 2:1) on flow-mediated vasodilation (FMD) of the brachial artery and pulmonary artery pressure (echocardiography) during high-altitude exposure (3454 m), a manoeuver known to facilitate the detection of pulmonary vascular dysfunction and to decrease NO bioavailability by stimulating oxidative stress. Antioxidant supplementation significantly increased plasma NO measured by ozone-based chemiluminescence (from 21.7 ± 7.9 to 26.9 ± 7.6 µM, p = 0.04) and FMD (from 7.0 ± 2.1 to 8.7 ± 2.0%, p = 0.004) and attenuated altitude-induced pulmonary hypertension (from 33 ± 8 to 28 ± 6 mm Hg, p = 0.028) in ART children, whereas it had no detectable effect in control children. CONCLUSIONS Antioxidant administration to ART children improved NO bioavailability and vascular responsiveness in the systemic and pulmonary circulation. Collectively, these findings indicate that in young individuals ART-induced vascular dysfunction is subject to redox regulation and reversible.

Right ventricular dysfunction in children and adolescents conceived by assisted reproductive technologies.

Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity.

Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.