Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates

Minamoto, Toshiko; Nakayama, Kentaro; Ishibashi, Tatsuro; Ishikawa, Masatoshi; Nakamura, Kazuto; Yamashita, Hiroyuki; Shanta, Kamrunnahar; Hossain, Mohammad Mahmud; Sultana, Rehena; Iida, Kouji; Sakashita, Gyosuke; Nakamura, Tsukasa; Kanda, Hideyuki; Kyo, Satoru

doi:10.3390/ijms21249688

Cited by 6 publications

(3 citation statements)

References 47 publications

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“…Several authors suggested telomere shortening as a potential mechanistic mediator not just of ageing and age-related diseases, but also of fetal programming [40]. Certain circumstances, such as psychosocial stress of the mother during pregnancy [41], conception after assisted reproductive technology [42] or intrauterine stress exposure, are associated with the length of offspring telomeres [43]. If mothers have the metabolic syndrome during pregnancy, it is associated with 14% shorter child telomeres compared with control children [44].…”

Section: Discussionmentioning

confidence: 99%

Diabetic pregnancy as a novel risk factor for cardiac dysfunction in the offspring—the heart as a target for fetal programming in rats

et al. 2021

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Aims/hypothesis The impact of diabetic pregnancy has been investigated extensively regarding offspring metabolism; however, little is known about the influence on the heart. We aimed to characterise the effects of a diabetic pregnancy on male adult offspring cardiac health after feeding a high-fat diet in an established transgenic rat model. Methods We applied our rat model for maternal type 2 diabetes characterised by maternal insulin resistance with hyperglycaemia and hyperinsulinaemia. Diabetes was induced preconceptionally via doxycycline-induced knock down of the insulin receptor in transgenic rats. Male wild-type offspring of diabetic and normoglycaemic pregnancies were raised by foster mothers, followed up into adulthood and subgroups were challenged by a high-fat diet. Cardiac phenotype was assessed by innovative speckle tracking echocardiography, circulating factors, immunohistochemistry and gene expression in the heart. Results When feeding normal chow, we did not observe differences in cardiac function, gene expression and plasma brain natriuretic peptide between adult diabetic or normoglycaemic offspring. Interestingly, when being fed a high-fat diet, adult offspring of diabetic pregnancy demonstrated decreased global longitudinal (−14.82 ± 0.59 vs −16.60 ± 0.48%) and circumferential strain (−23.40 ± 0.57 vs −26.74 ± 0.34%), increased relative wall thickness (0.53 ± 0.06 vs 0.37 ± 0.02), altered cardiac gene expression, enlarged cardiomyocytes (106.60 ± 4.14 vs 87.94 ± 1.67 μm), an accumulation of immune cells in the heart (10.27 ± 0.30 vs 6.48 ± 0.48 per fov) and higher plasma brain natriuretic peptide levels (0.50 ± 0.12 vs 0.12 ± 0.03 ng/ml) compared with normoglycaemic offspring on a high-fat diet. Blood pressure, urinary albumin, blood glucose and body weight were unaltered between groups on a high-fat diet. Conclusions/interpretation Diabetic pregnancy in rats induces cardiac dysfunction, left ventricular hypertrophy and altered proinflammatory status in adult offspring only after a high-fat diet. A diabetic pregnancy itself was not sufficient to impair myocardial function and gene expression in male offspring later in life. This suggests that a postnatal high-fat diet is important for the development of cardiac dysfunction in rat offspring after diabetic pregnancy. Our data provide evidence that a diabetic pregnancy is a novel cardiac risk factor that becomes relevant when other challenges, such as a high-fat diet, are present. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Diabetic pregnancy as a novel risk factor for cardiac dysfunction in the offspring—the heart as a target for fetal programming in rats

et al. 2021

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“…For instance, the telomeric repeat-containing RNAs, known as TERRA, have been positively associated with embryo quality in in vitro fertilization/intracytoplasmatic sperm injection-embryo transfer (IVF/ICSI-ET) treatments [40]. Moreover, pregnancy success rates in the context of ART have been associated with shorter telomere length in newborns [41]. In that study, a number of factors have been investigated, including BMI, smoking status, alcohol and stress.…”

Section: The Role Of Telomeresmentioning

confidence: 99%

Insights into the Role of Telomeres in Human Embryological Parameters. Opinions Regarding IVF

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et al. 2021

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Telomeres promote genome integrity by protecting chromosome ends from the activation of the DNA damage response and protecting chromosomes from the loss of coding sequences due to the end replication problem. Telomere length (TL) is progressively shortened as age progresses, thus resulting in cellular senescence. Therefore, TL is in strong adverse linear correlation with aging. Mounting evidence supports the notion that telomeres and male/female infertility are in a close relationship, posing the biology of telomeres as a hot topic in the era of human-assisted reproduction. Specifically, the length of sperm telomeres is gradually increasing as men get older, while the telomere length of the oocytes seems not to follow similar patterns with that of sperm. Nonetheless, the telomere length of the embryos during the cleavage stages seems to have a paternal origin, but the telomere length can be further extended by telomerase activity during the blastocyst stage. The latter has been proposed as a new molecular biomarker with strong predictive value regarding male infertility. As far as the role of telomeres in assisted reproduction, the data is limited but the length of telomeres in both gametes seems to be affected mainly by the cause of infertility rather than the assisted reproductive therapy (ART) procedure itself. The present review aims to shed more light into the role of telomeres in human embryological parameters, including gametes and embryos and also presents opinions regarding the association between telomeres and in vitro fertilization (IVF).

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“…Genetic and environmental factors regulate telomere length throughout the lifespan of each person, starting from in utero conditions [ 15 – 17 ]. Tracking telomere length from birth to adulthood, it was recently shown that the newborn telomere predicts later life telomere length [ 18 ], pointing to the importance of determining the initial state of newborn telomere and its significance for later life [ 19 ]. Maternal exposures in pregnancy are critical predictors of telomere length in offspring as a long-term trajectory determining the susceptibility of the individual to chronic diseases [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Maternal opioid use is reflected on leukocyte telomere length of male newborns

et al. 2021

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Opioid use accelerates normal aging in adults that raises a question on whether it may trans-generationally affect aging and aging biomarkers in the offspring of users as well? In the present research, we investigated the relative telomere length in umbilical cord blood of newborns born to opioid consuming mothers compared to normal controls. Telomere length shortening is a known biomarker of aging and aging related diseases. Its measure at birth or early in life is considered as a predictor of individual health in adulthood. Here, we performed a case-control study to investigate whether maternal opioid use affects newborns relative telomere length (RTL). 57 mother-newborn dyads were included in this study, 30 neonates with opioid using mothers (OM), and 27 with not-opioid using mothers (NOM)). RTL was measured in leukocyte cells genomic DNA using real-time PCR. The correlation of maternal opioid use with neonates telomer length was assessed using logistic regression analysis. The results displayed a significant association between odds ratio of long RTL and maternal opioid use when sensitivity analysis was performed by neonate sex; where the data indicates significantly increased odds ratio of long leukocyte RTL in association with maternal opioid use in male neonates only. Further work is necessary to assess this association in larger samples and test the potential underlying mechanisms for this observation.

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Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates

Cited by 6 publications

References 47 publications

Diabetic pregnancy as a novel risk factor for cardiac dysfunction in the offspring—the heart as a target for fetal programming in rats

Diabetic pregnancy as a novel risk factor for cardiac dysfunction in the offspring—the heart as a target for fetal programming in rats

Insights into the Role of Telomeres in Human Embryological Parameters. Opinions Regarding IVF

Maternal opioid use is reflected on leukocyte telomere length of male newborns

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