ONTOGENETIC PRINCIPLES OF ACCELERATED AGING AND THE PROSPECTS FOR ITS PREVENTION AND TREATMENT

В статье рассмотрен феномен «внутриутробного программирования», в значительной степени определяющий дальнейший жизненный цикл и вероятность развития ряда возраст-ассоциированных патологических процессов. С позиций современной науки при использовании большого литературного материала обсуждается возможность формирования патологического (ускоренного) старения на самых разных этапах онтогенеза. В тесной взаимосвязи обсуждаются причины, механизмы и фенотипические проявления ускоренного старения и возможности ранней, начиная с перинатального периода, диагностики и прогнозирования возраст-ассоциированных патологий. This article examines the phenomenon of «intrauterine programming», which largely determines the further life cycle and the likelihood of developing a number of age-associated pathological processes. The possibility of the formation of pathological (accelerated) aging at various stages of ontogenesis is discussed with the use of large literary material from the standpoint of modern science. The reasons, mechanisms and phenotypic manifestations of accelerated aging and the possibilities of the earliest one, its diagnosis starting from the perinatal period, and prediction of age-associated pathologies are discussed in close interrelation.

Gender difference in adrenal developmental toxicity induced by dexamethasone and its intrauterine programming mechanism

Background and Purpose: Dexamethasone is widely used in preterm labor and related diseases. However, prenatal dexamethasone exposure (PDE) can cause multi-organ developmental toxicities in offspring. Our previous study found the occurrence of fetal-originated diseases were associated with adrenal developmental programming alteration in offspring. Here, we investigated the effects of PDE on the adrenal function in offspring and its intrauterine programming mechanism. Experimental Approach: A rat model of PDE was established to observe the alteration of adrenal steroidogenesis in offspring. Further, we confirmed the gender difference of adrenal steroidogenesis and its molecular mechanism combined with in vivo and in vitro experiment. Key Results: PDE caused a decrease in adrenal steroidogenic function in fetal rats, but decreased in males and increased in females after birth. Meanwhile, the adrenal H3K14ac level and expression of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) in PDE offspring were decreased in males and increased in females, suggesting 11β-HSD2 might mediate gender difference of adrenal function. We further confirmed dexamethasone inhibited the H3K14ac level and expression of 11β-HSD2 through GR/SP1/p300 pathway. After bilateral testectomy or ovariectomy in adult PDE offspring rats, adrenal 11β-HSD2 expression and steroidogenic function were both reduced. Using rat primary fetal adrenal cells, the differential expression in AR and ERβ were proved to involve in regulating the gender difference of 11β-HSD2 expression. Conclusion and Implications: This study demonstrated the gender difference in adrenal steroidogenic function of PDE offspring after birth, and elucidates a sex hormone receptor-dependent epigenetically regulating mechanism for adrenal 11β-HSD2 programming alteration.

Folikel Pre-Ovulatori Sapi PO Dara yang Distimulasi Menggunakan PMSG Dosis Rendah

Penelitian ini bertujuan untuk mengetahui perkembangan folikel sapi PO dara yang distimulasi menggunakan PMSG dosis rendah (dosis non-superovulasi) dan perolehan folikel dominan pre-ovulatori sebagai informasi dasar untuk penerapan intrauterine programming pada sapi. Sapi PO dara berjumlah sembilan ekor dibagi ke dalam tiga kelompok dosis PMSG yaitu kontrol (NaCl 0.9% sebagai placebo), dosis PMSG 0.5, dan 1.0 IU/kg BB. Injeksi PMSG dilakukan pada awal gelombang folikel ke-2 berdasarkan perubahan dinamika ovari yang dikonfirmasi menggunakan USG diikuti injeksi PGF2α 48 jam kemudian. Perkembangan folikel sejak injeksi PMSG hingga terbentuknya pre-ovulatori folikel (POF) diamati dan dipetakan menggunakan USG. Jumlah POF tertinggi terdapat pada dosis PMSG 1.0 IU/kg BB (4.67+1.67) secara signifikan (P<0.05), sedangkan POF yang terbentuk pada dosis PMSG 0.5 IU/kg BB berjumlah satu, sama dengan kelompok kontrol (P>0.05). Meskipun jumlah POF yang terbentuk berjumlah satu, namun rataan diameter dan volume kelompok sapi dosis 0.5 IU/kg BB lebih besar 16.13% dan 57.14% secara berurutan dibandingkan kelompok kontrol, diikuti oleh dosis 1.0 IU/kg BB dengan nilai tertinggi secara signifikan (P<0.05). Berdasarkan hasil tersebut dapat diketahui bahwa PMSG 0.5 IU/kg BB dapat terkontrol sehingga dapat digunakan sebagai metode pendekatan intrautering programming pada hewan monotokus.

FEATURES OF REPRODUCTIVE HEALTH OF WOMEN WITH LOW BIRTH WEIGHT AND OVERWEIGHT AT BIRTH

The aim of the study was to clarify obstetric and perinatal risk in women born with low or overweight. Materials and methods. 343 women with birth weight abnormalities were examined. From them 3 groups are made, according to criterion “weight of the woman at a birth”: I – 107 women with low weight at a birth, II – 126 with excess, III – 110 people with normal weight. The anamnesis, in particular, family and own perinatal, as well as nutritional support, anthropometric data, the structure of pregnancy complications, the rate of growth and development of the fetus, perinatal results were determined. Levels of eicosapentaenoic and docosahexaenoic acids were determined as markers of nutritional support of the organism, as indicators of angiogenesis were determined – concentration of vascular endothelial growth factor and placental growth factor in blood, morpho-functional studies of placenta were performed. Results. Women born underweight are more likely to have menstrual disorders (every 4), infertility (every 10), miscarriage (every 5) and gynecological diseases. The pathology of gestation in such women and their mothers is similar in spectrum, which is an example of intrauterine programming. The implementation of this program is facilitated by negative factors of nutritional provision: inadequate breastfeeding, economical type of nutrition in favor of restricting protein foods and deviations in the process of angiogenesis. Conclusions. The importance of perinatal history as a factor that determines the increased risk of menstrual disorders, the frequency of infertility, the pathological course of gestation during pregnancy, the predisposition to placental insufficiency and the birth of a child with low weight. Women born with low birth weight and overweight are a contingent of increased perinatal risk, which is associated with a complicated own perinatal history on the background of obstetric pathology in their mothers. This fact complements the concept of intrauterine programming.

Actual issues of intrauterine programming of health and reproductive function in women with small and large for gestational age birth weight (Сlinical lecture)

The replenishment and updatе of information for practitioners, both primary and specialized care providers, about the impact of a woman’s perinatal history on her future health, formation pathological conditions and diseases, is necessary for the integration of modern physicians into space of individualized (personalized, precision) medicine. In recent years, on the background of a decrease in the birth rate and a negative demographic balance of Ukrainian population, the frequency of birth of newborns with deviations of physical development parameters from the boundaries of population standards has been increasing, and this is projects on reducing of children’s and adolescents’s quality of health, increasing the overall morbidity in adulthood, and reproductive function disorders, in particular, gynecological pathology, infertility, pregnancy complications. In such conditions, the importance of pregravid background for the realization of woman’s reproductive function with a positive result is updated. The article provides up-to-date data that will help to understand the relationship between a woman’s perinatal development and the state of her reproductive system in postnatal ontogenesis, which will maximize individualization of medical observation based on the predicted risk due to the realities of intrauterine programming. Key words: intrauterine programming, reproductive function, low birth weight, overweight at birth, gynecological pathology, pregnancy complications, perinatal risk.