Modern aspects of biological modeling of sexual development disorders

Author(s):  
Ю.Ю. Чеботарева ◽  
В.Г. Овсянников ◽  
М.А. Родина ◽  
И.В. Подгорный ◽  
М.Я. Хутиева

Введение. Изучение механизмов развития репродуктивных нарушений в условиях эксперимента на крысах является одним из важных направлений современной патофизиологии. Крыса имеет функционирующий эстральный цикл, трехнедельную гестацию и гемохориальный тип плацентации. На циклических изменениях в яичниках и эпителии влагалища крысы базируется биологическое моделирование эндокринной гинекологической патологии. В настоящее время интерес представляет разработка экспериментальной модели нарушения полового созревания в периоде детства. Нарушение полового созревания может приводить к различным патологическим изменениям в сфере репродуктивного здоровья в будущем, актуальность данной проблемы очевидна. Цель работы - изучение современных аспектов моделирования преждевременного полового созревания у девочек. Методика. Анализ современных отечественных и зарубежных работ, касающихся механизмов преждевременного полового созревания и исследований в области моделирования данной патологии в экспериментах на крысах. Результаты. Преждевременное половое созревание у девочек - нарушение, проявляющееся развитием одного или комплекса признаков половой зрелости до 7 летнего возраста. Детерминация полового развития связана с особенностью генетических и эпигенетических факторов. К последним традиционно относят характер питания, стресс как адаптационную реакцию, интегрированную с активацией гормонопоэза. Фактор питания связан с функционированием гормонов жировой ткани, включая лептин, грелин, эффектами инсулиноподобного фактора роста. В ряде экспериментальных исследований, связанных с воздействием факторов питания, стресса и световой дезадаптации на репродуктивную систему животного, доказано значимое влияние последней на нейромедиаторные системы мозга. Наименее изученными в механизме преждевременного полового созревания остаются вопросы нейроэндокринной регуляции гонадной оси системой KISS/KISS1R. Продолжение изучения ассоциации изменения профиля нейромедиаторов моноаминового ряда и динамики кисспептина в эксперименте на крысах способно расширить представление о механизмах половой дифференцировки мозга и транслировать полученные данные в клиническую практику, связанную с обследованием девочек с преждевременным половым созреванием. Заключение. В связи с малой распространенностью и ограниченностью представлений о патогенезе преждевременного полового созревания, данная проблема требует детального изучения. Необходимо дальнейшее изучение патогенетических основ данной патологии в условиях биологического моделирования на самках крыс раннего возраста. Introduction. Studying pathogenetic mechanisms responsible for development of reproductive disorders in rat models is an important direction of modern pathophysiology. The rat has a functioning estrous cycle, a three-week gestation, and a hemochorial placentation. Biological modeling of endocrine gynecological pathology is based on cyclic changes in the ovaries and in the epithelium of the rat vagina. Currently, the development of an experimental model of puberty disorders in childhood is of interest. Premature puberty can lead to various pathological changes in future reproductive health. The relevance of this problem is obvious. The aim of this work was to study modern aspects of modeling premature puberty in girls. Method. Modern domestic and foreign reviews on the mechanism of premature puberty and studies of modeling this pathology in experiments on rats were analyzed. Results. Premature puberty in girls is a disorder manifested by the development of one or all signs of puberty as early as before the age of 7 yrs. Sexual development is associated with characteristic roles of genetic and epigenetic factors. The latter traditionally include nutrition and stress as an adaptive reaction integrated with the activation of hormone synthesis. The nutrition factor is related with the functioning of adipose tissue hormones, including leptin, ghrelin, and the effects of insulin-like growth factor. A number of experimental studies on rats addressing effects of nutrition, stress, and light maladaptation on the reproductive system have demonstrated its significant effect on brain neurotransmitter systems. Regarding the mechanism of premature puberty, the least studied issue is the neuroendocrine regulation of the gonadal axis by the KISS/KISS1R system. Continuing study of the association between changes in the profile of monoamine neurotransmitters and the dynamics of kisspeptin in experiments on rats can expand understanding of sexual differentiation mechanisms in the brain. The obtained data can be translated into clinical practice for the management of premature puberty in girls. Conclusion. Due to the rare prevalence of premature puberty and insufficient data on its pathogenesis, this problem requires detailed study. It is necessary to further study the mechanism of this pathology by biological modeling on female rats at an early age.

2017 ◽  
Vol 23 (1) ◽  
Author(s):  
C.A. JAWALE

Ovarian maturation by neurosecretory cells in the brain of freshwater crab, Barytelphusa cunicularis have been examined. The histological scrutiny of the brain of Barytelphusa cunicularis related with three types (A, B and C) of neurosecretory cells, which are classified on the basis of size, shape and tinctorial characters. All these types of cells marked annual cyclic changes of cytoplasmic material in association with ovarian cycle. The activity of these cells has been correlated with the ovarian cycle. They are distinguishable by their size, nature locations, shape, nucleus position, cell measure and the secretory product in the cytoplasm. The result indicates that the neurosecretory A, B and C cells of the brain seen involved in the process of mating ovulation. The neurosecretory materials staining intensity index of these cells is described.


1979 ◽  
Vol 90 (3) ◽  
pp. 385-393 ◽  
Author(s):  
José Borrell ◽  
Flavio Piva ◽  
Luciano Martini

ABSTRACT Drugs able to mimic or to antagonize the action of catecholamines have been implanted bilaterally into the basomedial region of the amygdala of adult castrated female rats. The animals were killed at different intervals after the implantation of the different drugs, and serum levels of LH and FSH were measured by radioimmunoassay. The results have shown that the intra-amygdalar implantation of the alpha-adrenergic blocker phenoxybenzamine induces a significant increase of the release both of LH and FSH. The implantation of the beta-adrenergic blocker propranolol brings about a rise of LH only. The dopamine receptor blocker pimozide stimulates the release of LH and exerts a biphasic effect (stimulation followed by inhibition) of FSH secretion. The alpha-receptor stimulant clonidine and the dopaminergic drug 2-Br-alpha-ergocryptine were without significant effects. From these observations it is suggested that the adrenergic signals reaching the basomedial area of the amygdala (possibly from the brain stem) may be involved in the modulation of gonadotrophin secretion.


2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.


PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0210406 ◽  
Author(s):  
Laura Arroyo ◽  
Daniel Valent ◽  
Ricard Carreras ◽  
Raquel Peña ◽  
Josefa Sabrià ◽  
...  

2006 ◽  
Vol 291 (1) ◽  
pp. R155-R162 ◽  
Author(s):  
Stephanie A. Dean ◽  
Junhui Tan ◽  
Roselyn White ◽  
Edward R. O’Brien ◽  
Frans H. H. Leenen

The present study tested the hypothesis that 17β-estradiol (E2) inhibits increases in angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT1R) in the brain and heart after myocardial infarction (MI) and, thereby, inhibits development of left ventricular (LV) dysfunction after MI. Age-matched female Wistar rats were treated as follows: 1) no surgery (ovary intact), 2) ovariectomy + subcutaneous vehicle treatment (OVX + Veh), or 3) OVX + subcutaneous administration of a high dose of E2 (OVX + high-E2). After 2 wk, rats were randomly assigned to coronary artery ligation (MI) and sham operation groups and studied after 3 wk. E2 status did not affect LV function in sham rats. At 2–3 wk after MI, impairment of LV function was similar across MI groups, as measured by echocardiography and direct LV catheterization. LV ACE mRNA abundance and activity were increased severalfold in all MI groups compared with respective sham animals and to similar levels across MI groups. In most brain nuclei, ACE and AT1R densities increased after MI. Unexpectedly, compared with the respective sham groups the relative increase was clearest (20–40%) in OVX + high-E2 MI rats, somewhat less (10–15%) in ovary-intact MI rats, and least (<10–15%) in OVX + Veh MI rats. However, because in the sham group brain ACE and AT1R densities increased in the OVX + Veh rats and decreased in the OVX + high-E2 rats compared with the ovary-intact rats, actual ACE and AT1R densities in most brain nuclei were modestly higher (<20%) in OVX + Veh MI rats than in the other two MI groups. Thus E2 does not inhibit upregulation of ACE in the LV after MI and amplifies the percent increases in ACE and AT1R densities in brain nuclei after MI, despite E2-induced downregulation in sham rats. Consistent with these minor variations in the tissue renin-angiotensin system, during the initial post-MI phase, E2 appears not to enhance or hinder the development of LV dysfunction.


1999 ◽  
Vol 80 (2) ◽  
pp. 94-96
Author(s):  
V. I. Danilov

The results of experimental studies made it possible to draw a conclusion on the reality of cerebral vessels reactivity recovery using drugs with primary neurometabolic activity, in particular, dimephosphone, sermion and pyracetam. The advantages of low-toxic nonauticholinesterasic organic phosphorus compounds among the correctors of regulatory mechanisms of circular provision of the brain are shown.


2009 ◽  
Vol 55 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Kazuyo TUJIOKA ◽  
Miho OHSUMI ◽  
Kenji HORIE ◽  
Mujo KIM ◽  
Kazutoshi HAYASE ◽  
...  

2001 ◽  
Vol 1 ◽  
pp. 681-683 ◽  
Author(s):  
Catherine A. Harris

The potential for man-made chemicals to mimic or antagonise natural hormones is a controversial issue, but one for which increasing amounts of evidence are being gathered worldwide. The controversy surrounds not so much the matter of whether these chemicals can mimic hormones invitro— this phenomenon has been widely accepted in the scientific world — but more whether, as a result, they can disrupt reproduction in a wildlife situation. It has, nevertheless, been acknowledged that many wildlife populations are exhibiting reproductive and/or developmental abnormalities such as intersex gonads in wild roach populations in the U.K.[1] and various reproductive disorders in alligators in Lake Apopka, Florida[2]. However, the causative agents for many of these effects are difficult to specify, due to the extensive mixtures of chemicals — each of which may act via different pathways — to which wild populations are exposed, together with the wide variability observed even in natural (uncontaminated) habitats. As a result, any information detailing fundamental mechanism of action of the so-called endocrine disrupting chemicals (EDCs) is of use in determining whether or not these chemicals, as they are present in the environment, may in fact be capable of causing some of the effects observed in wildlife over recent years.


Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1361
Author(s):  
Agnieszka M. Jurga ◽  
Martyna Paleczna ◽  
Justyna Kadluczka ◽  
Katarzyna Z. Kuter

The idea of central nervous system as one-man band favoring neurons is long gone. Now we all are aware that neurons and neuroglia are team players and constant communication between those various cell types is essential to maintain functional efficiency and a quick response to danger. Here, we summarize and discuss known and new markers of astroglial multiple functions, their natural heterogeneity, cellular interactions, aging and disease-induced dysfunctions. This review is focused on newly reported facts regarding astrocytes, which are beyond the old stereotypes. We present an up-to-date list of marker proteins used to identify a broad spectrum of astroglial phenotypes related to the various physiological and pathological nervous system conditions. The aim of this review is to help choose markers that are well-tailored for specific needs of further experimental studies, precisely recognizing differential glial phenotypes, or for diagnostic purposes. We hope it will help to categorize the functional and structural diversity of the astroglial population and ease a clear readout of future experimental results.


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