Blastomere removal affects homeostatic control leading to obesity in male mice

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. 61-72
Author(s):  
Magdalena Kotlarska ◽  
Dawid Winiarczyk ◽  
Wiesława Florek ◽  
Marta Ziętek ◽  
Jolanta Pęczkowicz-Szyszka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Homeostasis ◽  
Assisted Reproductive Technologies ◽  
Receptor Gene ◽  
Reproductive Technologies ◽  
Preimplantation Embryos ◽  
Preimplantation Genetic Testing ◽  
Ghrelin Receptor ◽  
Blastomere Biopsy

Preimplantation embryos are particularly vulnerable to environmental perturbations, including those related to assisted reproductive technologies. Invasive embryo manipulations, such as blastomere biopsy, are applied worldwide in clinical settings for preimplantation genetic testing. Mouse models have previously shown that blastomere biopsy may be associated with altered phenotypes in adult offspring. The aim of the present study was to investigate the specific contribution of blastomere removal to the physiological, behavioral, and molecular regulators of energy homeostasis, as compared to sham manipulation (re-introducing the blastomere into the embryo after its removal) and in vitro culture. Mice derived from 8-cell embryos subjected to blastomere removal displayed: (i) higher body weight and adiposity, (ii) increased food intake and sucrose preference, (iii) decreased time of immobility in the tail suspension test, and (iv) resistance to weight loss after social isolation or following 3 days of physical exercise – compared to mice derived from sham biopsy or from in vitro-cultured embryos. Mice generated after blastomere removal also had increased circulating leptin and leptin gene expression in adipose tissue, as well as increased ghrelin receptor gene expression in the hypothalamus, compared to control mice. The effects of blastomere biopsy on offspring phenotype were sexually dimorphic, with females not being affected. These results indicate that blastomere deprivation, rather than other perturbations of the blastomere biopsy procedure, programs male embryos to develop physiological, behavioral, and molecular dysregulation of energy homeostasis, leading to postnatal obesity.

NON-INVASIVE METHODS FOR STUDYING THE POTENTIAL OF HUMAN EMBRYO FOR IMPLANTATION

2021 ◽  
pp. 29-37
Author(s):  
Василий Николаевич Попов ◽  
Роман Борисович Стукалин ◽  
Валерия Александровна Грибанова
Keyword(s):  
Assisted Reproductive Technologies ◽  
Culture Media ◽  
Uterine Cavity ◽  
Married Couples ◽  
Reproductive Technologies ◽  
Preimplantation Embryos ◽  
Preimplantation Genetic Testing ◽  
Vitro Fertilization ◽  
Non Invasive

В статье проводится анализ представленных на сегодня инвазивных и неинвазивных методов исследования преимплантационных эмбрионов. Показана эффективность преимплантационного генетического тестирования эмбрионов до переноса в полость матки. Также рассмотрены альтернативные менее инвазивные варианты изучения жизнеспособности эмбрионов, которые могли бы являться маркерами успешной имплантации. Проблема бесплодного брака с каждым годом становится все более и более значимой. Для части супружеских пар единственной возможностью рождения ребенка становится лечение методами вспомогательных репродуктивных технологий, эффективность которых остается на сегодняшний день не более 50 %. Особенно важным является поиск новых методик, позволяющих повысить результативность процедур экстракорпорального оплодотворения. В этом направлении крайне интересным является изучение неизвазивных методов оценки имплантационного потенциала эмбрионов. В анализе представлены работы по изучению протеома, метаболома и транскриптома эмбриона. Понимание молекулярного состава культуральных сред, в которых происходило развитие эмбриона до пятых суток культивирования, позволит глубже понять физиологию раннего развития, а также установить неивазивные критерии отбора эмбриона с лучшим имплантационным потенциалом и тем самым повысить эффективность проводимых программ вспомогательных репродуктивных технологий The article analyzes the currently presented invasive and non-invasive methods for studying preimplantation embryos. The efficiency of preimplantation genetic testing of embryos before transfer to the uterine cavity has been shown. Also considered are alternative less invasive options for studying the viability of embryos, which could be markers of successful implantation. The problem of sterile marriage is becoming more and more significant every year. For some married couples, the only possibility of having a child is treatment with methods of assisted reproductive technologies, the effectiveness of which remains at most 50% today. It is especially important to search for new techniques to improve the effectiveness of in vitro fertilization procedures. In this direction, it is extremely interesting to study non-invasive methods for assessing the implantation potential of embryos. The analysis presents works on the study of the proteome, metabolome and transcriptome of the embryo. Understanding the molecular composition of the culture media in which the development of the embryo took place until the fifth day of cultivation will allow a deeper understanding of the physiology of early development and also establish non-invasive criteria for the selection of embryos with the best implantation potential and thereby increase the efficiency of the programs of assisted reproductive technologies

Ex vivo early embryo development and effects on gene expression and imprinting

2005 ◽  
Vol 17 (3) ◽  
pp. 361 ◽  
Author(s):  
David K. Gardner ◽  
Michelle Lane
Keyword(s):  
Gene Expression ◽  
Embryo Development ◽  
Assisted Reproductive Technologies ◽  
Ex Vivo ◽  
Reproductive Technologies ◽  
Developmental Competence ◽  
Laboratory Animals ◽  
Cell Physiology ◽  
Mammalian Embryo

The environment to which the mammalian embryo is exposed during the preimplantation period of development has a profound effect on the physiology and viability of the conceptus. It has been demonstrated that conditions that alter gene expression, and in some instances the imprinting status of specific genes, have all previously been shown to adversely affect cell physiology. Thus, questions are raised regarding the aetiology of abnormal gene expression and altered imprinting patterns, and whether problems can be averted by using more physiological culture conditions. It is also of note that the sensitivity of the embryo to its surroundings decreases as development proceeds. Post compaction, environmental conditions have a lesser effect on gene function. This, therefore, has implications regarding the conditions used for IVF and the culture of the cleavage stage embryo. The developmental competence of the oocyte also impacts gene expression in the embryo, and therefore superovulation has been implicated in abnormal methylation and imprinting in the resultant embryo. Furthermore, the genetics and dietary status of the mother have a profound impact on embryo development and gene expression. The significance of specific animal models for human assisted reproductive technologies (ART) is questioned, given that most cattle data have been obtained from in vitro-matured oocytes and that genes imprinted in domestic and laboratory animals are not necessarily imprinted in the human. Patients treated with ART have fertility problems, which in turn may predispose their gametes or embryos to greater sensitivities to the process of ART. Whether this is from the drugs involved in the ovulation induction or from the IVF, intracytoplasmic sperm injection or culture procedures themselves remains to be determined. Alternatively, it may be that epigenetic alterations are associated with infertility and symptoms are subsequently revealed through ART. Whatever the aetiology, continued long-term monitoring of the children conceived through ART is warranted.

scholarly journals Does every family couple that being treated with assisted reproductive technologies need to use preimplantation genetic testing for aneuploidy (PGT-A)?

2019 ◽  
Vol 23 (2) ◽  
pp. 316-320
Author(s):  
O. L. Lyovkina ◽  
S. S. Derii ◽  
Y. R. Kuzmenko
Keyword(s):  
In Vitro Fertilization ◽  
Reproductive Medicine ◽  
Literature Search ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Current Status ◽  
Preimplantation Genetic Testing ◽  
Vitro Fertilization ◽  
Further Development

The increase in the frequency of using assisted reproductive technologies (ART) dictates the need for pre-implantation diagnosis of embryos to determine which of them are euploid and recommended for embryo transfer (ET), since the main cause of implantation failures when using in vitro fertilization (IVF) is ET aneuploid or mosaic ETs or mosaic imitations that use in vitro fertilization (IVF) is ET aneuploid or mosaic imitative failures when using in vitro fertilization (IVF) is ET aneuploid or mosaic imitations. . For this purpose, the PGT-A technology was created, since the appearance of which and its further development there have been discussions about the feasibility of using PGT-A for each pair, which turned to the use of ART. The purpose of this literature review is to describe the current status of PGT-A and determine the prospects for its widespread adoption in the practice of reproductive medicine. A literature search was carried out in the PubMed and Cochrane databases for the last 10 years. An analysis of the literature has shown that IVF with PGT-A technology has significant advantages over traditional IVF; The technology has a number of technical and financial limitations, which makes it difficult to massively introduce technology into the practice of reproductive medicine, therefore at this stage there should be clear indications for using IVF with PGT-A.

scholarly journals Perturbations in imprinted methylation from assisted reproductive technologies but not advanced maternal age in mouse preimplantation embryos

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Audrey J. Kindsfather ◽  
Megan A. Czekalski ◽  
Catherine A. Pressimone ◽  
Margaret P. Erisman ◽  
Mellissa R. W. Mann
Keyword(s):  
Embryo Culture ◽  
Maternal Age ◽  
Assisted Reproductive Technologies ◽  
Advanced Maternal Age ◽  
Reproductive Technologies ◽  
Blastocyst Stage ◽  
Preimplantation Embryos ◽  
Clinical Methods ◽  
First Time

Abstract Background Over the last several decades, the average age of first-time mothers has risen steadily. With increasing maternal age comes a decrease in fertility, which in turn has led to an increase in the use of assisted reproductive technologies by these women. Assisted reproductive technologies (ARTs), including superovulation and embryo culture, have been shown separately to alter imprinted DNA methylation maintenance in blastocysts. However, there has been little investigation on the effects of advanced maternal age, with or without ARTs, on genomic imprinting. We hypothesized that ARTs and advanced maternal age, separately and together, alter imprinted methylation in mouse preimplantation embryos. For this study, we examined imprinted methylation at three genes, Snrpn, Kcnq1ot1, and H19, which in humans are linked to ART-associated methylation errors that lead to imprinting disorders. Results Our data showed that imprinted methylation acquisition in oocytes was unaffected by increasing maternal age. Furthermore, imprinted methylation was normally acquired when advanced maternal age was combined with superovulation. Analysis of blastocyst-stage embryos revealed that imprinted methylation maintenance was also not affected by increasing maternal age. In a comparison of ARTs, we observed that the frequency of blastocysts with imprinted methylation loss was similar between the superovulation only and the embryo culture only groups, while the combination of superovulation and embryo culture resulted in a higher frequency of mouse blastocysts with maternal imprinted methylation perturbations than superovulation alone. Finally, the combination of increasing maternal age with ARTs had no additional effect on the frequency of imprinted methylation errors. Conclusion Collectively, increasing maternal age with or without superovulation had no effect of imprinted methylation acquisition at Snrpn, Kcnq1ot1, and H19 in oocytes. Furthermore, during preimplantation development, while ARTs generated perturbations in imprinted methylation maintenance in blastocysts, advanced maternal age did not increase the burden of imprinted methylation errors at Snrpn, Kcnq1ot1, and H19 when combined with ARTs. These results provide cautious optimism that advanced maternal age is not a contributing factor to imprinted methylation errors in embryos produced in the clinic. Furthermore, our data on the effects of ARTs strengthen the need to advance clinical methods to reduce imprinted methylation errors in in vitro-produced embryos.

scholarly journals Research Resource: Small RNA-seq of Human Granulosa Cells Reveals miRNAs in FSHR and Aromatase Genes

2013 ◽  
Vol 27 (7) ◽  
pp. 1128-1141 ◽  
Author(s):  
Agne Velthut-Meikas ◽  
Jaak Simm ◽  
Timo Tuuri ◽  
Juha S. Tapanainen ◽  
Madis Metsis ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Vitro Fertilization ◽  
Granulosa Cells ◽  
Assisted Reproductive Technologies ◽  
Regulation Of Gene Expression ◽  
Reproductive Technologies ◽  
Vitro Fertilization ◽  
Human Granulosa Cells ◽  
Expression Studies

Abstract The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signaling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and in vitro fertilization success. However, the posttranscriptional gene expression studies on micro-RNA (miRNA) level in the human ovary have been scarce. The current study determined the miRNA profile by deep sequencing of the 2 intrafollicular somatic cell types: mural and cumulus granulosa cells (MGCs and CGCs, respectively) isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Altogether, 936 annotated and 9 novel miRNAs were identified. Ninety of the annotated miRNAs were differentially expressed between MGCs and CGCs. Bioinformatic prediction revealed that TGFβ, ErbB signaling, and heparan sulfate biosynthesis were targeted by miRNAs in both granulosa cell populations, whereas extracellular matrix remodeling, Wnt, and neurotrophin signaling pathways were enriched among miRNA targets in MGCs. Two of the nine novel miRNAs found were of intronic origin: one from the aromatase and the other from the FSH receptor gene. The latter miRNA was predicted to target the activin signaling pathway. In addition to revealing the genome-wide miRNA signature in human granulosa cells, our results suggest that posttranscriptional regulation of gene expression by miRNAs could play an important role in the modification of gonadotropin signaling. miRNA expression studies could therefore lead to new prognostic markers in assisted reproductive technologies.

Impact of equine assisted reproductive technologies (standard embryo transfer or intracytoplasmic sperm injection (ICSI) with in vitro culture and embryo transfer) on placenta and foal morphometry and placental gene expression

2018 ◽  
Vol 30 (2) ◽  
pp. 371 ◽  
Author(s):  
Orlando A. Valenzuela ◽  
Anne Couturier-Tarrade ◽  
Young-Ho Choi ◽  
Marie-Christine Aubrière ◽  
Justin Ritthaler ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Vitro Culture ◽  
Embryo Transfer ◽  
Intracytoplasmic Sperm Injection ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Placental Development ◽  
Quarter Horse ◽  
Equine Assisted

Assisted reproductive technologies (ARTs) such as intracytoplasmic sperm injection (ICSI), in vitro embryo culture and embryo transfer (ET) may be associated with alterations in fetal and placental development. In horses, ET has been used for decades. More recently, in vitro embryo production by ICSI and in vitro culture, followed by embryo transfer (ICSI-C) has become an accepted method for clinical foal production. However, no information is available on the effects of ICSI-C or even of standard ET itself on placental and neonatal parameters in horses. We therefore evaluated placental and neonatal morphology and placental gene expression in reining- and cutting-type American Quarter Horse foals produced using different technologies. Thirty foals and placentas (naturally conceived (NC), ET and ICSI-C; 10 in each group) were examined morphometrically. The only parameter that differed significantly between groups was the length of the foal upper hindlimb, which was longer in ET and ICSI-C than in NC foals. Evaluation of placental mRNA expression for 17 genes related to growth and vascularisation showed no difference in gene expression between groups. These data indicate that within this population, use of ARTs was not associated with meaningful changes in foal or placental morphometry or in expression of the placental genes evaluated.

Thickness of endometrium: predictor of the effectiveness of IVF/ICSI programs (literature review)

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (1) ◽  
pp. 113-116
Author(s):  
L A Bagdasaryan ◽  
I E Korneyeva
Keyword(s):  
Assisted Reproductive Technologies ◽  
Endometrial Thickness ◽  
Molecular Genetic ◽  
Uterine Cavity ◽  
Reproductive Technologies ◽  
Genetic Characteristics ◽  
Vitro Fertilization ◽  
Need To Evaluate ◽  
The Relationship

The aim of the study is to systematically analyze the data available in the modern literature on the relationship between endometrial thickness and the frequency of pregnancy in the program of assisted reproductive technologies (ART). Materials and methods. The review includes data from foreign and domestic articles found in PubMed on this topic. Results. The article presents data on the relationship between the thickness of the endometrium and the frequency of pregnancy in ART programs. The greatest number of studies is devoted to the evaluation of the relationship between the thickness of the endometrium and the frequency of pregnancy on the day of the ovulation trigger. Data are presented on the existence of a correlation between the thickness of the endometrium measured on the day of the ovulation trigger and the frequency of clinical pregnancy, as well as data on the need to evaluate the structure of the endometrium and the state of subendometric blood flow. The importance of multilayered (three-layered) endometrium as a prognostic marker of success in in vitro fertilization/intracytoplasmic sperm injection programs in the ovum is emphasized. The conclusion. The thickness of the endometrium can not be used as an argument for canceling the cycle or abolishing embryo transfer to the uterine cavity. Further studies in this direction are needed with a study of the morphological and molecular genetic characteristics of the endometrium, which in the future will allow us to evaluate the relationship between the thickness of the endometrium and the probability of pregnancy.

Legal restrictions on pre-implantation genetic diagnostics in the framework of in vitro fertilization procedure: foreign experience and Russian perspective

2019 ◽  
Author(s):  
N.A. Altinnik , S.S. Zenin , V.V. Komarova et all
Keyword(s):  
In Vitro Fertilization ◽  
Assisted Reproductive Technologies ◽  
Genetic Diseases ◽  
Genetic Diagnosis ◽  
Reproductive Technologies ◽  
Legal Regulation ◽  
Genetic Diagnostics ◽  
Vitro Fertilization ◽  
Medical Indications

The article discusses the factors that determine the content of the legal limitations of pre-implantation genetic diagnosis in the framework of the in vitro fertilization procedure, taking into account international experience and modern domestic regulatory legal regulation of the field of assisted reproductive technologies. The authors substantiates the conclusion that it is necessary to legislate a list of medical indications for preimplantation genetic diagnosis, as well as the categories of hereditary or other genetic diseases diagnosed in the framework of this procedure.

scholarly journals Prevalence of pathogenic copy number variants among children conceived by donor oocyte

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sandra Monfort ◽  
Carmen Orellana ◽  
Silvestre Oltra ◽  
Mónica Rosello ◽  
Alfonso Caro-Llopis ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Copy Number ◽  
Assisted Reproductive Technologies ◽  
Copy Number Variants ◽  
Reproductive Technologies ◽  
Significant Excess ◽  
Vitro Fertilization ◽  
Donor Oocyte ◽  
Increased Risk

AbstractDevelopment of assisted reproductive technologies to address infertility has favored the birth of many children in the last years. The majority of children born with these treatments are healthy, but some concerns remain on the safety of these medical procedures. We have retrospectively analyzed both the fertilization method and the microarray results in all those children born between 2010 and 2019 with multiple congenital anomalies, developmental delay and/or autistic spectrum disorder (n = 486) referred for array study in our center. This analysis showed a significant excess of pathogenic copy number variants among those patients conceived after in vitro fertilization with donor oocyte with respect to those patients conceived by natural fertilization (p = 0.0001). On the other hand, no significant excess of pathogenic copy number variants was observed among patients born by autologous oocyte in vitro fertilization. Further studies are necessary to confirm these results and in order to identify the factors that may contribute to an increased risk of genomic rearrangements, as well as consider the screening for genomic alterations after oocyte donation in prenatal diagnosis.

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