scholarly journals Variants in Maternal Effect Genes and Relaxed Imprinting Control in a Special Placental Mesenchymal Dysplasia Case with Mild Trophoblast Hyperplasia

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 544
Author(s):  
Tien-Chi Huang ◽  
Kung-Chao Chang ◽  
Jen-Yun Chang ◽  
Yi-Shan Tsai ◽  
Yao-Jong Yang ◽  
...  
Keyword(s):  
Maternal Effect ◽  
Hydatidiform Mole ◽  
Placental Tissue ◽  
Differentially Methylated Region ◽  
Normal Birth ◽  
Maternal Effect Genes ◽  
Common Etiology ◽  
Artificial Abortion ◽  
Secondary Dmr ◽  
Placental Mesenchymal Dysplasia

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

scholarly journals A transgenic system for targeted ablation of reproductive and maternal-effect genes

Development ◽  
2021 ◽  
Vol 148 (12) ◽  
Author(s):  
Sylvain Bertho ◽  
Odelya Kaufman ◽  
KathyAnn Lee ◽  
Adrian Santos-Ledo ◽  
Daniel Dellal ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Maternal Effect ◽  
Early Embryo ◽  
Gene Products ◽  
Reverse Genetic ◽  
Genetic Screens ◽  
Maternal Effect Genes ◽  
Forward Genetic Screens ◽  
Embryonic Life ◽  
Bucky Ball

ABSTRACT Maternally provided gene products regulate the earliest events of embryonic life, including formation of the oocyte that will develop into an egg, and eventually into an embryo. Forward genetic screens have provided invaluable insights into the molecular regulation of embryonic development, including the essential contributions of some genes whose products must be provided to the transcriptionally silent early embryo for normal embryogenesis, called maternal-effect genes. However, other maternal-effect genes are not accessible due to their essential zygotic functions during embryonic development. Identifying these regulators is essential to fill the large gaps in our understanding of the mechanisms and molecular pathways contributing to fertility and to maternally regulated developmental processes. To identify these maternal factors, it is necessary to bypass the earlier requirement for these genes so that their potential later functions can be investigated. Here, we report reverse genetic systems to identify genes with essential roles in zebrafish reproductive and maternal-effect processes. As proof of principle and to assess the efficiency and robustness of mutagenesis, we used these transgenic systems to disrupt two genes with known maternal-effect functions: kif5ba and bucky ball.

scholarly journals Identification of maternal-effect genes in zebrafish using maternal crispants

Development ◽  
2021 ◽  
Author(s):  
Cara E. Moravec ◽  
Gabriella C. Voit ◽  
Jarred Otterlee ◽  
Francisco Pelegri
Keyword(s):  
Maternal Effect ◽  
Reverse Genetics ◽  
Germ Line ◽  
Maternal Factors ◽  
Single Generation ◽  
Maternal Effect Genes ◽  
Biallelic Mutations ◽  
Genome Activation

In animals, early development is dependent on a pool of maternal factors, both RNA and proteins, which are required for basic cellular process and cell differentiation until zygotic genome activation. The role of a majority of these maternally expressed factors is not fully understood. By exploiting the biallelic editing ability of CRISPR-Cas9, we identify and characterize maternal-effect genes in a single generation, using a maternal crispant technique. We validated the ability to generate biallelic mutations in the germline by creating maternal crispants that phenocopied previously characterized maternal-effect genes: motley/birc5b, tmi/prc1l, and aura/mid1ip1. Additionally, by targeting maternally expressed genes of unknown function in zebrafish, we identified two new maternal-effect zebrafish genes, kpna7 and fhdc3. The genetic identity of these maternal crispants was confirmed by sequencing haploid progeny from F0 females, which allowed the analysis of newly induced lesions in the maternal germ line. Our studies show that maternal crispants allow for the effective identification and primary characterization of maternal-effect genes in a single generation, facilitating the reverse genetics analysis of maternal factors that drive embryonic development.

scholarly journals A Transgenic System for Targeted Ablation of Reproductive and Maternal-Effect genes

2020 ◽  
Author(s):  
Sylvain Bertho ◽  
Odelya Kaufman ◽  
KathyAnn Lee ◽  
Adrian Santos-Ledo ◽  
Daniel Dellal ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Maternal Effect ◽  
Early Embryo ◽  
Reverse Genetic ◽  
Genetic Screens ◽  
Maternal Effect Genes ◽  
Genetic Systems ◽  
Forward Genetic Screens ◽  
Embryonic Life ◽  
Summary Statement

AbstractMaternally provided gene products regulate the earliest events of embryonic life, including formation of the oocyte that will develop into an egg, and eventually an embryo. Forward genetic screens have provided invaluable insights into the molecular regulation of embryonic development, including essential contributions of some genes whose products must be provided to the transcriptionally silent early embryo for normal embryogenesis, maternal-effect genes. However, other maternal-effect genes are not accessible due to their essential zygotic functions during embryonic development. Identifying these regulators is essential to fill the large gaps in our understanding of the mechanisms and molecular pathways contributing to fertility and maternally regulated developmental processes. To identify these maternal factors, it is necessary to bypass the earlier requirement for these genes so that their potential later functions can be investigated. Here we report reverse genetic systems to identify genes with essential roles in reproductive and maternal-effect processes, as proof of principal and to assess the efficiency and robustness of mutagenesis we used these transgenic systems to disrupt two genes with known maternal-effect functions, kif5Ba and bucky ball.Summary StatementWe report reverse genetic systems to identify essential regulators of reproductive and maternal-effect processes, as proof of principal we used these transgenic systems to disrupt genes with known maternal-effect functions.

scholarly journals Early diagnosis and treatment of hydatidiform mole in adolescent pregnant woman

2021 ◽  
Vol 9 (6) ◽  
pp. 1760
Author(s):  
Putu Harrista Indra Pramana ◽  
Kaspan Kaspan
Keyword(s):  
Ultrasound Imaging ◽  
Complete Blood Count ◽  
Hydatidiform Mole ◽  
Good Condition ◽  
Stable State ◽  
Placental Tissue ◽  
Tissue Formation ◽  
Clinical Appearance ◽  
Elementary School Education ◽  
Normochromic Anemia

Hydatidiform mole belongs to the spectrum of gestational trophoblastic disorders in which abnormal conception leads to excess placental tissue formation in the absence of fetal development. The incidence of hydatidiform mole is quite rare so that not all experienced clinicians handle this case in clinical experience. Therefore, we present a case of hydatidiform mole in an adolescent patient. A 14-year-old primigravida woman, unemployed, with elementary school education, with a gestational age of 16 weeks went to the ER with complaints of vaginal bleeding for 2 days. Physical examination found the fundal height at umbilicus, abdominal tenderness, accompanied by vaginal bloody discharge. Complete blood count found mild normochromic anemia with increased levels of T3 and decreased TSH. Ultrasound imaging found a typical vesicular pattern of a hydatidiform mole. Treatment of molar evacuation by curettage and drainage was carried out one day after presentation and obtained 600 grams of molar tissue. The patient underwent 24 hours of post-operative observation before being discharged in a stable state. The patient presented with a typical clinical appearance of hydatidiform mole. Ultrasound imaging reveals a typical complete hydatidiform mole accompanied by anemia and hyperthyroxinemic which may accompany hydatidiform mole. Evacuation was carried out according to clinical guidelines and the patient was discharged in a good condition.

scholarly journals Maternal-Zygotic Gene Conflict Over Sex Determination: Effects of Inbreeding

Genetics ◽  
2000 ◽  
Vol 155 (3) ◽  
pp. 1469-1479
Author(s):  
John H Werren ◽  
Melanie J Hatcher
Keyword(s):  
Sex Determination ◽  
Maternal Effect ◽  
Genetic Studies ◽  
Genetic Conflict ◽  
Maternal Genotype ◽  
Wide Range ◽  
Maternal Effect Genes ◽  
Invasion Criteria ◽  
Subdivided Populations ◽  
Zygotic Gene

Abstract There is growing evidence that sex determination in a wide range of organisms is determined by interactions between maternal-effect genes and zygotically expressing genes. Maternal-effect genes typically produce products (e.g., mRNA or proteins) that are placed into the egg during oogenesis and therefore depend upon maternal genotype. Here it is shown that maternal-effect and zygotic genes are subject to conflicting selective pressures over sex determination in species with partial inbreeding or subdivided populations. The optimal sex ratios for maternal-effect genes and zygotically expressing genes are derived for two models: partial inbreeding (sibmating) and subdivided populations with local mating in temporary demes (local mate competition). In both cases, maternal-effect genes are selected to bias sex determination more toward females than are zygotically expressed genes. By investigating the invasion criteria for zygotic genes in a population producing the maternal optimum (and vice versa), it is shown that genetic conflict occurs between these genes. Even relatively low levels of inbreeding or subdivision can result in maternalzygotic gene conflict over sex determination. The generality of maternal-zygotic gene conflict to sex determination evolution is discussed; such conflict should be considered in genetic studies of sex-determining mechanisms.

Activation of the easter zymogen is regulated by five other genes to define dorsal-ventral polarity in the Drosophila embryo

Development ◽  
1992 ◽  
Vol 115 (2) ◽  
pp. 607-616 ◽  
Author(s):  
R. Chasan ◽  
Y. Jin ◽  
K.V. Anderson
Keyword(s):  
Maternal Effect ◽  
Serine Proteases ◽  
Drosophila Embryo ◽  
Vitelline Membrane ◽  
Mutant Form ◽  
Wild Type ◽  
Zymogen Activation ◽  
Embryonic Polarity ◽  
Dominant Mutant ◽  
Maternal Effect Genes

The product of the Drosophila easter gene, a member of the trypsin family of serine proteases, must be more active ventrally than dorsally to promote normal embryonic polarity. The majority of the easter protein in the embryo is present in the unprocessed zymogen form and appears to be evenly distributed in the extracellular space, indicating that the asymmetric activity of wild-type easter must arise post-translationally. A dominant mutant form of easter that does not require cleavage of the zymogen for activity (ea delta N) is active both dorsally and ventrally. The ea delta N mutant bypasses the requirement for five other maternal effect genes, indicating that these five genes exert their effects on dorsal-ventral patterning solely by controlling the activation of the easter zymogen. We propose that dorsal-ventral asymmetry is initiated by a ventrally-localized molecule in the vitelline membrane that nucleates an easter zymogen activation complex, leading to the production of ventrally active easter enzyme.

Sign in / Sign up

Export Citation Format

Share Document