Time to synchronize our clocks: Connecting developmental mechanisms and evolutionary consequences of heterochrony

The bladder exstrophy–epispadias complex (BEEC) is an abdominal midline malformation comprising a spectrum of congenital genitourinary abnormalities of the abdominal wall, pelvis, urinary tract, genitalia, anus, and spine. The vast majority of BEEC cases are classified as non-syndromic and the etiology of this malformation is still unknown. This review presents the current knowledge on this multifactorial disorder, including phenotypic and anatomical characterization, epidemiology, proposed developmental mechanisms, existing animal models, and implicated genetic and environmental components.

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Boon and Bane of DNA Double-Strand Breaks

International Journal of Molecular Sciences ◽

10.3390/ijms22105171 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5171

Author(s):

Ingo Schubert

Keyword(s):

Negative Impact ◽

Biological Effects ◽

Double Strand Breaks ◽

Immunoglobulin Gene ◽

Dna Double Strand Breaks ◽

Endogenous Factors ◽

Strand Breaks ◽

Chromatin Elimination ◽

Evolutionary Consequences ◽

Cell Lethality

DNA double-strand breaks (DSBs), interrupting the genetic information, are elicited by various environmental and endogenous factors. They bear the risk of cell lethality and, if mis-repaired, of deleterious mutation. This negative impact is contrasted by several evolutionary achievements for DSB processing that help maintaining stable inheritance (correct repair, meiotic cross-over) and even drive adaptation (immunoglobulin gene recombination), differentiation (chromatin elimination) and speciation by creating new genetic diversity via DSB mis-repair. Targeted DSBs play a role in genome editing for research, breeding and therapy purposes. Here, I survey possible causes, biological effects and evolutionary consequences of DSBs, mainly for students and outsiders.

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Advanced maternal age perturbs mouse embryo development and alters the phenotype of derived embryonic stem cells

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174421000325 ◽

2021 ◽

pp. 1-11

Author(s):

Pooja Khurana ◽

Neil R. Smyth ◽

Bhavwanti Sheth ◽

Miguel A. Velazquez ◽

Judith J. Eckert ◽

...

Keyword(s):

Maternal Age ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cell ◽

Advanced Maternal Age ◽

Preimplantation Embryos ◽

Dependent Manner ◽

Ki 67 ◽

Altered Expression ◽

Developmental Potential ◽

Developmental Mechanisms

Abstract Advanced maternal age (AMA) is known to reduce fertility, increases aneuploidy in oocytes and early embryos and leads to adverse developmental consequences which may associate with offspring lifetime health risks. However, investigating underlying effects of AMA on embryo developmental potential is confounded by the inherent senescence present in maternal body systems further affecting reproductive success. Here, we describe a new model for the analysis of early developmental mechanisms underlying AMA by the derivation and characterisation of mouse embryonic stem cell (mESC-like) lines from naturally conceived embryos. Young (7–8 weeks) and Old (7–8 months) C57BL/6 female mice were mated with young males. Preimplantation embryos from Old dams displayed developmental retardation in blastocyst morphogenesis. mESC lines established from these blastocysts using conventional techniques revealed differences in genetic, cellular and molecular criteria conserved over several passages in the standardised medium. mESCs from embryos from AMA dams displayed increased incidence of aneuploidy following Giemsa karyotyping compared with those from Young dams. Moreover, AMA caused an altered pattern of expression of pluripotency markers (Sox2, OCT4) in mESCs. AMA further diminished mESC survival and proliferation and reduced the expression of cell proliferation marker, Ki-67. These changes coincided with altered expression of the epigenetic marker, Dnmt3a and other developmental regulators in a sex-dependent manner. Collectively, our data demonstrate the feasibility to utilise mESCs to reveal developmental mechanisms underlying AMA in the absence of maternal senescence and with reduced animal use.

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