Fetal and Infant Effects of Maternal Opioid Use during Pregnancy: A Literature Review including Clinical, Toxicological, Pharmacogenomic, and Epigenetic Aspects for Forensic Evaluation.

The two primary classes of opioid substances are morphine and its synthetic derivative, heroin. Opioids can cross the placental barrier, reaching fetal circulation. Therefore, at any gestational age, the fetus is highly exposed to pharmacologically active opioid metabolites and their associated adverse effects. This review aimed to investigate all the studies reported in a timeframe of forty years about prenatal and postnatal outcomes of opioid exposition during pregnancy. Clinical and toxicological aspects, as well as pharmacogenetic and epigenetic research focusing on fetal and infant effects of opioid use during pregnancy together with their medico-legal implications are exposed and discussed.

Accumulation of Y-specific satellite DNAs during the evolution of Rumex acetosa sex chromosomes.

The study of the molecular structure of young heteromorphic sex chromosomes of plants has shed light on the evolutionary forces that control the differentiation of the X and Y during the earlier stages of their evolution. We have used the model plant Rumex acetosa, a dioecious species with multiple sex chromosomes, 2n = 12 + XX female and 2n = 12 + XY(1)Y(2) male, to analyse the significance of repetitive DNA accumulation during the differentiation of the Y. A bulk segregant analysis (BSA) approach allowed us to identify and isolate random amplified polymorphic DNA (RAPD) markers linked to the sex chromosomes. From a total of 86 RAPD markers in the parents, 6 markers were found to be linked to the Ys and 1 to the X. Two of the Y-linked markers represent two AT-rich satellite DNAs (satDNAs), named RAYSII and RAYSIII, that share about 80% homology, as well as with RAYSI, another satDNA of R. acetosa. Fluorescent in situ hybridisation demonstrated that RAYSII is specific for Y(1), whilst RAYSIII is located in different clusters along Y(1) and Y(2). The two satDNAs were only detected in the genome of the dioecious species with XX/XY(1)Y(2) multiple sex chromosome systems in the subgenus Acetosa, but were absent from other dioecious species with an XX/XY system of the subgenera Acetosa or Acetosella, as well as in gynodioecious or hermaphrodite species of the subgenera Acetosa, Rumex and Platypodium. Phylogenetic analysis with different cloned monomers of RAYSII and RAYSIII from both R. acetosa and R. papillaris indicate that these two satDNAs are completely separated from each other, and from RAYSI, in both species. The three Y-specific satDNAs, however, evolved from an ancestral satDNA with repeating units of 120 bp, through intermediate satDNAs of 360 bp. The data therefore support the idea that Y-chromosome differentiation and heterochromatinisation in the Rumex species having a multiple sex chromosome system have occurred by different amplification events from a common ancestral satDNA. Since dioecious species with multiple XX/XY(1)Y(2) sex chromosome systems of the section Acetosa appear to have evolved from dioecious species with an XX/XY system, the amplification of tandemly repetitive elements in the Ys of the section Acetosa is a recent evolutionary process that has contributed to an increase in the size and differentiation of the already non-recombining Y chromosomes.

Cloning and characterization of dispersed repetitive DNA derived from microdissected sex chromosomes of Rumex acetosa.

Rumex acetosa is characterized by a multiple chromosome system (2n = 12 + XX for females, and 2n = 12 + XY1Y2 for males), in which sex is determined by the ratio between the number of X chromosomes and autosome sets. For a better understanding of the molecular structure and evolution of plant sex chromosomes, we have generated a sex chromosome specific library of R. acetosa by microdissection. The screening of this library has allowed us to identify 5 repetitive DNA families that have been characterized in detail. One of these families, DOP-20, has shown no homology with other sequences in databases. Nevertheless, the putative proteins encoded by the other 4 families, DOP-8, DOP-47, DOP-60, and DOP-61, show homology with proteins from different plant retroelements, including poly proteins from Ty3-gypsy- and Ty1-copia-like long terminal repeat (LTR) retroelements, and reverse transcriptase from non-LTR retro elements. Results indicate that sequences from these 5 families are dispersed throughout the genome of both males and females, but no appreciable accumulation or differentiation of these types of sequences have been found in the Y chromosomes. These repetitive DNA sequences are more conserved in the genome of other dioecious species such as Rumex papillaris, Rumex intermedius, Rumex thyrsoides, Rumex hastatulus, and Rumex suffruticosus, than in the polygamous, gynodioecious, or hermaphrodite species Rumex induratus, Rumex lunaria, Rumex con glom er atus, Rumex crispus, and Rumex bucephalo phorus, which supports a single origin of dioecious species in this genus. The implication of these transposable elements in the origin and evolution of the heteromorphic sex chromosomes of R. acetosa is discussed.