Aneuploidy, a chromosomal numerical abnormality in the conceptus or fetus, occurs in at least 5% of all pregnancies and is the leading cause of early pregnancy loss in humans. Accumulating evidence now suggests that the correct segregation of chromosomes is affected by events occurring in prophase during meiosis I. These events include homologous chromosome pairing, sister-chromatid cohesion, and meiotic recombination. In our current study, we show that mutations in SYCP3, a gene encoding an essential component of the synaptonemal complex that is central to the interaction of homologous chromosomes, are associated with recurrent pregnancy loss. Two out of 26 women with recurrent pregnancy loss of unknown cause were found to carry independent heterozygous nucleotide alterations in this gene, neither of which was present among a group of 150 fertile women. Analysis of transcripts from minigenes harboring each of these two mutations revealed that both affected normal splicing, possibly resulting in the production of C-terminally mutated proteins. The mutant proteins were found to interact with their wild-type counterpart in vitro and inhibit the normal fiber formation of the SYCP3 protein when coexpressed in a heterologous system. These data suggest that these mutations are likely to generate an aberrant synaptonemal complex in a dominant-negative manner and contribute to abnormal chromosomal behavior that might lead to recurrent miscarriage. Combined with the fact that similar mutations have been previously identified in two males with azoospermia, our current data suggest that sexual dimorphism in response to meiotic disruption occurs even in humans.

a b s t r a c tMarine dinoflagellates of the genus Dinophysis can produce toxins of the okadaic acid (OA) and pectenotoxin (PTX) groups. These lipophilic toxins accumulate in filter-feeding shellfish and cause an illness in consumers called diarrhetic shellfish poisoning (DSP). In 2008, a bloom of Dinophysis led to the closure of shellfish harvesting areas along the Texas coast, one of the first DSP-related closures in the U.S. This event resulted in a broad study of toxin production in isolates of Dinophysis spp. from U.S. waters. In the present study, we compared toxin profiles in geographical isolates of Dinophysis collected in the U.S. (Eel Pond, Woods Hole MA; Martha's Vineyard, MA; and Port Aransas Bay, Texas), and in those from Canada (Blacks Harbour, Bay of Fundy) and Chile (Reloncavi Estuary), when cultured in the laboratory under the same conditions. For each isolate, the mitochondrial cox1 gene was sequenced to assist in species identification. Strains from the northeastern U.S. and Canada were all assigned to Dinophysis acuminata, while those from Chile and Texas were most likely within the D. acuminata complex whereas precise species designation could not be made with this marker. Toxins were detected in all Dinophysis isolates and each isolate had a different profile. Toxin profiles of isolates from Eel Pond, Martha's Vineyard, and Bay of Fundy were most similar, in that they all contained OA, DTX1, and PTX2. The Eel Pond isolate also contained OA-D8 and DTX1-D7, and low levels (unconfirmed structurally) of DTX1-D8 and DTX1-D9. D. acuminata from Martha's Vineyard produced DTX1-D7, along with OA, DTX1, and PTX2, as identified in both the cells and the culture medium. D. acuminata from the Bay of Fundy produced DTX1 and PTX2, as found in both cells and culture medium, while only trace amounts of OA were detected in the medium. The Dinophysis strain from Texas only produced OA, and the one from Chile only PTX2, as confirmed in both cells and culture medium.Published by Elsevier Ltd.

Abstract:For many years, the study of toxic Dinophysis species was primarily restricted to field populations until it was recently demonstrated that some of these organisms can be mixotrophically cultured in the laboratory with the ciliate prey, Myrionecta rubra, which had previously been fed with cryptophytes of the genus Teleaulax and Geminigera. Here we investigated the influence of growth phase and light intensity on the production of diarrhetic shellfish poisoning (DSP) toxins and pectenotoxins (PTXs) in cultures of Dinophysis acuminata from the northeastern United States. The cell toxin content of okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-2 (PTX2), and the okadaic acid diol ester (OA-D8) varied significantly with growth phase under all light treatments, at 6 °C. Each toxin quota remained low during middle and late exponential phases, but significantly increased by mid-plateau phase. DTX1 and OA-D8 were variable through plateau phase, while OA and PTX2 significantly decreased as the culture aged. Although maximum toxin content was not achieved until middle plateau phase, the rate of toxin production was generally greatest during exponential growth. The low and relatively constant cellular toxin levels observed during exponential and early-plateau phase indicate a balance between toxin production and growth, whereas in the middle-plateau phase, toxin production continues even though the cells are no longer capable of dividing, leading to higher toxin quotas. Light was required for Dinophysis growth and the production of all toxins, however, there was no significant difference in growth rates or toxin quotas between the higher light treatments ranging from 65 to 300 μmol photons m −2 s −1. These results demonstrate that DSP production in D. acuminata is constitutive, and that specific toxins are differentially produced or accumulated during the cells' growth phase, possibly in response to changes to their environment.Please note that this is an author-produced PDF of an article accepted for publication following peer review. The definitive publisher-authenticated version is available on the publisher Web site 2 Research highlightsOA, DTX1, PTX2, and OA-D8 toxin quota remained low content during middle and late exponential phases, but significantly increased by mid-plateau phase. DTX1 and OA-D8 were variable through plateau phase, while OA and PTX2 significantly decreased as the culture aged. The rate of toxin production was generally greatest during exponential growth. A balance between toxin production and growth of Dinophysis during exponential growth, but unbalance during plateau phase, leading to higher toxin quotas. Light was required for Dinophysis growth and the production of all toxins, however, there was no significant difference in growth rates or toxin quotas between the higher light treatments ranging from 65 to 300 μmol photons m −2 s −1.