Biology subjects

Baker, J. C.

Publications and source records attributed to Baker, J. C..

5 recordsLinked to original sources

bioRxiv2026

Potential Role of Nociceptin/Orphanin FQ in the Progression of Multiple Sclerosis

We showed before that the endogenous peptide Nociceptin blocks the premature differentiation of oligodendrocytes (OLGs), preventing untimely precocious myelination in the developing brain. Consistent with this early function, Nociceptin brain expression is developmentally regulated, sharply decreasing with the initiation and progression of myelination. However, we now found that at difference with controls and relapsing-remitting multiple sclerosis (RRMS), Nociceptin levels are highly elevated in cerebrospinal fluid from patients with the most severe progressive MS (PMS) forms. This questioned whether Nociceptin early developmental effects could be latter recapitulated, interfering with remyelination in PMS. This possibility was tested by inducing experimental autoimmune encephalomyelitis in older mice, at an age equivalent to that with increased risk of RRMS transition into PMS. Older animals develop persistently highly debilitating clinical symptoms, and display both brain and spinal cord demyelination. Importantly, these mice exhibit elevated brain Nociceptin levels, and their treatment with an antagonist of the Nociceptin receptor (NOR) elicits a regression of clinical scoring that is accompanied by higher ratios of OLGs/OLG progenitor cells, increased myelination, and reduction of reactive astrocytes. These findings suggest that Nociceptin may be a crucial player in the age-related progression of MS; interfering with OLG maturation and remyelination, and perhaps further exacerbating neurological dysfunction by targeting astrocyte populations. The upregulation of Nociceptin secretion by human astrocytes in response to proinflammatory cytokines, also points to this peptide as a mediator of microglia-astrocyte interactions supporting MS progression with aging. NOR may offer a novel pharmacological target for ameliorating the devastating effects of MS progression.

neuroscience↗

bioRxiv2025

Endogenous retrovirus IAP forms virus-like particles and traffics across the maternal-fetal barrier

For 50 years, virus-like particles (VLPs) have been observed in the placentas of many species, but their source and function remain unexplored. Here, we identify intracisternal a-type particle (IAP) elements, specifically the IAPEz-int family, as the likely source of VLPs in the mouse placenta. IAPEz-int instances are expressed throughout placentation and contain intact gag and env sequences critical for the formation of immature and mature particles, respectively. To elucidate a role for IAPEz-int derived VLPs in the mouse placenta, we generated a knock-in mouse containing a full-length element tagged with HA/FLAG. Using this line, we demonstrate that fetal IAPEz-int traffics into and across the maternal decidua. In total, we suggest that placental VLPs derive from IAPEz-int, and demonstrate their potential to traffic into maternal tissues, suggesting a role for these structures in maternal-fetal communication at the placental interface.

developmental biology↗

bioRxiv2023

Recent evolution of large offspring size and post-fertilization nutrient provisioning in swordtails

Organisms have evolved diverse reproductive strategies that impact the probability that their offspring survive to adulthood. Here, we describe divergence in reproductive strategy between two closely related species of swordtail fish (Xiphophorus). Swordtail fish and their relatives have evolved viviparity: they have internal fertilization and give birth to fully developed fry. We find that one species, X. malinche, which lives in high-elevation environments, has evolved larger offspring than its closest relative X. birchmanni and dwarfs the offspring size of other species in the genus. The larger fry of X. malinche are more resilient to starvation than their X. birchmanni relatives, hinting that the evolution of large offspring size may be an adaptation to the particularly challenging environments in which X. malinche are born. We find evidence that X. malinche achieves larger offspring size in part by continuing to provision their offspring over the course of embryonic development after fertilization, the first time this process has been documented in the Xiphophorus genus. Moreover, we observe differential regulation in the ovary of genes associated with maternal nutrient provisioning in other species that use this reproductive strategy. Intriguingly, these reproductive differences may drive an asymmetric hybrid incompatibility, since X. birchmanni mothers pregnant with F1 embryos give birth to premature and stillborn fry at an exceptionally high rate.

evolutionary biology↗

bioRxiv2022

Uterine injury during diestrus leads to embryo spacing defects and perturbations in the COX pathway in subsequent pregnancies

Uterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at approximately 30% of deliveries in the US and that are projected to continue to climb, a deeper understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are needed. However, there are no animal models to date that comprehensively assess the consequences of uterine injury. Here we describe a rodent model of uterine injury on subsequent in utero outcomes. We observed three distinct phenotypes: increased rates of resorption and death, embryo spacing defects, and placenta accreta-like features of reduced decidua and expansion of invasive trophoblasts. We show that the appearance of embryo spacing defects depends entirely on the phase of estrous cycle at the time of injury. Using RNA-seq, we identified perturbations in the expression of components of the COX/prostaglandin pathway after recovery from injury, a pathway that has previously been demonstrated to play an important role in embryo spacing. Therefore, we demonstrate that uterine damage in this mouse model causes morphological and molecular changes, most notably perturbed expression of COX/prostaglandin pathway-related genes, that ultimately lead to placental and embryonic developmental defects.

developmental biology↗

bioRxiv2020

PRG2 and AQPEP are misexpressed in fetal membranes in placenta previa and percreta

The obstetrical conditions placenta accreta spectrum (PAS) and placenta previa are a significant source of pregnancy-associated morbidity and mortality, yet the specific molecular and cellular underpinnings of these conditions are not known. In this study, we identified misregulated gene expression patterns in tissues from placenta previa and percreta (the most extreme form of PAS) compared with control cases. By comparing this gene set with existing placental single-cell and bulk RNA-Seq datasets, we show that the upregulated genes predominantly mark extravillous trophoblasts. We performed immunofluorescence on several candidate molecules and found that PRG2 and AQPEP protein levels are upregulated in both the fetal membranes and the placental disk in both conditions. While this increased AQPEP expression remains restricted to trophoblasts, PRG2 is mislocalized and is found throughout the fetal membranes. Using a larger patient cohort with a diverse set of gestationally aged-matched controls, we validated PRG2 as a marker for both previa and PAS and AQPEP as a marker for only previa in the fetal membranes membranes. Our findings suggest that the extraembryonic tissues surrounding the conceptus, including both the fetal membranes membranes and the placental disk, harbor a signature of previa and PAS that reflects increased trophoblast invasiveness. Summary sentence3SEQ and immunofluorescence reveal that extravillous trophoblast factors, most notably PRG2 and AQPEP, define the diseases placenta previa and placenta accreta spectrum (PAS) in both the chorioamniotic membranes and the placental disk.

pathology↗