Economics of Fertility Care.

Family building is a human right. The high cost and lack of insurance coverage associated with fertility treatments in the United States have made treatment inaccessible for many patients. The universal uptake of "add-on" services has further contributed to high out-of-pocket costs. Expansion in access to infertility care has occurred in several states through implementation of insurance mandates, and more employers are offering fertility benefits to attract and retain employees. An understanding of the economic issues shaping fertility should inform future policies aimed at promoting evidence-based practices and improving access to care in the United States.

An epigenetic synopsis of parental substance use.

The rate of substance use is rising, especially among reproductive-age individuals. Emerging evidence suggests that paternal pre-conception and maternal prenatal substance use may alter offspring epigenetic regulation (changes to gene expression without modifying DNA) and outcomes later in life, including neurodevelopment and mental health. However, relatively little is known due to the complexities and limitations of existing studies, making causal interpretations challenging. This review examines the contributions and influence of parental substance use on the gametes and potential transmissibility to the offspring's epigenome as possible areas to target public health warnings and healthcare provider counseling of individuals or couples in the pre-conception and prenatal periods to ultimately mitigate short- and long-term offspring morbidity and mortality.

More people, especially those of reproductive age, are using substances, and there is growing evidence to suggest that parental substance use before and during pregnancy may adversely affect offspring and result in issues later in life, including mental health challenges. Such relationships have been demonstrated with nicotine, alcohol, cannabis, opioids and illegal drugs (e.g., heroin, cocaine, methamphetamines). Some of these adverse impacts on offspring can potentially be passed down in families even after parents have quit using the substance. Because more individuals are using drugs, especially during the COVID-19 pandemic, it is important that families learn more about the potential impact of substance use on their future offspring before they try to get pregnant.

Cannabis and Pregnancy: A Review.

Importance: Prenatal cannabis use is rising and is a major public health issue. Cannabis use in pregnancy and during lactation has been associated with increased maternal and offspring morbidity and mortality. Objective: This review aims to summarize the existing literature and current recommendations for cannabis use during pregnancy or lactation. Evidence Acquisition: A PubMed, Cochrane Library, and Google Scholar literature search using the following terms was performed to gather relevant data: "cannabis," "cannabinoid," "delta-9-tetrahydrocannabinol," "THC," "cannabidiol," "fetal outcomes," "perinatal outcomes," "pregnancy," and "lactation." Results: Available studies on cannabis use in pregnancy and during lactation were reviewed and support an association with increased risk of preterm birth, neonatal intensive care unit admission, low birth weight, and small-for-gestational-age infants. Conclusion and Relevance: There is a critical need for research on the effects of cannabis use in pregnancy and during lactation. This is a necessary first step before furthering patient education, developing interventions, and targeting antenatal surveillance to ameliorate the adverse impacts on maternal and fetal health.

PACAP and acetylcholine cause distinct Ca2+ signals and secretory responses in chromaffin cells.

The adrenomedullary chromaffin cell transduces chemical messages into outputs that regulate end organ function throughout the periphery. At least two important neurotransmitters are released by innervating preganglionic neurons to stimulate exocytosis in the chromaffin cell-acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is widely acknowledged as an important secretagogue in this system, the pathway coupling PACAP stimulation to chromaffin cell secretion is poorly understood. The goal of this study is to address this knowledge gap. Here, it is shown that PACAP activates a Gαs-coupled pathway that must signal through phospholipase C ε (PLCε) to drive Ca2+ entry and exocytosis. PACAP stimulation causes a complex pattern of Ca2+ signals in chromaffin cells, leading to a sustained secretory response that is kinetically distinct from the form stimulated by ACh. Exocytosis caused by PACAP is associated with slower release of peptide cargo than exocytosis stimulated by ACh. Importantly, only the secretory response to PACAP, not ACh, is eliminated in cells lacking PLCε expression. The data show that ACh and PACAP, acting through distinct signaling pathways, enable nuanced and variable secretory outputs from chromaffin cells.

Identification of a pro-angiogenic functional role for FSP1-positive fibroblast subtype in wound healing.

Fibrosis accompanying wound healing can drive the failure of many different organs. Activated fibroblasts are the principal determinants of post-injury pathological fibrosis along with physiological repair, making them a difficult therapeutic target. Although activated fibroblasts are phenotypically heterogeneous, they are not recognized as distinct functional entities. Using mice that express GFP under the FSP1 or αSMA promoter, we characterized two non-overlapping fibroblast subtypes from mouse hearts after myocardial infarction. Here, we report the identification of FSP1-GFP+ cells as a non-pericyte, non-hematopoietic fibroblast subpopulation with a predominant pro-angiogenic role, characterized by in vitro phenotypic/cellular/ultrastructural studies and in vivo granulation tissue formation assays combined with transcriptomics and proteomics. This work identifies a fibroblast subtype that is functionally distinct from the pro-fibrotic αSMA-expressing myofibroblast subtype. Our study has the potential to shift our focus towards viewing fibroblasts as molecularly and functionally heterogeneous and provides a paradigm to approach treatment for organ fibrosis.