Papers of the Month
Intramural
By Janelle Weaver and Shruti Somai
Artificial intelligence may improve chemical screening in zebrafish
Automated analyses based on artificial intelligence (AI) could promote objectivity and standardization of toxicity screening in zebrafish embryos, according to researchers from the Division of Translational Toxicology.
The zebrafish is a vertebrate model organism that is widely used in scientific research, particularly developmental biology. However, screening chemicals by visually assessing changes in zebrafish embryos is time-consuming and lacks objectivity. An alternative approach that overcomes these hurdles is to use AI techniques, such as deep learning models that have been trained on images of zebrafish larvae.
As part of the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) project, researchers developed deep-learning models to support such image-based assessments. Specifically, they used images of embryos exposed to different chemicals for five days and trained models to classify 20 distinct changes and segment specific regions of interest, including the head, tail, bladder, and yolk sac. This automated approach resulted in accurate classification of zebrafish larvae and robust identification of regions of interest for most images, potentially allowing expert screeners to focus their efforts on more challenging images.
According to the authors, their AI-based approach could allow researchers to rapidly and reliably evaluate changes in zebrafish larvae for developmental toxicity chemical screening. (JW)
Citation: Tandon A, Howard BE, Green AJ, Elmore R, Shah R, Merrick A, Shockley K, Ryan K, Hsieh JH. 2025. Artificial intelligence (AI)-driven morphological assessment of zebrafish larvae for developmental toxicity chemical screening. Aquat Toxicol 285:107415.
Understanding the origins of important but overlooked testicular cells
A protein called NR2F2 plays a crucial role in regulating testicular function by controlling the development of fetal Leydig cells, according to NIEHS researchers and their collaborators.
Testes include various cell types, such as fetal Leydig cells, which produce and secrete hormones that are important for male reproductive development. Impairments in the development of these cells can result in ambiguous genitalia, improper location of the urethral opening, undescended testicles, and infertility. Yet relatively little is known about the origin and development of fetal Leydig cells.
To fill this knowledge gap, the researchers analyzed cells in the embryonic mouse testis and used single-nucleus multiomics. They identified cell populations that give rise to mature fetal Leydig cells and pinpointed the molecular mechanisms underlying this process of cell differentiation. In particular, cells containing a nuclear receptor called Nr2f2 serve as progenitors for fetal Leydig cells and regulate the appearance of this unique cell type.
Deletion of Nr2f2 in mouse testes led to insufficient testosterone production, ambiguous genitalia, improper location of the urethral opening, and undescended testicles — features found in humans with Nr2f2 mutations. According to the authors, the study reveals molecular targets for diagnosing and treating Nr2f2-associated conditions affecting male reproduction. (JW)
Citation: Estermann MA, Grimm SA, Kitakule AS, Rodriguez KF, Brown PR, McClelland K, Amato CM, Yao HH. 2025. NR2F2 regulation of interstitial cell fate in the embryonic mouse testis and its impact on differences of sex development. Nat Commun 29;16(1):3987.
Phthalates and substitutes may influence blood pressure during pregnancy
Exposure during pregnancy to mixtures of chemicals used in plastic products such as food packaging may raise the risk of developing high blood pressure disorders, according to NIEHS researchers and their collaborators.
Phthalates are a group of chemicals commonly found in items like food packaging, cleaning products, and personal care items. These hormone-disrupting chemicals have been linked to adverse pregnancy outcomes, including abnormal fetal growth and preterm birth. Some studies suggest that exposure to phthalates during pregnancy may increase the risk of preeclampsia — a serious condition involving high blood pressure that can affect both maternal and fetal health. Although some phthalates are being replaced with structurally similar alternatives, little is known about the safety of these substitutes during pregnancy.
To better understand the risks, the researchers examined how exposure to phthalates and similar replacement chemicals during pregnancy might affect blood pressure, or pregnancy-related high blood pressure disorders. They looked at both individual chemicals and mixtures in 291 pregnant participants from the Human Placenta and Phthalates Study. The researchers measured urinary levels of 18 phthalate and replacement metabolites at different time points during pregnancy and tracked blood pressure to diagnose hypertensive disorders. They found a strong link between early pregnancy exposure to a specific chemical group — di-isononyl phthalate (DiNP) and other high molecular weight phthalate metabolites — and a higher risk of developing hypertensive disorders. This association was only seen with exposure during early pregnancy, not with overall exposure throughout pregnancy.
Together, these findings indicate that exposure to certain chemicals in everyday consumer products, such as phthalates and their replacements — especially during the early stages of pregnancy — may increase the risk of pregnancy-related high blood pressure conditions. (SS)
Citation: McNell EE, Stevens DR, Welch BM, Rosen EM, Fenton S, Calafat AM, Botelho JC, Sinkovskaya E, Przybylska A, Saade G, Abuhamad A, Ferguson KK. 2025. Exposure to phthalates and replacements during pregnancy in association with gestational blood pressure and hypertensive disorders of pregnancy. Environ Res 279(Pt 1):121739.
Bedroom allergens may contribute to poor sleep
Elevated levels of bedroom allergens are linked to sleep problems, according to NIEHS researchers and their collaborators.
Sleep problems are rising in prevalence and are associated with health conditions such as obesity, type 2 diabetes, and cardiovascular disease. Past research has focused on the impact of the outdoor environment on sleep health, but limited evidence hints at the potential importance of the indoor environment. For instance, the sleep microenvironment — the mattress, bed frame, bedding, pillows, and the air surrounding them — can contain indoor allergens from dust mites, pets, pests, and fungi. The allergens are common exposures in U.S. bedrooms and can contribute to upper and lower respiratory problems or discomfort (such as congestion, sneezing, coughing, wheezing, and breathlessness), which may contribute to sleep disordered breathing and other sleep disturbances.
To investigate the link between bedroom allergen exposure and sleep health, the researchers analyzed data from a nationally representative sample of 3,399 adults. To ensure objective measurement, the researchers analyzed bed and bedroom floor dust samples that were collected at each participant’s home. Elevated exposure to pet allergens was associated with trouble sleeping among Hispanic/Latino participants. Elevated exposure to fungal allergens was linked to sleep disorders among individuals with moderate socioeconomic status, and more sleep medication use among Hispanic/Latino participants. In addition, elevated exposure to pet and fungal allergens was associated with sleep disorders among women.
Given the high percentage of time spent in the bedroom, exposure to indoor allergens could represent a substantial, understudied contributing factor to poor sleep health, according to the authors. (JW)
Citation: Citation: Murkey JA, Wilkerson J, Salo PM, Thorne PS, Zeldin DC, Jackson CL. Indoor allergen exposure in relation to sleep health among US adults. 2025. J Allergy Clin Immunol Glob 4(2):100441.
(Janelle Weaver, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison. Shruti Somai, Ph.D., is a visiting fellow in the Genome Integrity and Structural Biology Laboratory.)
