Fetal health is heavily dictated by the maternal environment. Inhaling airborne pollutants, like particulate matter, is associated with pregnancy complications and fetal developmental pathologies, including fetal growth restriction (FGR). Because fetal growth is dependent on the placental transfer of nutrients from the maternal circulation, particularly glucose, investigating glucose transport capacity is critical to understanding the development of FGR associated with gestational inhalation of particulate matter. Pregnant Sprague Dawley rats were exposed to titanium dioxide nanoparticles (9.8±1.0 mg/m 3 ) as a proxy for ultrafine particulate matter, from gestational day (GD) 5 to GD 19 via whole-body inhalation. Glucose transporters (GLUTs) 1, 3 and 4 were evaluated in term placentas on GD 20 and ex vivo placental perfusion was conducted as a functional assessment of glucose transport. Exposure resulted in a reduction in Glut3 mRNA and GLUT1 protein. However, exposed placentas exhibited an adaptation, characterized by increased GLUT4 expression and membrane localization of both GLUT1 and GLUT4. Placental perfusion confirmed these molecular changes, revealing increased glucose flux in exposed placentas compared to control (AUC 95% CI: 77.4 to 127.5 vs 39.1 to 73.6, respectively). Contrary to our hypothesis, exposure to these nanoparticles enhanced glucose transport across the placenta. Here we have demonstrated that inhaling airborne pollutants during pregnancy modulates placental function and nutrient transport mechanisms, which can have direct effects on fetal development. Furthermore, we provide evidence for targeted interventions, aimed at mitigating fetal developmental pathologies. Highlights:Gestational inhalation of nanoparticles decreases GLUT1 expression in the placenta.The placenta adapts to gestational nanoparticle inhalation by enhancing GLUT4 expression and GLUT1 and GLUT4 membrane localization. Ex vivo placental perfusion demonstrated increased glucose flux across to the placenta to the fetus following gestational inhalation of nanoparticles.

Plastic production has been increasing exponentially. Throughout their lifespan, plastics degrade into smaller particles that accumulate in our bodies and the environment. Recent studies found these plastic particles can cross the placental barrier and reach the fetus. However, the impact of plastic particles on placental function is still unknown. We hypothesized that nanoplastics would disrupt placental growth and function, specifically focusing on transforming growth factor beta (TGFβ) signaling. To understand the impact of plastic particles on the placenta, we orally exposed pregnant CD-1 mice to 50 nm or 200 nm polystyrene plastic particles from gestation day 8 to day 15 at a human-relevant concentration of 5 mg/kg/day. After euthanasia on day 15, placenta and fetus weights were recorded, and tissues were prepared for histomorphology and gene expression analysis. We observed a statistically significant decrease in the area of the decidua in the placentas for the 200 nm treatment group and a borderline significant decrease in decidua area for the 50 nm treatment group compared to control. However, when separated by sex, only the male decidua were significantly decreased in the 200 nm group. Gene expression analysis of key signaling factors in the TGFβ pathway identified increased expression of Smad2 and Smad3, which may be suppressing estrogen receptor signaling. Overall, both particle sizes disrupted placenta structure and signaling in a sex-dependent manner.

Fetal health is heavily dictated by the maternal environment. Inhaling airborne pollutants, like particulate matter, is associated with pregnancy complications and fetal developmental pathologies, including fetal growth restriction (FGR). Because fetal growth is dependent on the placental transfer of nutrients from the maternal circulation, particularly glucose, investigating glucose transport capacity is critical to understanding the development of FGR associated with gestational inhalation of particulate matter. Pregnant Sprague Dawley rats were exposed to titanium dioxide nanoparticles (9.8 ± 1.0 mg/m3) to model occupational-level exposure to airborne particulates, from gestational day (GD) 5 to GD 19 via whole-body inhalation. Glucose transporters (GLUTs) 1, 3 and 4 were evaluated in term placentas on GD 20 and ex vivo placental perfusion was conducted as a functional assessment of glucose transport. Exposure resulted in a reduction in Glut3 mRNA and GLUT1 protein. However, exposed placentas exhibited a functional adaptation, characterized by increased GLUT4 expression and membrane localization of both GLUT1 and GLUT4. Placental perfusion confirmed these molecular changes, revealing increased glucose flux in exposed placentas compared to control (AUC 95% CI: 77.4 to 127.5 vs 39.1 to 73.6, respectively). Contrary to our hypothesis, exposure to these nanoparticles enhanced glucose transport across the placenta. Here we have demonstrated that inhaling airborne pollutants during pregnancy modulates placental function and nutrient transport mechanisms, which can have direct effects on fetal development. Furthermore, we provide evidence for targeted interventions, aimed at mitigating fetal developmental pathologies.

Plastics are ubiquitous in all trophic environments. Human exposures primarily occur via ingestion, inhalation, and/or injection routes. However, laboratory models of micro- and nanoplastic (MNP) particle exposures replicating the human condition remain inconsistent and uncharacterized, thus limiting study strength and compromising the reliability of results. The purpose of this study was to thoroughly optimize and characterize an established methodology for MNP rodent inhalation exposures, and to model particle respiratory deposition to estimate theoretical in silico exposures in rats and humans for the assessment of MNP health effects. Using our whole-body rodent inhalation facility, we generated MNP aerosols after thorough material characterization of a commercially available food-grade polyamide-12 (PA-12) bulk microparticle powder. PA-12 particulate was thoroughly assessed via pyrolysis–gas chromatography–mass spectrometry (PY-GC-MS), attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy, and helium ion microscopy (HIM) to confirm material chemistry, size, and surface shape. Representative MNP were established and measured at three mass concentrations, low (1.01 mg/m3 ± 0.17), mid- (5.05 mg/m3 ± 0.5), and high (9.98 mg/m3 ± 3.14) levels, representative of environmental and occupational exposure. The aerosol micro- and nanoparticle size distributions were measured and monitored in real-time with a scanning mobility particle sizer (SMPS), an aerodynamic particle sizer (APS), and a high-resolution electrical low-pressure impactor (HR-ELPI+) over a size range of 10 nm − 20 µm. Multi-day studies were conducted to assess intra- and inter-day variability in terms of several size distribution summary statistics. The merged data revealed a bi- and tri- modal distribution of particles with geometric mean diameters within the nano- and micro- size ranges for all concentrations. While commercial characterization reported an average size of 5 µm ±1, aerosol characterization in-house revealed MNP well within the nano-range, with average geometric mean of less than 200 nm and aerodynamic size peak mode values less than 100 nm at all concentrations. These data were entered into multiple-path particle dosimetry (MPPD©) model software to predict pulmonary anatomical deposition, which identified no significant differences between Sprague-Dawley rats and humans. Overall, we provide a thoroughly characterized methodology for controlled laboratory-based assessments to evaluate MNP toxicity and risk over a range of environmental and occupational doses. MPPD modeling of these exposures identifies pulmonary tract deposition within the human and rodent model, with no physiological differences between the low and high dose. This study provides a foundational methodology to assess the toxicological implications of MNP inhalation. Using our whole-body rodent inhalation facility, we generated MNP aerosols after thorough material characterization of a commercially available food-grade polyamide-12 (PA-12) bulk microparticle powder. PA-12 particulate was thoroughly assessed via pyrolysis–gas chromatography–mass spectrometry (PY-GC-MS), attenuated total reflectance–Fourier-transform infrared (ATR-FTIR) spectroscopy, and helium ion microscopy (HIM) to confirm material chemistry, size, and surface shape. Representative MNP were established and measured at three mass concentrations, low (1.01 mg/m3 ± 0.17), mid- (5.05 mg/m3 ± 0.5), and high (9.98 mg/m3 ± 3.14) levels, representative of environmental and occupational exposure. The aerosol micro- and nanoparticle size distributions were measured and monitored in real-time with a scanning mobility particle sizer (SMPS), an aerodynamic particle sizer (APS), and a high-resolution electrical low-pressure impactor (HR-ELPI+) over a size range of 10 nm – 20 µm. Multi-day studies were conducted to assess intra- and inter-day variability in terms of several size distribution summary statistics. The merged data revealed a bi- and tri- modal distribution of particles with geometric mean diameters within the nano- and micro- size ranges for all concentrations. While commercial characterization reported an average size of 5 µm ± 1, aerosol characterization in-house revealed MNP well within the nano-range, with average geometric mean of less than 200 nm and aerodynamic size peak mode values less than 100nm at all concentrations. These data were entered into multiple-path particle dosimetry (MPPD©) model software to predict pulmonary anatomical deposition, which identified no significant differences between Sprague-Dawley rats and humans. Overall, we provide a thoroughly characterized methodology for controlled laboratory-based assessments to evaluate MNP toxicity and risk over a range of environmental and occupational doses. MPPD modeling of these exposures identifies pulmonary tract deposition within the human and rodent model, with no physiological differences between the low and high dose. This study provides a foundational methodology to assess the toxicological implications of MNP inhalation.

Micro and nanoplastics (MNPs) are a ubiquitous environmental contaminant that humans are exposed through multiple routes. Multiple studies have demonstrated that MNPs deposit in human placental tissues and can translocate across the placental barrier. Maternal blood enters the placenta through uterine spiral arteries. During development of the placenta, trophoblasts enter the arteriolar lumen and invade the endothelial layer. This remodeling reduces vascular contractility and maintains maternal blood flow into the placenta. Simultaneously, the placenta increases surface area through angiogenic branching, facilitating the indirect contact of maternal and fetal blood spaces and promoting maternal-fetal exchange. To date, no groups have investigated how maternal MNP exposure affects these key steps of placentation. Therefore, in this study, pregnant Sprague Dawley rats were exposed to air containing polyamide-12 MNP throughout gestation. Placental morphology, invasion of spiral arteries, and angiogenic signaling were evaluated in male and female placentas at GD16 and GD20. Maternal MNP inhalation significantly reduced the relative distance of trophoblast invasion into the placental region that houses maternal spiral arteries. Additionally, MNP exposure increased staining of smooth muscle actin around maternal spiral arteries, indicating poor remodeling and likely reducing uteroplacental blood flow. Likewise, inhalation of MNPs altered the size and number of maternal and fetal blood spaces, favoring less surface area for maternal-fetal exchange. Lastly, significant changes in the expression and spatial distribution of angiogenic and antiangiogenic mRNAs that regulate vascular branching and surface area were observed. Future studies are needed to characterize the mechanisms by which polyamide-12 MNP influences placental hemodynamics.

Peripartum Cardiomyopathy (PPCM) is a leading cause of maternal death world-wide. It is diagnosed in the last month of pregnancy or 6 months after delivery as left ventricle systolic dysfunction, including significant (10 - 20%) reductions in ejection fraction and fractional shortening (-10%). While there is an association between particulate matter (PM) exposure and poor maternal cardiovascular health, little work has been done to elucidate PM’s role in the development of pregnancy-specific cardiovascular diseases like PPCM. Therefore, the purpose of this study was to characterize maternal cardiac structure and function and the risk of developing PPCM after gestational inhalation of nano-titanium dioxide (TiO 2 ), a surrogate for ultrafine PM. Using our custom whole-body rodent inhalation facility (IEStechno, Morgantown, WV), we exposed pregnant Sprague Dawley rats to nano-TiO 2 powder (Aeroxide, Parsippany, NJ) from gestational day (GD) 5 – GD 19 to occupationally-relevant concentrations of nano-TiO 2 (9.72 mg/m 3 ± 1.83). On GD 20, maternal heart structure and function were evaluated by cardiac ultrasound and morphometric analysis. Ultrasound of the maternal heart revealed significantly increased left ventricle mass (+22%) and length (+7%). Likewise, morphometric analysis revealed an enlargement of the left ventricle (97%), suggesting left ventricle dilation. Functionally, we identified left ventricle systolic dysfunction, reminiscent of the human PPCM phenotype, including clinically significant reductions in left ventricle ejection fraction (-10%) and fractional shortening (-14%).Overall, data demonstrates the development of a PPCM-like phenotype suggesting that gestational inhalation of PM may be a risk factor for disease development and/or progression. Future studies will aim to investigate the relationship between PM exposure and pregnancy driven hormonal changes in environmentally-induced PPCM to identify clinical biomarkers and therapeutic targets. Supported by: R01-ES-031285, P30-ES-005022, T32-ES-007148, Bristol Myers Squibb Fellowship, and Grover Foundation This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Despite the crucial role of the placenta in supporting pregnancy and fetal development, research into its susceptibility to environmental exposures has been limited by methodological challenges. We review diverse approaches to studying placental biology and responses to chemical exposures, and provide a comprehensive assessment of traditional and emerging methodologies. Beginning with an overview of placental biology and species differences, we evaluate in vivo and in vitro models, and discuss their strengths and limitations. We examine advances, including placental transfer models, toxicokinetic frameworks, and 3D microphysiological systems, for their potential to address current gaps. Last, we consider molecular epidemiology and high-throughput analyses as complementary strategies. Together, these tools support better experimental design and enhance our understanding of placental vulnerability to chemical exposures.

Micro and nanoplastic (MNP) detection in human tissues demonstrates that exposure at any life stage is inevitable. We have previously demonstrated that pulmonary exposure to this emerging environmental contaminant impairs endothelial function in the uterine vasculature of nonpregnant and pregnant rats. However, neither the mechanism of this dysfunction nor the role of the endothelial-derived vasodilator, nitric oxide (NO), have been interrogated. Therefore, we assessed uterine macro- and microvascular reactivity in Sprague Dawley rats to determine the mechanistic role of NO signaling in endothelial dysfunction after repeated (gestational day 5-19) MNP inhalation during pregnancy. Results identified that MNP exposure reduced fetal growth and impaired endothelial-dependent dilation in the uterine microcirculation, which control placental perfusion and resource availability to the fetus. Levels of activated endothelial nitric oxide synthase (eNOS), phosphorylated on Ser 1176 , were substantially decreased (<50%) in uterine vessels from exposed rats. This suggests MNP inhalation limited NO production and bioavailability. Endothelial function was partially restored by supplementation of arterial segments with the eNOS cofactor tetrahydrobiopterin (BH 4 ), demonstrating that exposed vessels were BH 4 -deficient. Partial restoration was also achieved by incubation with the reducing agent, DTT, suggesting that exposed vessels contained physiologically relevant levels of reactive oxygen and nitrogen species. Increased 3-nitrotyrosine residues and decreased thioredoxin protein expression further suggest MNP fosters nitrosative and oxidative stress in the uterine vasculature, impairing eNOS and endothelial-dependent dilation. These findings implicate eNOS uncoupling as a mechanistic basis for the vascular toxicity of MNPs and the adverse impact of MNPs on fetal development. This study reveals that repeated micro and nanoplastic (MNP) inhalation throughout gestation blunts endothelial-dependent dilation in the uterine microcirculation, promoting fetal growth restriction. Exposure impaired endothelial nitric oxide signaling through deactivating endothelial nitric oxide synthase (eNOS), reducing the availability of the eNOS cofactor tetrahydrobiopterin and producing a nitrosative and oxidative environment in uterine vascular tissue. These novel findings highlight the eNOS uncoupling as a key mechanism behind the fetal growth restriction induced by MNP.

Introduction Epidemiological and experimental studies support an association between exposure to particulate matter during pregnancy and the development of fetal growth restriction (FGR). The etiology of FGR is often attributed to poor nutrient delivery. Glucose is the primary energy substrate for fetal growth and an important energy source for placental tissue function; therefore, the health of the feto-placental unit depends on sufficient delivery of this nutrient to the tissue. Preeclampsia and FGR are associated with altered placental metabolism; moreover, the underlying causes and progression of these pathologies are influenced by fetal sex. The goal of this study was to investigate sex-related metabolic changes in the placenta after gestational exposure to particulate matter. Methods Sprague Dawley rats were exposed to nano-titanium dioxide (nano-TiO2) aerosols throughout pregnancy [gestational day (GD) 6-GD20]. For these studies, we developed a novel precision-cut placenta slice model for analysis of tissue bioenergetics using an Agilent Seahorse Analyzer. Results Exposure of pregnant rats to nano-TiO2 aerosols (9.74 ± 0.11 mg/m3) resulted in an overall decrease in placental metabolic function with an increased reliance on glycolytic ATP production. Reductions in maximum metabolic function were sex-related, revealing that female placentas are more sensitive to environmentally induced metabolic changes. Discussion These data show that there are sex-related mechanisms within the glycolytic pathway for increased glucose utilization. As increased metabolism of glucose by the placenta can reduce fetal glucose delivery, it may contribute to adverse effects on fetal growth induced by nano-TiO2.

Micro- and nanoplastics (MNPs) are a ubiquitous contaminant. Identification of MNPs in the human placenta suggests this toxicant poses a danger to developing offspring. Previously, we demonstrated that maternal pulmonary MNP exposure restricts fetal growth and disrupts fetoplacental cardiovascular function in rats. Herein, we investigated how repeated maternal inhalation of polyamide-12 MNP from gestational day 4-19 during pregnancy (10 mg/m3, geometric mean 175.8 ± 1.9 nm, mode particle size 19 nm, size range 6 nm-8 μm) in Sprague Dawley rats influences cardiovascular development and function in male and female offspring at gestational day 20, 2 weeks, 1 month and 3 months of age. Exposed neonates demonstrated decreased relative left ventricle wall thickness while dilation of the left ventricle was identified in MNP-exposed adolescents and adults. Analyses of offspring myocardial mRNA suggest that maternal MNP exposure disrupted mitochondrial function, calcium handling, and defense against oxidative species. MNP exposure increased blood flow velocity within the left ventricle, decreased fractional shortening, and increased relative cardiac output at the fetal, adolescent and adult stages, respectively. Although variable, select experimental outcomes were changed in a sexually dimorphic manner after gestational MNP.

Microplastics (MPs) and nanoplastics (NPs) are pervasive pollutants and their analyses by traditional mass spectrometric methods require time-intensive sample preparation (e.g., extraction, digestion, and separation). This study presents a rapid and novel method for detecting MPs and NPs using flame ionization mass spectrometry (FI-MS) in which a dried sample (e.g., powder, soil and tissue) is directly burnt or heated with a flame in front of the MS inlet. FI-MS enables decomposition and ionization of various plastics such as polyethylene terephthalate (PET) and polystyrene (PS), allowing for analysis to be completed as fast as 10 seconds per sample. As a demonstration of application of this technique, PET contaminants in 1 L of bottled water or in 0.65 L of apple juice contained in plastic bottles were quickly detected from a filter paper after sample filtration and brief drying. A 0.89 mg soil sample spiked with 6000 ppm PET microplastics was measured to contain 4.98 µg of PET (5595 ppm, quantitation error: 6.8 %). Strikingly, PS nanoplastics (200 nm size) in mouse placentas were successfully identified and quantified, highlighting the method's ability to analyze biological tissue without tedious sample preparation. Overall, this study demonstrates the high potential of FI-MS for real-world sample analysis of MPs and NPs in environmental, biological, or consumer product samples.

This study reveals that repeated micro and nanoplastic (MNP) inhalation throughout gestation blunts endothelial-dependent dilation in the uterine microcirculation, promoting fetal growth restriction. Exposure impaired endothelial nitric oxide signaling through deactivating endothelial nitric oxide synthase (eNOS), reducing the availability of the eNOS cofactor tetrahydrobiopterin, and producing a nitrosative and oxidative environment in uterine vascular tissue. These novel findings highlight the eNOS uncoupling as a key mechanism behind the fetal growth restriction induced by MNP.

Micro-nanoplastic particulates (MNPs) have been identified in both indoor and outdoor environments. From these real-world exposures, MNPs have been identified in human fluids and organ tissues, including the placenta and breastmilk. Laboratory studies have identified MNPs are capable of crossing the placental barrier and depositing in fetal tissues; however, it remained unclear if MNPs persist in offspring tissues after birth. Six pregnant Sprague-Dawley rats were divided equally into two groups: control and exposed to polyamide-12 (PA- 12) MNP aerosols (11.46 +/- 3.78 mg/m3) 3 ) over an average of 4.35 h +/- 0.39 for 10 non-consecutive days between gestational day (GD) 6 - GD 19, in our custom rodent exposure chamber, allowing for whole-body inhalation. Two-weeks after delivery in-house, offspring tissues (i.e. lung, liver, kidney, heart, brain) from 1 male and 1 female pup per litter were fixed in 4 % paraformaldehyde, sectioned, stained with hematoxylin and eosin, and assessed using hyperspectral dark-field microscopy. PA-12 MNPs were identified in all offspring tissues of the exposed dams. No MNPs were visualized in control tissues. These findings have important implications for human MNPs translocation, deposition, maternal/fetal health, and the developmental origins of health and disease. Further research is warranted to quantify MNPs mass deposition, biological accumulation, and systemic toxicity.

Engineered nanomaterials (ENM) are widely used in commercial, domestic, and more recently biomedical applications. While the majority of exposures to ENM are unintentional, biomedical platforms are being evaluated for use in individualized and/or tissue-targeted therapies. Treatments are often avoided during prenatal periods to reduce adverse effects on the developing fetus. The placenta is central to maternal-fetal medicine. Perturbation of placental functions can limit transfer of necessary nutrients, alter production of hormones needed during pregnancy, or allow undesired passage of xenobiotics to the developing fetus. The development of therapeutics to target specific maternal, placental, or fetal tissues would be especially important to reduce or circumvent toxicities. Therefore, this review will discuss the potential use of ENM in perinatal medicine, the applicable physiochemical properties of ENM in therapeutic use, and current methodologies of ENM testing in perinatal medicine, and identify maternal, fetal, and offspring concerns associated with ENM exposure during gestation. As potential nanoparticle-based therapies continue to develop, so does the need for thorough consideration and evaluation for use in perinatal medicine.

Large-scale production and waste of plastic materials have resulted in widespread environmental contamination by the breakdown product of bulk plastic materials to micro- and nanoplastics (MNPs). The small size of these particles enables their suspension in the air, making pulmonary exposure inevitable. Previous work has demonstrated that xenobiotic pulmonary exposure to nanoparticles during gestation leads to maternal vascular impairments, as well as cardiovascular dysfunction within the fetus. Few studies have assessed the toxicological consequences of maternal nanoplastic (NP) exposure; therefore, the objective of this study was to assess maternal and fetal health after a single maternal pulmonary exposure to polystyrene NP in late gestation. We hypothesized that this acute exposure would impair maternal and fetal cardiovascular function. Pregnant rats were exposed to nanopolystyrene on gestational day 19 via intratracheal instillation. 24 h later, maternal and fetal health outcomes were evaluated. Cardiovascular function was assessed in dams using vascular myography ex vivo and in fetuses in vivo function was measured via ultrasound. Both fetal and placental weight were reduced after maternal exposure to nanopolystyrene. Increased heart weight and vascular dysfunction in the aorta were evident in exposed dams. Maternal exposure led to vascular dysfunction in the radial artery of the uterus, a resistance vessel that controls blood flow to the fetoplacental compartment. Function of the fetal heart, fetal aorta, and umbilical artery after gestational exposure was dysregulated. Taken together, these data suggest that exposure to NPs negatively impacts maternal and fetal health, highlighting the concern of MNPs exposure on pregnancy and fetal development.

Plastics are now omnipresent in our daily lives. The existence of microplastics (1 µm to 5 mm in length) and possibly even nanoplastics (<1 μm) has recently raised health concerns. In particular, nanoplastics are believed to be more toxic since their smaller size renders them much more amenable, compared to microplastics, to enter the human body. However, detecting nanoplastics imposes tremendous analytical challenges on both the nano-level sensitivity and the plastic-identifying specificity, leading to a knowledge gap in this mysterious nanoworld surrounding us. To address these challenges, we developed a hyperspectral stimulated Raman scattering (SRS) imaging platform with an automated plastic identification algorithm that allows micro-nano plastic analysis at the single-particle level with high chemical specificity and throughput. We first validated the sensitivity enhancement of the narrow band of SRS to enable high-speed single nanoplastic detection below 100 nm. We then devised a data-driven spectral matching algorithm to address spectral identification challenges imposed by sensitive narrow-band hyperspectral imaging and achieve robust determination of common plastic polymers. With the established technique, we studied the micro-nano plastics from bottled water as a model system. We successfully detected and identified nanoplastics from major plastic types. Micro-nano plastics concentrations were estimated to be about 2.4 ± 1.3 × 10 5 particles per liter of bottled water, about 90% of which are nanoplastics. This is orders of magnitude more than the microplastic abundance reported previously in bottled water. High-throughput single-particle counting revealed extraordinary particle heterogeneity and nonorthogonality between plastic composition and morphologies; the resulting multidimensional profiling sheds light on the science of nanoplastics.

Pregnancy is a vulnerable life stage for the mother and developing fetus. Because of this dual concern, approved therapeutic options for pre-existing conditions or pregnancy-induced pathologies, placental deformities, or fetal concerns are extremely limited. These cases often leave patients and clinicians having to choose between maternal health and fetal development. Recent advancements in nanomedicine and nanotherapeutic devices have made the development of perinatal therapeutics an attractive objective. However, perinatal medicine requires a multifaceted approach given the interactions between maternal, placental, and fetal physiology. Maternal-fetal interactions are centralized to the placenta, a specialized transient barrier organ, to allow for nutrient and waste exchange. Perinatal nanotherapeutics must be designed for placental avoidance or uptake. In this review, pregnancy-related conditions, experimental models, and modes of drug delivery during pregnancy are discussed.