Biology subjects

Harbolic, A.

Publications and source records attributed to Harbolic, A..

3 recordsLinked to original sources

bioRxiv2026

Polystyrene Nanoplastics Disrupt Mouse Placenta Development in a Sex-Dependent Manner

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 (TGF{beta}) 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 euthanization 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 we separated by sex, only the male decidua were significantly decreased in the 200 nm group. Gene expression analysis of key signaling factors in the TGF{beta} pathway identified increased expression of Smad2 and Smad3, which may be suppressing prolactin and estrogen receptor signaling. Overall, both particle sizes disrupted placenta structure and signaling in a sex-dependent manner and may be acting as endocrine disruptors.

pharmacology and toxicology↗

bioRxiv2025

Polystyrene and polyethylene terephthalate nanoplastics differentially impact mouse ovarian follicle function

Exposure to micro- and nanoplastics is unavoidable. Foods and beverages contain plastic particles from environmental contamination and processing and packaging materials, which are frequently made of polyethylene terephthalate (PET). Micro- and nanoplastics have been detected in human tissues such as the brain, liver, and placenta, as well as in ovarian follicular fluid, but little is known about the effects nanoplastics have on the female reproductive system. In addition, few studies on the health impacts of nanoplastics have been performed using environmentally relevant plastic types and concentrations. Thus, this research tested the hypothesis that nanoplastics made of spherical polystyrene (PS), a common model nanoplastic, would have different effects on cultured mouse ovarian follicles compared to secondary PET nanoplastics at environmentally relevant doses. The ovary is a highly sensitive reproductive organ responsible for the development of follicles, which contain the oocyte, and production of steroid hormones. Follicles were harvested from adult mouse ovaries and cultured for 96 h with vehicle, spherical commercially available 200 nm PS nanoplastics (1-100 {micro}g/mL), or lab-generated 240 nm PET nanoplastics (0.1-10 {micro}g/mL). PS and PET nanoplastic exposure inhibited follicle growth and altered expression of genes related to steroid synthesis, cell cycle, and oxidative stress. PET nanoplastics increased levels of pregnenolone and decreased expression of Cyp17a1. Overall, both plastic types altered ovarian function, but they impacted different genes in similar pathways. These findings suggest that nanoplastic exposure at environmentally relevant concentrations may pose a risk to female reproductive health by disrupting hormonal and molecular pathways. In addition, environmentally relevant plastic types and doses are necessary for studying health impacts of nanoplastics. HighlightsO_LINanoplastics disrupted ovarian function in vitro C_LIO_LISecondary PET and virgin PS differently inhibited follicle growth and ovarian gene expression C_LIO_LIPET exposure increased pregnenolone, impacting steroid hormone pathways C_LIO_LIEnvironmentally relevant plastics can harm female reproductive health C_LI

pharmacology and toxicology↗

bioRxiv2024

A common phthalate replacement disrupts ovarian function in young adult mice

Di-2-ethylhexyl terephthalate (DEHTP) is a replacement for its structural isomer di-2-ethylhexyl phthalate (DEHP), a known endocrine disrupting chemical and ovarian toxicant. DEHTP is used as a plasticizer in polyvinyl chloride products and its metabolites are increasingly found in biomonitoring studies at levels similar to phthalates. However, little is known about the effects of DEHTP on the ovary. In this research, we tested the hypothesis that DEHTP is an ovarian toxicant and likely endocrine disrupting chemical like its isomer DEHP. The impact of environmentally relevant exposure to DEHTP and/or its metabolite mono-2-ethylhexyl terephthalate (MEHTP) on the mouse ovary was investigated in vivo and in vitro. For the in vivo studies, young adult CD-1 mice were orally dosed with vehicle, 10 {micro}g/kg, 100 {micro}g/kg, or 100 mg/kg of DEHTP for 10 days. For the in vitro studies, isolated untreated ovarian follicles were exposed to vehicle, 0.1, 1, 10, or 100 {micro}g/mL of DEHTP or MEHTP. Follicle counts, hormone levels, and gene expression of steroidogenic enzymes, cell cycle regulators, and apoptosis factors were analyzed. In vivo, DEHTP exposure increased primordial follicle counts at 100 {micro}g/kg and 100 mg/kg and decreased primary follicle counts at 100 mg/kg compared to control. DEHTP exposure also decreased expression of cell cycle regulators and apoptotic factors compared to control. In vitro, follicle growth was reduced by 1 {micro}g/mL DEHTP and 1, 10, and 100 {micro}g/mL MEHTP compared to controls, and expression of the cell cycle regulator Cdkn2b was increased. Steroid hormone levels and steroidogenic enzyme gene expression trended toward decreases in vivo, whereas progesterone was significantly increased by exposure to 100 {micro}g/mL MEHTP in vitro. Overall, these results suggest that DEHTP and MEHTP may be ovarian toxicants at low doses and should be subjected to further scrutiny for reproductive toxicity due to their similar structures to phthalates.

pharmacology and toxicology↗