(142) The Impact of Short- and Long-Term Phthalate Exposure on Pituitary Hormones and Inflammatory Markers: Hallmarks of Early Female Reproductive Aging.

Yinka V. Ojo¹, Karen E. Weis¹, Mary Laws², Ramses Santacruz-Márquez², Jodi A. Flaws² and Lori T. Raetzman¹

1. Department of Molecular and Integrative Physiology.

2. Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Abstract Text:

Reproductive aging in humans is linked to phthalate exposure, but the effects of phthalates on the hypothalamic-pituitary-gonadal axis remain unclear. We studied the pituitary gland, which produces gonadotropins such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH). We hypothesized that di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DINP) increase pituitary hormones and inflammatory markers in aging female mice. Adult female CD-1 mice received corn oil (vehicle control) or varying concentrations of DEHP and DINP over 10 days, 9, and 15 months, respectively. Pituitary tissues were collected for RT-qPCR, cytokine array analysis, and immunohistochemistry, whereas serum samples were analyzed for FSH/LH ELISA. Neither acute nor 9-month phthalate exposure affected gonadotropin mRNA expression. At 15 months, DINP increased Lhb levels, and DEHP increased Fshb and Lhb mRNA levels compared to controls. Acute exposure to DEHP or DiNP reduced Il1b, but increased Il-18 and Tnf mRNA levels compared to controls, indicating a modulated inflammatory response. Long-term phthalate treatment significantly increased protein inflammatory markers without changing Il1b, Il18, and Tnfa mRNA levels compared to controls. These findings suggest that phthalate exposure alters inflammatory markers and gonadotropins in the pituitary, potentially influencing reproductive aging.  Supported by NIH R01ES034112 and a Toxicology Scholar Award from the University of Illinois Urbana-Champaign.