0 Ask Beta Account

Effects of prenatal exposure to hexafluoropropylene oxide dimer acid on rat and offspring mammary gland development and associated hormone levels

Libing Wang, Yuxin Lin, Wenchao Han, Lu Liu, Wendong Liu, Wenjing Zhu, Dongmei Jia, Zhugen Yang, Kui Che, K DALTON

  • Qingdao University ROR
  • Cranfield University ROR
  • University College Hospital ROR

Chemico-biological interactions, 430(12B), 111985

DOI 10.1016/j.cbi.2026.111985 PMID 41730328 Source

Abstract

Background

This study investigated the effects of prenatal exposure to hexafluoropropylene oxide dimer acid (HFPO-DA), a replacement for perfluorooctanoic acid (PFOA), on mammary gland development of both pregnant rats and their offspring, as well as its influence on related hormone levels.

Methods

Pregnant Sprague-Dawley (SD) rats were orally exposed to HFPO-DA at doses of 0, 1, 10, and 100 mg/kg/day from gestation day (GD) 0.5 to GD 19.5. On GD 19.5, half of the pregnant rats from each dose group underwent caesarean section, while the other half gave birth naturally. The offspring from the rats that gave birth naturally were raised until they reached postnatal day (PND) 21. The serum levels of progesterone (Pg), estradiol (E2), and prolactin (PRL) in the pregnant rats and their offspring on PND 21 were detected via ELISA (enzyme-linked immunosorbent assay). Changes in mammary glands of pregnant rats, their fetuses, and PND 21 offspring were assessed by haematoxylin and eosin (H&E) staining. The development of mammary gland tissue structures in fetuses and PND 21 offspring was evaluated using whole gland staining. Immunohistochemical staining was used to assess STAT5 expression in the mammary glands of pregnant rats and Ki67 expression in the mammary glands of fetuses and PND 21 offspring.

Results

In pregnant rats, exposure to HFPO-DA significantly increased the PRL levels. The expression of STAT5 was also significantly elevated in mammary epithelial cells. The lobular and alveolar areas expanded dose-dependently, and milk secretion was observed in the high-dose group. In fetuses and PND 21 offspring exposed to HFPO-DA, we observed significant growth of secondary mammary ducts, a substantial increase in ductal coverage area, ductal buds, and primary duct length, as well as an increase in Ki67 expression in mammary epithelial cells.

Conclusions

Collectively, these findings suggest that HFPO-DA exposure elevates serum PRL levels in pregnant rats, promotes lactation, and stimulates early-stage mammary gland development in offspring.

Topics

Reproductive Endocrinology > Environmental Exposures > PFAS ChemicalsReproductive Endocrinology > Hormone Disruption > ProlactinPregnancy > Prenatal Exposures > Chemical Toxicants
prenatal HFPO-DA exposure mammary gland development, hexafluoropropylene oxide dimer acid reproductive toxicity, PFAS replacement chemicals prenatal effects, HFPO-DA prolactin levels pregnant rats, mammary gland development fetal PFAS exposure, Liu 2026 HFPO-DA mammary gland, GenX chemicals endocrine disruption pregnancy, STAT5 expression mammary epithelial cells PFAS, Ki67 proliferation mammary duct offspring, environmental contaminants lactation hormones rat model, dose-dependent mammary lobular expansion chemical exposure, PFOA replacement reproductive endocrine effects
PMID 41730328 41730328 DOI 10.1016/j.cbi.2026.111985 10.1016/j.cbi.2026.111985

Cite this article

Dalton, K. (1981). The effect of progesterone and progestogens on the foetus. *Neuropharmacology*, *20*(12B), 1267-1269.

Keywords

Abnormalities, Drug-Induced/etiology, Behavior/drug Effects, Disorders of Sex Development/chemically Induced, Female, Fetus/drug Effects, Humans, Intelligence/drug Effects, Pregnancy, Prenatal Exposure Delayed Effects, Progesterone/adverse Effects, Progestins/adverse Effects, Receptors, Progesterone/drug Effects, Species Specificity, Progestins, Receptors, Progesterone, Progesterone