A mixture of persistent organic pollutants detected in human follicular fluid increases progesterone secretion and mitochondrial activity in human granulosa HGrC1 cells

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 104; pp. 114 - 124
• Main Authors: Krawczyk, Kinga, Marynowicz, Weronika, Gogola-Mruk, Justyna, Jakubowska, Klaudia, Tworzydło, Wacław, Opydo-Chanek, Małgorzata, Ptak, Anna
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2021
• Subjects: Endocrine Disruptors - metabolism; Estradiol - metabolism; Female; Follicular Fluid - chemistry; Follicular Fluid - metabolism; Glucose uptake; Glycolysis; Granulosa cells; Granulosa Cells - drug effects; Humans; Luteinization - drug effects; Mitochondria - drug effects; Mitochondrial activity; Mixture of endocrine-disrupting chemicals; Ovarian Neoplasms; Persistent Organic Pollutants - metabolism; Persistent Organic Pollutants - toxicity; Progesterone - metabolism; Steroidogenesis; Steroids - metabolism; Up-Regulation - drug effects; FF; DMSO; EDC; p,p’-DDE; OXPHOS; HK2; Mitochondrial activity; LDH; Glucose uptake; StAR; FBS; Granulosa cells; GC; GLUT1; HCB; 3βHSD; 2-DG; PFOA; PCB; ECAR; Mixture of endocrine-disrupting chemicals; Glycolysis; Steroidogenesis; GLUT4; PER; OCR; PFOS
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2021.07.009

•The EDC mixture increases progesterone secretion via 3βHSD in HGrC1 cells.•The EDC mixture increases mitochondrial activity and the ATP content.•The EDC mixture decreases glucose uptake and glucose transporter 4 expression.•The EDC mixture does not alter the glycolytic rate.•Glucose homeostasis is essential for the steroidogenic function of granulosa cells. Disruption of granulosa cells (GCs), the main functional cells in the ovary, is associated with impaired female fertility. Epidemiological studies demonstrated that women have detectable levels of organic pollutants (e.g., perfluorooctanoate, perfluorooctane sulfonate, 2,2-dichlorodiphenyldichloroethylene, polychlorinated biphenyl 153, and hexachlorobenzene) in their follicular fluid (FF), and thus these compounds may directly affect the function of GCs in the ovary. Considering that humans are exposed to multiple pollutants simultaneously, we elucidated the effects of a mixture of endocrine-disrupting chemicals (EDCs) on human granulosa HGrC1 cells. The EDC mixture directly increased progesterone secretion by upregulating 3β-hydroxysteroid dehydrogenase (3βHSD) expression. Furthermore, the EDC mixture increased activity of mitochondria, which are the central sites for steroid hormone biosynthesis, and the ATP content. Unexpectedly, the EDC mixture reduced glucose transporter 4 (GLUT4) expression and perturbed glucose uptake; however, this did not affect the glycolytic rate. Moreover, inhibition of GLUT1 by STF-31 did not alter the effects of the EDC mixture on steroid secretion but decreased basal estradiol secretion. Taken together, our results demonstrate that the mixture of EDCs present in FF can alter the functions of human GCs by disrupting steroidogenesis and may thus adversely affect female reproductive health. This study highlights that the EDC mixture elicits its effects by targeting mitochondria and increases mitochondrial network formation, mitochondrial activity, and expression of 3βHSD, which is associated with the inner mitochondrial membrane.