PMID- 34311058
OWN - NLM
STAT- MEDLINE
DCOM- 20211217
LR  - 20211217
IS  - 1873-1708 (Electronic)
IS  - 0890-6238 (Linking)
VI  - 104
DP  - 2021 Sep
TI  - A mixture of persistent organic pollutants detected in human follicular fluid 
      increases progesterone secretion and mitochondrial activity in human granulosa 
      HGrC1 cells.
PG  - 114-124
LID - S0890-6238(21)00117-9 [pii]
LID - 10.1016/j.reprotox.2021.07.009 [doi]
AB  - 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 
      3beta-hydroxysteroid dehydrogenase (3betaHSD) 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 3betaHSD, which is associated with the inner 
      mitochondrial membrane.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Krawczyk, Kinga
AU  - Krawczyk K
AD  - Laboratory of Physiology and Toxicology of Reproduction, Jagiellonian University, 
      Gronostajowa 9, 30-387 Krakow, Poland.
FAU - Marynowicz, Weronika
AU  - Marynowicz W
AD  - Laboratory of Physiology and Toxicology of Reproduction, Jagiellonian University, 
      Gronostajowa 9, 30-387 Krakow, Poland.
FAU - Gogola-Mruk, Justyna
AU  - Gogola-Mruk J
AD  - Laboratory of Physiology and Toxicology of Reproduction, Jagiellonian University, 
      Gronostajowa 9, 30-387 Krakow, Poland.
FAU - Jakubowska, Klaudia
AU  - Jakubowska K
AD  - Laboratory of Physiology and Toxicology of Reproduction, Jagiellonian University, 
      Gronostajowa 9, 30-387 Krakow, Poland.
FAU - Tworzydlo, Waclaw
AU  - Tworzydlo W
AD  - Department of Developmental Biology and Invertebrate Morphology, Jagiellonian 
      University, Gronostajowa 9, 30-387 Krakow, Poland.
FAU - Opydo-Chanek, Malgorzata
AU  - Opydo-Chanek M
AD  - Laboratory of Experimental Hematology, Institute of Zoology and Biomedical 
      Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387 
      Krakow, Poland.
FAU - Ptak, Anna
AU  - Ptak A
AD  - Laboratory of Physiology and Toxicology of Reproduction, Jagiellonian University, 
      Gronostajowa 9, 30-387 Krakow, Poland. Electronic address: anna.ptak@uj.edu.pl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210724
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Steroids)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Endocrine Disruptors/metabolism
MH  - Estradiol/metabolism
MH  - Female
MH  - Follicular Fluid/chemistry/*metabolism
MH  - Granulosa Cells/drug effects
MH  - Humans
MH  - Luteinization/drug effects
MH  - Mitochondria/drug effects
MH  - Ovarian Neoplasms
MH  - Persistent Organic Pollutants/*metabolism/toxicity
MH  - Progesterone/*metabolism
MH  - Steroids/metabolism
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - Glucose uptake
OT  - Glycolysis
OT  - Granulosa cells
OT  - Mitochondrial activity
OT  - Mixture of endocrine-disrupting chemicals
OT  - Steroidogenesis
EDAT- 2021/07/27 06:00
MHDA- 2021/12/18 06:00
CRDT- 2021/07/26 20:12
PHST- 2021/05/10 00:00 [received]
PHST- 2021/06/28 00:00 [revised]
PHST- 2021/07/21 00:00 [accepted]
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/12/18 06:00 [medline]
PHST- 2021/07/26 20:12 [entrez]
AID - S0890-6238(21)00117-9 [pii]
AID - 10.1016/j.reprotox.2021.07.009 [doi]
PST - ppublish
SO  - Reprod Toxicol. 2021 Sep;104:114-124. doi: 10.1016/j.reprotox.2021.07.009. Epub 
      2021 Jul 24.