PMID- 28859905 OWN - NLM STAT- MEDLINE DCOM- 20190212 LR - 20190215 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 461 DP - 2018 Feb 5 TI - Atrazine suppresses FSH-induced steroidogenesis and LH-dependent expression of ovulatory genes through PDE-cAMP signaling pathway in human cumulus granulosa cells. PG - 79-88 LID - S0303-7207(17)30451-3 [pii] LID - 10.1016/j.mce.2017.08.015 [doi] AB - Atrazine (ATR) alters female reproductive functions in different animal species. Here, we analyzed whether ATR disturbs steroidogenic and ovulatory processes in hormone-stimulated human cumulus granulosa cells and mechanism of its action. Results showed that treatment of human cumulus granulosa cells with 20 muM ATR for 48 h resulted in lower FSH-stimulated estradiol and progesterone production. ATR reduced mRNA levels of aromatase (CYP19A1), steroidogenic acute regulatory protein (STAR) and luteinizing hormone/choriogonadotropin receptor (LHCGR). Addition of hCG 48 h after FSH and ATR treatment did not trigger maximal expression of the ovulatory genes amphiregulin (AREG) and epiregulin (EREG). Mechanistic experiments showed that ATR activated cPDE and decreased cAMP level. Addition of total PDE and specific PDE4 inhibitors, IBMX and rolipram, prevented ATR's action on CYP19A1 and STAR mRNA expression in FSH-stimulated human cumulus granulosa cells. This study suggests that ATR alters steroidogenesis and ovulatory process in human cumulus granulosa cells jeopardizing female reproduction. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Pogrmic-Majkic, Kristina AU - Pogrmic-Majkic K AD - Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Serbia. Electronic address: kristina.pogrmic@dbe.uns.ac.rs. FAU - Samardzija, Dragana AU - Samardzija D AD - Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Serbia. FAU - Stojkov-Mimic, Natasa AU - Stojkov-Mimic N AD - Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Serbia. FAU - Vukosavljevic, Jelena AU - Vukosavljevic J AD - Clinic for Gynecology and Obstetrics, Clinical Center of Vojvodina, Novi Sad, Serbia. FAU - Trninic-Pjevic, Aleksandra AU - Trninic-Pjevic A AD - Clinic for Gynecology and Obstetrics, Clinical Center of Vojvodina, Novi Sad, Serbia. FAU - Kopitovic, Vesna AU - Kopitovic V AD - Clinic for Gynecology and Obstetrics, Clinical Center of Vojvodina, Novi Sad, Serbia. FAU - Andric, Nebojsa AU - Andric N AD - Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Serbia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170830 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (Phosphodiesterase Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Steroids) RN - 1F7A44V6OU (Colforsin) RN - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate) RN - 4G7DS2Q64Y (Progesterone) RN - 4TI98Z838E (Estradiol) RN - 9002-67-9 (Luteinizing Hormone) RN - 9002-68-0 (Follicle Stimulating Hormone) RN - E0399OZS9N (Cyclic AMP) RN - EC 3.1.4.- (Phosphoric Diester Hydrolases) RN - K676NL63N7 (Rolipram) RN - QJA9M5H4IM (Atrazine) RN - TBT296U68M (1-Methyl-3-isobutylxanthine) SB - IM MH - 1-Methyl-3-isobutylxanthine/pharmacology MH - 8-Bromo Cyclic Adenosine Monophosphate/pharmacology MH - Atrazine/*toxicity MH - Cell Survival/drug effects MH - Colforsin/pharmacology MH - Cumulus Cells/drug effects/*metabolism MH - Cyclic AMP/*metabolism MH - Estradiol/biosynthesis MH - Female MH - Follicle Stimulating Hormone/*pharmacology MH - Gene Expression Regulation/drug effects MH - Humans MH - Luteinizing Hormone/*metabolism MH - Ovulation/drug effects/*genetics MH - Phosphodiesterase Inhibitors/pharmacology MH - Phosphoric Diester Hydrolases/*metabolism MH - Progesterone/biosynthesis MH - RNA, Messenger/genetics/metabolism MH - Rolipram/pharmacology MH - Signal Transduction/drug effects/genetics MH - Steroids/*biosynthesis OTO - NOTNLM OT - Atrazine OT - Human cumulus granulosa cells OT - Ovulatory processes OT - Steroidogenesis OT - cAMP/PDE EDAT- 2017/09/02 06:00 MHDA- 2019/02/13 06:00 CRDT- 2017/09/02 06:00 PHST- 2017/05/29 00:00 [received] PHST- 2017/07/13 00:00 [revised] PHST- 2017/08/28 00:00 [accepted] PHST- 2017/09/02 06:00 [pubmed] PHST- 2019/02/13 06:00 [medline] PHST- 2017/09/02 06:00 [entrez] AID - S0303-7207(17)30451-3 [pii] AID - 10.1016/j.mce.2017.08.015 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2018 Feb 5;461:79-88. doi: 10.1016/j.mce.2017.08.015. Epub 2017 Aug 30.