PMID- 36166083
OWN - NLM
STAT- MEDLINE
DCOM- 20230321
LR  - 20230520
IS  - 1432-0711 (Electronic)
IS  - 0932-0067 (Linking)
VI  - 307
IP  - 4
DP  - 2023 Apr
TI  - Effects of chemotherapy on ovaries of pregnant mice.
PG  - 1163-1176
LID - 10.1007/s00404-022-06793-w [doi]
AB  - PURPOSE: It is unknown if future fertility is compromised by the administration 
      of chemotherapy during pregnancy. The aim of this study was to identify if 
      chemotherapy affects the maternal ovaries during pregnancy and whether these 
      effects depend on type of chemotherapy and duration of exposure. METHODS: 
      Pregnant 8-week-old female BL6 mice were exposed to 6 different single 
      chemotherapeutic agents (carboplatin, cisplatin, paclitaxel, epirubicin, 
      doxorubicin, or cyclophosphamide) or saline at gestational day (GD) 13.5. The 
      mice were sacrificed at GD 15.5 or GD 18.5. Ovaries were assessed by 
      histopathology and immunohistochemistry. Follicle count was determined per 
      follicle stage and per treatment modality. RESULTS: Maternal ovarian damage was 
      demonstrated by the presence of apoptosis and necrosis in preantral follicles. 
      The extent of this damage depends upon type of chemotherapy and duration of 
      exposure (2 or 5 days). After short exposure, 81% of ovaries showed 
      histopathologic signs of damage compared to 36% after long exposure, which might 
      suggest a transient effect. Loss of primordial follicles (PMFs) was observed 
      after both short and long exposure, with a reduction of more than 70%. Evidence 
      of DNA damage, as demonstrated by phospho-H2AX expression, was present in 23% 
      (range 0-89%) of PMFs exposed to chemotherapy, but only in the short exposure 
      group. Overall, the least damage was seen after administration of paclitaxel. 
      CONCLUSION: Despite physiological ovarian function suppression during gestation, 
      chemotherapy-induced damage of the ovaries occurs in pregnant mouse models, 
      potentially affecting future fertility.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Schuurman, Teska
AU  - Schuurman T
AUID- ORCID: 0000-0001-8540-2030
AD  - Department of Gynecologic Oncology, Netherlands Cancer Institute, Antoni Van 
      Leeuwenhoek, Amsterdam, The Netherlands.
FAU - Song, Ji-Ying
AU  - Song JY
AUID- ORCID: 0000-0002-6296-1996
AD  - Department of Experimental Animal Pathology, Netherlands Cancer Institute, 
      Amsterdam, The Netherlands.
FAU - Wolters, Vera
AU  - Wolters V
AUID- ORCID: 0000-0002-0169-3262
AD  - Department of Gynecologic Oncology, Netherlands Cancer Institute, Antoni Van 
      Leeuwenhoek, Amsterdam, The Netherlands.
FAU - van de Ven, Marieke
AU  - van de Ven M
AUID- ORCID: 0000-0001-6779-9353
AD  - Mouse Clinic for Cancer and Aging (MCCA), Preclinical Intervention Unit, 
      Netherlands Cancer Institute, Amsterdam, The Netherlands.
FAU - van Trommel, Nienke
AU  - van Trommel N
AUID- ORCID: 0000-0003-3656-947X
AD  - Department of Gynecologic Oncology, Netherlands Cancer Institute, Antoni Van 
      Leeuwenhoek, Amsterdam, The Netherlands.
FAU - Beerendonk, Ina
AU  - Beerendonk I
AUID- ORCID: 0000-0003-3179-3763
AD  - Department of Obstetrics and Gynecology, Radboud University Medical Center, 
      Nijmegen, The Netherlands.
FAU - Amant, Frederic
AU  - Amant F
AUID- ORCID: 0000-0002-5452-4905
AD  - Department of Gynecologic Oncology, Netherlands Cancer Institute, Antoni Van 
      Leeuwenhoek, Amsterdam, The Netherlands.
AD  - Department of Gynecologic Oncology, UZ Leuven, Leuven, Belgium.
FAU - Lok, Christianne
AU  - Lok C
AUID- ORCID: 0000-0001-8693-7299
AD  - Department of Gynecologic Oncology, Netherlands Cancer Institute, Antoni Van 
      Leeuwenhoek, Amsterdam, The Netherlands. c.lok@nki.nl.
LA  - eng
PT  - Journal Article
DEP - 20220927
PL  - Germany
TA  - Arch Gynecol Obstet
JT  - Archives of gynecology and obstetrics
JID - 8710213
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - Q20Q21Q62J (Cisplatin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Pregnancy
MH  - Mice
MH  - Female
MH  - Animals
MH  - *Ovary
MH  - *Ovarian Follicle
MH  - Cyclophosphamide/adverse effects/metabolism
MH  - Cisplatin/adverse effects
MH  - Paclitaxel/adverse effects
OTO - NOTNLM
OT  - Cancer in pregnancy
OT  - Chemotherapy
OT  - Fertility
OT  - Ovarian follicles
EDAT- 2022/09/28 06:00
MHDA- 2023/03/22 06:00
CRDT- 2022/09/27 11:56
PHST- 2022/05/22 00:00 [received]
PHST- 2022/09/09 00:00 [accepted]
PHST- 2022/09/28 06:00 [pubmed]
PHST- 2023/03/22 06:00 [medline]
PHST- 2022/09/27 11:56 [entrez]
AID - 10.1007/s00404-022-06793-w [pii]
AID - 10.1007/s00404-022-06793-w [doi]
PST - ppublish
SO  - Arch Gynecol Obstet. 2023 Apr;307(4):1163-1176. doi: 10.1007/s00404-022-06793-w. 
      Epub 2022 Sep 27.