PMID- 31344684
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
DP  - 2019 Jul 1
TI  - Prenatal ethanol exposure induces susceptibility to premature ovarian 
      insufficiency.
LID - JOE-19-0063.R1 [pii]
LID - 10.1530/JOE-19-0063 [doi]
AB  - Prenatal ethanol exposure (PEE) adversely affects the offspring reproductive 
      system. We aimed to confirm the susceptibility to premature ovarian insufficiency 
      (POI) in female PEE offspring and elucidate its intrauterine programming 
      mechanism. The pregnant Wistar female rats were intragastrically administered 
      with 4 g/kgxd of ethanol from gestational day (GD) 9 to 20. Offspring 
      reproductive parameters were detected on GD20, postnatal week (PW) 6, and PW12. 
      The PEE foetuses showed a decreased number of oocytes, increased ovarian cell 
      apoptosis, and upregulated expression levels of ovarian insulin-like growth 
      factor 1 (IGF1) signaling pathway and steroidogenic enzymes. The proportion of 
      atretic follicles in adult rats was increased, while the number of anti-Mullerian 
      hormone-positive antral follicles was decreased. The serum oestradiol (E2) levels 
      were decreased, but the follicle stimulation hormone levels were elevated. The 
      ovarian Igf1 signaling pathway was transformed from activation during puberty to 
      relative inhibition in adulthood, and the expression levels of ovarian 
      steroidogenic enzymes were inhibited in adulthood. Furthermore, we treated the 
      human granulosa cell line KGN with different ethanol concentrations (15, 30, 60, 
      120 mM) and found that the expression of IGF1 signaling pathway components, 
      3beta-HSD, and P450arom, as well as the production of E2, was increased. After IGF1 
      siRNA transfection, P450arom expression and E2 production were downregulated. 
      These results suggest that PEE induces POI susceptibility in adult females, which 
      may be caused by over-activation of the foetal ovarian Igf1 signaling pathway and 
      steroidogenesis under PEE, resulting in accelerated early development of 
      folliculogenesis and depletion of primordial follicles.
FAU - Ni, Yuan
AU  - Ni Y
AD  - Y Ni, Reproductive Medicine Center, Wuhan University Renmin Hospital, Wuhan, 
      China.
FAU - Xu, Dan
AU  - Xu D
AD  - D Xu, Department of Pharmacology, Wuhan University, Wuhan, China.
FAU - Lv, Feng
AU  - Lv F
AD  - F Lv, Department of Pharmacology, Wuhan University, Wuhan, China.
FAU - Wan, Yang
AU  - Wan Y
AD  - Y Wan, Department of Pharmacology, Wuhan University, Wuhan, China.
FAU - Fan, Guanlan
AU  - Fan G
AD  - G Fan, Department of Pharmacology, Wuhan University, Wuhan, China.
FAU - Zou, Wen
AU  - Zou W
AD  - W Zou, Reproductive Medicine Center, Wuhan University Renmin Hospital, Wuhan, 
      China.
FAU - Chen, Yunxi
AU  - Chen Y
AD  - Y Chen, Reproductive Medicine Center, Wuhan University Renmin Hospital, Wuhan, 
      China.
FAU - Pei, Lin-Guo
AU  - Pei LG
AD  - L Pei, Department of Pharmacology, Wuhan University, Wuhan, China.
FAU - Yang, Jing
AU  - Yang J
AD  - J Yang, Reproductive Medicine Center, Wuhan University Renmin Hospital, Wuhan, 
      China.
FAU - Wang, Hui
AU  - Wang H
AD  - H Wang, Department of Pharmacology, Wuhan University, Wuhan, China.
LA  - eng
PT  - Journal Article
DEP - 20190701
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
SB  - IM
EDAT- 2019/07/26 06:00
MHDA- 2019/07/26 06:00
CRDT- 2019/07/26 06:00
PHST- 2019/02/11 00:00 [received]
PHST- 2019/07/25 00:00 [accepted]
PHST- 2019/07/26 06:00 [entrez]
PHST- 2019/07/26 06:00 [pubmed]
PHST- 2019/07/26 06:00 [medline]
AID - JOE-19-0063.R1 [pii]
AID - 10.1530/JOE-19-0063 [doi]
PST - aheadofprint
SO  - J Endocrinol. 2019 Jul 1:JOE-19-0063.R1. doi: 10.1530/JOE-19-0063.