Sex-Selective Increase of IGF-2 Expression in the Hypoxic Guinea Pig Placenta of Growth-Restricted Fetuses.

Autor: Elsamadicy EA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Thompson LP; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. lthompson1@umm.edu.
Jazyk: angličtina
Zdroj: Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2022 Oct; Vol. 29 (10), pp. 3015-3025. Date of Electronic Publication: 2022 May 26.
DOI: 10.1007/s43032-022-00979-y
Abstrakt: Chronic hypoxia can cause fetal growth restriction (FGR) through placental dysfunction. Insulin-like growth factors (IGFs), such as IGF-2, play a major role in preservation of placental growth and function. We investigated the effects of chronic hypoxia and sex on protein expression of the IGF-2 pathway in placentas selected from asymmetric-FGR fetuses. Time-mated pregnant guinea pigs were assigned to normoxia (NMX, 21% O 2 ) or hypoxia (HPX, 10.5% O 2 ) during the last 14 days of pregnancy. Placentas were selected from male and female symmetrically grown NMX fetuses (fetal wt between 25th ile-75th ile) and HPX fetuses of asymmetric-FGR (fetal wt < 25th ile and brain:liver wt > 50th ile). Effects of HPX and sex on placenta protein expression of the IGF-2 signaling proteins (IGF-2, PI3K, AKT-P, total AKT, PCNA, a cell proliferation marker) were evaluated by immunoblotting. Effects of HPX and sex on morphometric parameters were analyzed using two-way ANOVA (p < 0.05). HPX reduced (p < 0.005) fetal wt by ~ 35% compared to NMX in both sexes. Expression of IGF-2 was lower (p = 0.029) in NMX female placentas compared to males. Despite lower NMX levels, HPX increased (p < 0.05) expression of IGF-2, AKT-P, relative AKT-P, and PCNA in female placentas only and had no effect on protein expression in male placentas. The female guinea pig placenta exhibits a greater sensitivity than males to HPX in upregulating expression of the IGF-2 axis. In addition, the sex difference in baseline IGF-2 expression suggests a greater capacity for females to increase IGF-2 in response to HPX as a placental adaptation in FGR.
(© 2022. Society for Reproductive Investigation.)
Databáze: MEDLINE
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