Article ; Online: Timing of exposure to gonadotropins has differential effects on the conceptus: evidence from a mouse model†.
2020 Volume 103, Issue 4, Page(s) 854–865
Abstract: Superovulation with gonadotropins alters the hormonal milieu during early embryo development and placentation, and may be responsible for fetal and placental changes observed after in vitro fertilization (IVF). We hypothesized that superovulation has ... ...
| Abstract | Superovulation with gonadotropins alters the hormonal milieu during early embryo development and placentation, and may be responsible for fetal and placental changes observed after in vitro fertilization (IVF). We hypothesized that superovulation has differential effects depending on timing of exposure. To test our hypothesis, we isolated the effect of superovulation on pre- and peri-implantation mouse embryos. Blastocysts were obtained from either natural mating or following superovulation and mating, and were transferred into naturally mated or superovulated pseudopregnant recipient mice. Fetal weight was significantly lower after peri-implantation exposure to superovulation, regardless of preimplantation exposure (p = 0.006). Placentas derived from blastocysts exposed to superovulation pre- and peri-implantation were larger than placentas derived from natural blastocysts that are transferred into a natural or superovulated environment (p < 0.05). Fetal-to-placental weight ratio decreased following superovulation during the pre- or peri-implantation period (p = 0.05, 0.01, respectively) and these effects were additive. Peg3 DNA methylation levels were decreased in placentas derived from exposure to superovulation both pre- and peri-implantation compared with unexposed embryos and exposure of the preimplantation embryo only. Through RNA sequencing on placental tissue, changes were identified in genes involved in immune system regulation, specifically interferon signaling, which has been previously implicated in implantation and maintenance of early pregnancy in mice. Overall, we found that the timing of exposure to gonadotropin stimulation can have differential effects on fetal and placental growth. These findings could impact clinical practice and underscores the importance of dissecting the role of procedures utilized during IVF on pregnancy complications. |
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| MeSH term(s) | Animals ; Chorionic Gonadotropin/pharmacology ; DNA Methylation ; Drug Administration Schedule ; Embryo Transfer ; Female ; Fetal Weight ; Fetus/drug effects ; Gonadotropins, Equine/pharmacology ; Litter Size ; Male ; Mice ; Mice, Transgenic ; Organ Size ; Placenta/anatomy & histology ; Placenta/drug effects ; Pregnancy ; Pregnancy Rate ; Sex Ratio ; Superovulation/drug effects ; Tissue and Organ Harvesting |
| Chemical Substances | Chorionic Gonadotropin ; Gonadotropins, Equine |
| Language | English |
| Publishing date | 2020-06-19 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1118-6 |
| ISSN | 1529-7268 ; 0006-3363 |
| ISSN (online) | 1529-7268 |
| ISSN | 0006-3363 |
| DOI | 10.1093/biolre/ioaa109 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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