Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Adverse Neurodevelopmental Outcomes

Monica Mainigi, Jason M. Rosenzweig, Jun Lei, Virginia Mensah, Lauren Thomaier, C. Conover Talbot, Devvora Olalere, Teri Ord, Rayyan Rozzah, Michael V. Johnston, Irina Burd

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


While live births resulting from assisted reproductive technology (ART) exceed 1% of total births annually, the effect of ART on fetal development is not well understood. Data have demonstrated that IVF leads to alterations in DNA methylation and gene expression in the placenta that may have long-term effects on health and disease. Studies have linked adverse neurodevelopmental outcomes to ART, although human studies are inconclusive. In order to isolate the peri-implantation environment and its effects on brain development, we utilized a mouse model with and without superovulation and examined the effect of adult behavior as well as adult cortical neuronal density. Adult offspring of superovulated dams showed increased anxiety-like behavior compared to offspring of naturally mated dams (P <.05). There was no difference in memory and learning tests between the 2 groups. The adult brains from offspring of superovulated recipients had fewer neurons per field compared to naturally mated control offspring (P <.05). In order to examine potential pathways leading to these changes, we measured messenger RNA and microRNA (miRNA) expression in fetal brains at E18.5. Microarray analysis found that miRNAs miR-122, miR-144, and miR-211, involved in regulation of neuronal migration and differentiation, were downregulated in brains of offspring exposed to a superovulated environment(P <.05). There was also altered expression of genes involved in neuronal development. These results suggest that the peri-implantation environment can affect neurodevelopment and can lead to behavioral changes in adulthood. Human studies with long-term follow-up of children from ART are necessary to further investigate the influence of ART on the offspring.

Original languageEnglish (US)
Pages (from-to)785-794
Number of pages10
JournalReproductive Sciences
Issue number6
StatePublished - Jun 2016
Externally publishedYes

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Aramco Services Company Fellowship (JR), NICHD K08HD073315 (IB), Passano Foundation Grant (IB), Reproductive Scientists Development Program/NIH K12 HD000849-22 (MM), American Society for Reproductive Medicine (MM), and Society for Gynecologic Investigation.

Publisher Copyright:
© Society for Gynecologic Investigation.


  • ART
  • IVF
  • epigenetics
  • neurodevelopment
  • neuronal differentiation
  • superovulation


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