Evidence map›Paper›PMID 40036079›Full record

ArticleJCI insight2025

In vitro fertilization induces reproductive changes in male mouse offspring and has multigenerational effects.

Eric A Rhon-Calderon, Cassidy N Hemphill, Alexandra J Savage, Laren Riesche, Richard M Schultz, Marisa S Bartolomei

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. Reproductive life after in vitro fertilization.The Journal of clinical investigation · 2026
    Article
  3. Article
  4. Ultra-low oxygen tension duringbioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
4 · The record

Corrections and comments

  • Update of
    2024
5 · Who and what money

Authors and funding

6 authors.

Eric A Rhon-CalderonEpigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Cassidy N HemphillEpigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Alexandra J SavageEpigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Laren RiescheEpigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Richard M SchultzDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Marisa S BartolomeiEpigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DOUGLAS J EPSTEIN · 1986 to 2026
$48.3M
Research Project 4: Epigenetic Regulation of Retrotransposon Silencing and Male Fertility in the MouseP50HD068157 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI MARISA S. BARTOLOMEI, CHRISTOS COUTIFARIS · 2014 to 2026
$16.3M
TRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM007229 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1985 to 2023
$14.0M
PROJECT 4: TARGETING ADP-RIBOSE POLYMER DEPENDENT EPIGENETIC EVENTS IN MALE LINEU54HD068157 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 2011 to 2013
$4.8M
Assessment of reproductive outcomes on adult offspring from in vitro fertilization using a mouse modelF32HD107914 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI RHON CALDERON, ERIC ALEJANDRO · 2022 to 2024
$232k
NICHD NIH HHS F32 HD107914NICHD NIH HHS P50 HD068157NICHD NIH HHS U54 HD068157NIDDK NIH HHS P30 DK019525NIGMS NIH HHS T32 GM007229
6 · The paper itself

Abstract

In vitro fertilization (IVF) is a noncoital method of conception used to treat human infertility. Although IVF is viewed as largely safe, it is associated with adverse outcomes in the fetus, placenta, and adult offspring. Because studies focusing on the effect of IVF on the male reproductive system are limited, we used a mouse model to assess the morphological and molecular effects of IVF on male offspring. We evaluated 3 developmental stages: 18.5-day fetuses and 12- and 39-week-old adults. Regardless of age, we observed changes in testicular-to-body weight ratios, serum testosterone levels, testicular morphology, gene expression, and DNA methylation. Also, sperm showed changes in morphology and DNA methylation. To assess multigenerational phenotypes, we mated IVF-conceived and naturally conceived males with wild-type females. Offspring from IVF males exhibited decreased fetal-to-placental weight ratios and changes in placenta gene expression and morphology regardless of sex. At 12 weeks of age, offspring showed higher body weights and differences in glucose, triglyceride, insulin, total cholesterol, HDL-C, and LDL/VLDL-C levels. Both sexes showed changes in gene expression in liver, testes, and ovaries and decreased global DNA methylation. Collectively, our findings demonstrate that male IVF offspring exhibit abnormal testicular and sperm morphology and molecular alterations with a multigenerational impact.

Indexed as

Fertilization in VitroAnimalsDNA MethylationFemaleMaleMiceMice, Inbred C57BLPlacentaPregnancySpermatozoaTestisTestosteroneTestosteroneDevelopmentEpigeneticsFertilityMouse modelsReproductive biology

Identifiers

PMID40036079
PMCPMC12016927

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.