Mouse offspring conceived by in vitro fertilization exhibit accelerated reproductive aging through premature ovarian insufficiency
Eric A. Rhon-Calderon, Cassidy N. Hemphill, Alexandra J. Savage, Ana Domingo-Muelas, Zhengfeng Liu, Christopher J. Krapp, Laren Riesche, Nicolas Plachta, Richard M. Schultz, Marisa S. Bartolomei
Eric A. Rhon-Calderon, Cassidy N. Hemphill, Alexandra J. Savage, Ana Domingo-Muelas, Zhengfeng Liu, Christopher J. Krapp, Laren Riesche, Nicolas Plachta, Richard M. Schultz, Marisa S. Bartolomei
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Research Article Development Reproductive biology

Mouse offspring conceived by in vitro fertilization exhibit accelerated reproductive aging through premature ovarian insufficiency

Abstract

Reproductive aging is characterized by a progressive decline of reproductive function, with broad implications for overall health and longevity. Environmental factors, including assisted reproductive technologies (ARTs), can accelerate reproductive aging by promoting premature ovarian insufficiency in females. In vitro fertilization (IVF), though widely used and generally considered safe, has been associated with lasting effects on offspring health. Using a mouse model that closely approximates human IVF, we demonstrated that IVF accelerated reproductive aging in female offspring by inducing premature ovarian insufficiency. IVF-conceived female mice exhibited altered ovarian function, reduced follicle reserve, disrupted endocrine profiles, and transcriptomic and epigenetic changes consistent with premature reproductive decline. These findings reveal long-term consequences of IVF on female reproductive health and highlight the need to understand how early-life interventions influence reproductive longevity.

Authors

Eric A. Rhon-Calderon, Cassidy N. Hemphill, Alexandra J. Savage, Ana Domingo-Muelas, Zhengfeng Liu, Christopher J. Krapp, Laren Riesche, Nicolas Plachta, Richard M. Schultz, Marisa S. Bartolomei

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Figure 7

Number of pups and resorption rates for IVF-conceived female offspring.

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Number of pups and resorption rates for IVF-conceived female offspring. ...
(A) Experimental design and mouse model. Top: F2 Naturally conceived offspring were generated by mating CF-1 male mice with naturally conceived CF-1 female offspring at 12 weeks of age. Bottom: F2 IVF-conceived offspring were generated by mating CF-1 male mice with IVF-derived female offspring at 12 weeks of age. The different coat colors shown in the schematic represent the mixed genetic background of the offspring. Pregnant females from both groups were analyzed at E18.5, and concepti were collected following c-section. Additional breeding pairs were allowed to deliver naturally, and litter size was recorded at P1. (B) Number of pups at E18.5, number of resorptions, and total pups born across 4 consecutive litters. Each dot represents 1 independent litter from a separate breeding pair. Data are presented as the mean ± SEM. Sample sizes: n = 5 breeding pairs/litters per group for E18.5 and resorption analyses; n = 4 consecutive litters per breeding pair for postnatal litter analyses. Statistical significance between natural and IVF groups was determined using an unpaired, 2-tailed t test. *P < 0.05, compared with Naturals.