Embryo transfer cannot delineate between the maternal pregnancy environment and germ line effects in the transgenerational transmission of disease in rats

Melanie Tran, Linda Gallo, Alanna Nicole Hanvey, Andrew J Jefferies, Kerryn T Westcott, Luise A Cullen-McEwen, David K Gardner, Karen M Moritz, Mary E Wlodek

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

Adverse conditions in utero can have transgenerational effects, in the absence of a subsequent insult. We aimed to investigate the contribution of the maternal pregnancy environment vs. germ line effects in mediating alterations to cardiorenal and metabolic physiology in offspring from mothers born small. Uteroplacental insufficiency was induced by bilateral uterine artery and vein ligation (Restricted group) or sham surgery (Control group) in Wistar-Kyoto rats. Restricted and control female offspring (F1) were mated with either breeder males (embryo donor) or vasectomized males (embryo recipient). Embryo transfer was performed at embryonic day (E) 1, whereby second-generation (F2) embryos gestated (donor-in-recipient) in either a control (Cont-in-Cont, Rest-in-Cont) or restricted (Cont-in-Rest, Rest-in-Rest) mother. In male and female offspring, glomerular number and size were measured at postnatal day (PN) 35, and systolic blood pressure, glucose control, insulin sensitivity, and pancreatic beta-cell mass were measured in separate sibling cohorts at 6 mo. Rest-in-Rest offspring were hypothesized to have similar characteristics (reduced growth, altered metabolic control, and hypertension) to non-embryo-transferred Rest, such that embryo transfer would not be a confounding experimental influence. However, embryo-transferred Rest-in-Rest offspring underwent accelerated growth during the peripubertal phase, followed by slowed growth between 2 and 3 mo of age compared with non-embryo-transferred Rest groups. Furthermore, renal function and insulin response to a glucose load were different to respective non-embryo-transferred groups. Our data demonstrate the long-term effects of in vitro embryo manipulation, which confounded the utility of this approach in delineating between the maternal pregnancy environment and germ line effects that drive transgenerational outcomes.
Original languageEnglish
Pages (from-to)607 - 618
Number of pages12
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume306
Issue number8
DOIs
Publication statusPublished - 2014

Cite this

Tran, Melanie ; Gallo, Linda ; Hanvey, Alanna Nicole ; Jefferies, Andrew J ; Westcott, Kerryn T ; Cullen-McEwen, Luise A ; Gardner, David K ; Moritz, Karen M ; Wlodek, Mary E. / Embryo transfer cannot delineate between the maternal pregnancy environment and germ line effects in the transgenerational transmission of disease in rats. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2014 ; Vol. 306, No. 8. pp. 607 - 618.
@article{d3958f5f72c946d78b94fa9d152d6abb,
title = "Embryo transfer cannot delineate between the maternal pregnancy environment and germ line effects in the transgenerational transmission of disease in rats",
abstract = "Adverse conditions in utero can have transgenerational effects, in the absence of a subsequent insult. We aimed to investigate the contribution of the maternal pregnancy environment vs. germ line effects in mediating alterations to cardiorenal and metabolic physiology in offspring from mothers born small. Uteroplacental insufficiency was induced by bilateral uterine artery and vein ligation (Restricted group) or sham surgery (Control group) in Wistar-Kyoto rats. Restricted and control female offspring (F1) were mated with either breeder males (embryo donor) or vasectomized males (embryo recipient). Embryo transfer was performed at embryonic day (E) 1, whereby second-generation (F2) embryos gestated (donor-in-recipient) in either a control (Cont-in-Cont, Rest-in-Cont) or restricted (Cont-in-Rest, Rest-in-Rest) mother. In male and female offspring, glomerular number and size were measured at postnatal day (PN) 35, and systolic blood pressure, glucose control, insulin sensitivity, and pancreatic beta-cell mass were measured in separate sibling cohorts at 6 mo. Rest-in-Rest offspring were hypothesized to have similar characteristics (reduced growth, altered metabolic control, and hypertension) to non-embryo-transferred Rest, such that embryo transfer would not be a confounding experimental influence. However, embryo-transferred Rest-in-Rest offspring underwent accelerated growth during the peripubertal phase, followed by slowed growth between 2 and 3 mo of age compared with non-embryo-transferred Rest groups. Furthermore, renal function and insulin response to a glucose load were different to respective non-embryo-transferred groups. Our data demonstrate the long-term effects of in vitro embryo manipulation, which confounded the utility of this approach in delineating between the maternal pregnancy environment and germ line effects that drive transgenerational outcomes.",
author = "Melanie Tran and Linda Gallo and Hanvey, {Alanna Nicole} and Jefferies, {Andrew J} and Westcott, {Kerryn T} and Cullen-McEwen, {Luise A} and Gardner, {David K} and Moritz, {Karen M} and Wlodek, {Mary E}",
year = "2014",
doi = "10.1152/ajpregu.00523.2013",
language = "English",
volume = "306",
pages = "607 -- 618",
journal = "American Journal of Physiology - Regulatory Integrative and Comparative Physiology",
issn = "1522-1490",
publisher = "American Physiological Society",
number = "8",

}

Embryo transfer cannot delineate between the maternal pregnancy environment and germ line effects in the transgenerational transmission of disease in rats. / Tran, Melanie; Gallo, Linda; Hanvey, Alanna Nicole; Jefferies, Andrew J; Westcott, Kerryn T; Cullen-McEwen, Luise A; Gardner, David K; Moritz, Karen M; Wlodek, Mary E.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 306, No. 8, 2014, p. 607 - 618.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Embryo transfer cannot delineate between the maternal pregnancy environment and germ line effects in the transgenerational transmission of disease in rats

AU - Tran, Melanie

AU - Gallo, Linda

AU - Hanvey, Alanna Nicole

AU - Jefferies, Andrew J

AU - Westcott, Kerryn T

AU - Cullen-McEwen, Luise A

AU - Gardner, David K

AU - Moritz, Karen M

AU - Wlodek, Mary E

PY - 2014

Y1 - 2014

N2 - Adverse conditions in utero can have transgenerational effects, in the absence of a subsequent insult. We aimed to investigate the contribution of the maternal pregnancy environment vs. germ line effects in mediating alterations to cardiorenal and metabolic physiology in offspring from mothers born small. Uteroplacental insufficiency was induced by bilateral uterine artery and vein ligation (Restricted group) or sham surgery (Control group) in Wistar-Kyoto rats. Restricted and control female offspring (F1) were mated with either breeder males (embryo donor) or vasectomized males (embryo recipient). Embryo transfer was performed at embryonic day (E) 1, whereby second-generation (F2) embryos gestated (donor-in-recipient) in either a control (Cont-in-Cont, Rest-in-Cont) or restricted (Cont-in-Rest, Rest-in-Rest) mother. In male and female offspring, glomerular number and size were measured at postnatal day (PN) 35, and systolic blood pressure, glucose control, insulin sensitivity, and pancreatic beta-cell mass were measured in separate sibling cohorts at 6 mo. Rest-in-Rest offspring were hypothesized to have similar characteristics (reduced growth, altered metabolic control, and hypertension) to non-embryo-transferred Rest, such that embryo transfer would not be a confounding experimental influence. However, embryo-transferred Rest-in-Rest offspring underwent accelerated growth during the peripubertal phase, followed by slowed growth between 2 and 3 mo of age compared with non-embryo-transferred Rest groups. Furthermore, renal function and insulin response to a glucose load were different to respective non-embryo-transferred groups. Our data demonstrate the long-term effects of in vitro embryo manipulation, which confounded the utility of this approach in delineating between the maternal pregnancy environment and germ line effects that drive transgenerational outcomes.

AB - Adverse conditions in utero can have transgenerational effects, in the absence of a subsequent insult. We aimed to investigate the contribution of the maternal pregnancy environment vs. germ line effects in mediating alterations to cardiorenal and metabolic physiology in offspring from mothers born small. Uteroplacental insufficiency was induced by bilateral uterine artery and vein ligation (Restricted group) or sham surgery (Control group) in Wistar-Kyoto rats. Restricted and control female offspring (F1) were mated with either breeder males (embryo donor) or vasectomized males (embryo recipient). Embryo transfer was performed at embryonic day (E) 1, whereby second-generation (F2) embryos gestated (donor-in-recipient) in either a control (Cont-in-Cont, Rest-in-Cont) or restricted (Cont-in-Rest, Rest-in-Rest) mother. In male and female offspring, glomerular number and size were measured at postnatal day (PN) 35, and systolic blood pressure, glucose control, insulin sensitivity, and pancreatic beta-cell mass were measured in separate sibling cohorts at 6 mo. Rest-in-Rest offspring were hypothesized to have similar characteristics (reduced growth, altered metabolic control, and hypertension) to non-embryo-transferred Rest, such that embryo transfer would not be a confounding experimental influence. However, embryo-transferred Rest-in-Rest offspring underwent accelerated growth during the peripubertal phase, followed by slowed growth between 2 and 3 mo of age compared with non-embryo-transferred Rest groups. Furthermore, renal function and insulin response to a glucose load were different to respective non-embryo-transferred groups. Our data demonstrate the long-term effects of in vitro embryo manipulation, which confounded the utility of this approach in delineating between the maternal pregnancy environment and germ line effects that drive transgenerational outcomes.

UR - http://ajpregu.physiology.org/content/306/8/R607.full-text.pdf+html

U2 - 10.1152/ajpregu.00523.2013

DO - 10.1152/ajpregu.00523.2013

M3 - Article

VL - 306

SP - 607

EP - 618

JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

SN - 1522-1490

IS - 8

ER -