+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Advanced maternal age causes adverse programming of mouse blastocysts leading to altered growth and impaired cardiometabolic health in post-natal life



Advanced maternal age causes adverse programming of mouse blastocysts leading to altered growth and impaired cardiometabolic health in post-natal life



Human Reproduction 31(9): 1970-1980



Does advanced maternal age (AMA) in mice affect cardiometabolic health during post-natal life in offspring derived from an assisted reproduction technology (ART) procedure? Offspring derived from blastocysts collected from aged female mice displayed impaired body weight gain, blood pressure, glucose metabolism and organ allometry during post-natal life compared with offspring derived from blastocysts from young females; since all blastocysts were transferred to normalized young mothers, this effect is independent of maternal pregnancy conditions. Although studies in mice have shown that AMA can affect body weight and behaviour of offspring derived from natural reproduction, data on the effects of AMA on offspring cardiometabolic health during post-natal development are not available. Given the increasing use of ART to alleviate infertility in women of AMA, it is pivotal to develop ART-AMA models addressing the effects of maternal aging on offspring health. Blastocysts from old (34-39 weeks) or young (8-9 weeks) C57BL/6 females mated with young CBA males (13-15 weeks) were either subjected to differential cell staining (inner cell mass and trophectoderm) or underwent embryo transfer (ET) into young MF1 surrogates (8-9 weeks) to produce young (Young-ET, 9 litters) and old (Old-ET, 10 litters) embryo-derived offspring. Offspring health monitoring was carried out for 30 weeks. All animals were fed with standard chow. Blood pressure was measured at post-natal Weeks 9, 15 and 21, and at post-natal Week 30 a glucose tolerance test (GTT) was performed. Two days after the GTT mice were killed for organ allometry. Blastocyst cell allocation variables were evaluated by T-test and developmental data were analysed with a multilevel random effects regression model. The total number of cells in blastocysts from aged mice was decreased (P < 0.05) relative to young mice due to a lower number of cells in the trophectoderm (mean ± SEM: 34.5 ± 2.1 versus 29.6 ± 1.0). Weekly body weight did not differ in male offspring, but an increase in body weight from Week 13 onwards was observed in Old-ET females (final body weight at post-natal Week 30: 38.5 ± 0.8 versus 33.4 ± 0.8 g, P < 0.05). Blood pressure was increased in Old-ET offspring at Weeks 9-15 in males (Week 9: 108.5 ± 3.13 versus 100.8 ± 1.5 mmHg, Week 15: 112.9 ± 3.2 versus 103.4 ± 2.1 mmHg) and Week 15 in females (115.9 ± 3.7 versus 102.8 ± 0.7 mmHg; all P < 0.05 versus Young-ET). The GTT results and organ allometry were not affected in male offspring. In contrast, Old-ET females displayed a greater (P < 0.05) peak glucose concentration at 30 min during the GTT (21.1 ± 0.4 versus 17.8 ± 1.16 mmol/l) and their spleen weight (88.2 ± 2.6 ± 105.1 ± 4.6 mg) and several organ:body weight ratios (g/g × 10(3)) were decreased (P < 0.05 versus Young-ET), including the heart (3.7 ± 0.06 versus 4.4 ± 0.08), lungs (4.4 ± 0.1 versus 5.0 ± 0.1), spleen (2.4 ± 0.06 versus 3.2 ± 0.1) and liver (36.4 ± 0.6 versus 39.1 ± 0.9). Results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models that can produce hypotheses for eventual testing in the target species (i.e. humans). Our data show that offspring from mouse embryos from aged mothers can develop altered phenotypes during post-natal development compared with embryos from young mothers. Because all embryos were transferred into young mothers for the duration of pregnancy to normalize the maternal in vivo environment, our findings indicate that adverse programming via AMA is already established at the blastocyst stage. Whilst human embryos display increased aneuploidy compared with mouse, we believe our data have implications for women of AMA undergoing assisted reproduction, including surrogacy programmes. This work was supported through the European Union FP7-CP-FP Epihealth programme (278418) to T.P.F. and the BBSRC (BB/F007450/1) to T.P.F. The authors have no conflicts of interest to declare.

(PDF emailed within 0-6 h: $19.90)

Accession: 057145832

Download citation: RISBibTeXText

PMID: 27402911

DOI: 10.1093/humrep/dew177


Related references

Blastocysts from advanced maternal age mice and post-natal consequences. Placenta 57: 241-242, 2017

The effect of pre natal and post natal nutrition on the growth of beef cattle 2. the effect of severe restriction in early post natal life on growth and feed efficiency during recovery. Australian Journal of Agricultural Research 31(1): 179-190, 1980

The embryonic and post natal growth of rat and mouse part 1 the embryonic and early post natal growth of the whole embryo a model with exponential growth and sudden changes in growth rate. Acta Anatomica 82(3): 305-336, 1972

The effect of pre natal and post natal nutrition on the growth of beef cattle 3. the effect of severe restriction in early post natal life on the development of the body components and chemical composition. Australian Journal of Agricultural Research 31(1): 191-204, 1980

Altered growth patterns and depressed pituitary growth hormone content in young rats effects of pre natal and post natal thio uracil administration. Growth 46(4): 296-305, 1982

Pre natal and post natal maternal components in house mouse behavior. Behavior Genetics 7(1): 58-59, 1977

The effect of pre- and post-natal nutrition on the growth of beef cattle. 2. The effect of severe restriction in early post-natal life on growth and feed efficiency during recovery. Australian Journal of Agricultural Research 31(1): 179-189, 1980

Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health. Plos One 7(12): E52791, 2013

Maternal and placental chorionic somatomammotropin levels in relation to pre natal and post natal growth. Pediatric Research 6(4): 354, 1972

Pre natal and post natal maternal influences on growth in mice selected for body weight. Genetics 64(1): 59-68, 1970

Role of the pre- and post-natal environment in developmental programming of health and productivity. Molecular and Cellular Endocrinology 354(1-2): 54-59, 2012

Pre natal and post natal influences on mouse growth. Journal Of Animal Science: 180, 1972

Embryonic and post natal growth of the rat and mouse 6. pre natal growth of organs and tissues individual organs final remarks on parts 1 6 phase transitions. Acta Anatomica 106(1): 108-128, 1980

The maternal influence upon pre natal and post natal development in pigs of extremely differing sizes growth of german improved landrace and gottingen dwarfs after reciprocal transplantation of fertilized eggs. Zeitschrift fuer Tierzuechtung und Zuechtungsbiologie 83(4): 312-330, 1967

Studies of sexual differentiation of sheep. I. Foetal and maternal modifications and post-natal plasma LH and testosterone content following androgenisation early in gestation. II. Evidence for post-natal hypothalamic hypophysiotrophic depression of basal LH secretion following pre-natal androgenisation. Acta Endocrinologica 89(1): 182-195, 1978