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Overweight\/obesity increases the risk of infertility, and of the pregnant mother and her child for developing metabolic conditions. Overweight\/obesity has been recreated in mice, but most studies focus on the effects of chronic, long\u2010term HFHS diet exposure. Here, we exposed mice to HFHS from 3\u2009weeks prior to pregnancy with the aim of determining impacts on fertility, and gestational and neonatal outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Time\u2010domain NMR scanning was used to assess adiposity, glucose, and insulin tolerance tests were employed to examine metabolic physiology, and morphological and proteomic analyses conducted to assess structure and nutrient levels of maternal organs and placenta.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fertility measures of HFHS dams were largely the same as controls. HFHS dams had increased adiposity pre\u2010pregnancy, however, exhibited exacerbated lipolysis\/hyper\u2010mobilization of adipose stores in late pregnancy. While there were no differences in glucose or insulin tolerance, HFHS dams were hyperglycemic and hyperinsulinemic in pregnancy. HFHS dams had fatty livers and altered pancreatic islet morphology. Although fetuses were hyperglycemic and hyperinsulinemic, there was no change in fetal growth in HFHS dams. There were also reductions in placenta formation. Moreover, there was increased offspring loss during lactation, which was related to aberrant mammary gland development and milk protein composition in HFHS dams.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings are relevant given current dietary habits and the development of maternal and offspring alterations in the absence of an increase in maternal weight and adiposity during pregnancy, which are the current clinical markers to determine risk across gestation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13861","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T07:44:23Z","timestamp":1658821463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Obesogenic diet in mice compromises maternal metabolic physiology and lactation ability leading to reductions in neonatal viability"],"prefix":"10.1111","volume":"236","author":[{"given":"Samantha C.","family":"Lean","sequence":"first","affiliation":[{"name":"Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro A.","family":"Candia","sequence":"additional","affiliation":[{"name":"Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience University of Cambridge  Cambridge UK"},{"name":"Department for the Woman and Newborn Health Promotion Universidad de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edina","family":"Gulacsi","sequence":"additional","affiliation":[{"name":"Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle C. 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