It is known that in experimental animals, metabolic disorders begin at the specific times denominated as "windows of development", which include intrauterine life and the lactation period (Sullivan and Grove, 2000; Illum et al., 2018). During these windows of development, changes in food intake result in obesity that is detected principally in adulthood and is associated with several types of comorbidities such as type 2 diabetes (T2D), insulin resistance, atherosclerosis, dyslipidemia, cardiopathies, psychiatric disorders, and certain types of cancer (Engin, 2017, Harder et al., 1999, Guilloteau et al., 2009).

The obesity induced in the pups during the pregnancy period occurs in response to the mother's increased energy intake and may be imprinted at the genomic level of the pups, which is called genomic imprinting (Harder et al., 1999, Plagemann et al., 2010, Carone et al., 2010, Radford et al., 2014; Schellong et al., 2019; Malafaia et al., 2013; Fullston et al., 2013; Cesaretti, Junior, 2006, 2015; Borengasser et al., 2013; Kufandová et al., 2014; Schoonejans and Ozanne, 2021; Ng et al., 2010).

Genomic imprinting is governed by epigenetic mechanisms, which are a collection of changes in gene expression that can be incorporated into the genome of somatic cells. However, when epigenetic changes occur in germ cells during intrauterine development, the genomic imprint can be passed on to the next generation (Slomko et al., 2012; Herrera, Lindgren, 2010, 2017).

Despite this, there are few reports showing the effect of genomic imprinting over generations in the obesity model using mother food manipulation (de Castro et al., 2015), and in a nongenetic prediabetes male rodent model (Wei et al., 2013; Li et al., 2019).

On the other hand, the lactation phase is a developmental window in which the manipulation of the mother and pups’ food may also induce the obesity condition that is observed in adulthood (Levin, 2006) For example, when there is a reduction in the number of rats (nine to three pups per litter) immediately after birth the milk supply increases, and this is a well-documented model of obesity induction during the lactation phase (Mozeš et al., 2015; Bei et al., 2015).

In contrast to genomic imprinting, this mechanism is known as metabolic imprinting, and the consequences of obesity produced in the litter size reduction model are well described only in adulthood (Sullivan and Grove, 2000; Levin, 2006; Guilloteau et al., 2009; Efková et al., 2011; Mozeš et al., 2015; de Oliveria et al., 2021). However, if obesity metabolic imprinting, which may be originated from epigenetic mechanisms and therefore be incorporated into the genes during reproduction, is herdable from one to the next generation, it remains to be determined ( Stegemann and Buchner, 2015; King and Skinner, 2020).

On the other hand, the literature has considered the study of mandible shape as a phenotype biomarker to determine the epigenetic processes and morphological variations produced during the evolution process, (Iaeger et al., 2021, Dubied et al., 2021) as well as to improve the knowledge about the genetic traits locus during the biological development of the regions of the rodents' mandible (Workman et al., 2002; Swiderski et al., 2013; Klingenberg et al., 2003, 2014; Burgio et al., 2012; Navarro, Maga, 2016).

In addition, the hemimandible shape has been used to study the effects of different experimental conditions during the mandible's growth, as for example, those related to food consistence (Renaud et al., 2012), diet (Anderson et al., 2014, Atchley et al., 1984) or hormone effects (Kesterke et al., 2018).

In this context, the effects of obesity on human mandible shape are still poorly understood (Sadeghianrizi et al., 2005), and they are completely absent in animal obesity models at the lactation windows of development. Thus, we hypothesized that metabolic imprinting and inbreeding could be heritable and change the rat's hemimandibular shape, dentine, and enamel dimensions over generations.

Therefore, we aimed to investigate the effect of obesity on enamel and dentine thickness and hemimandibular shape over generations using inbreeding and reduced numbers of rats per litter.