Sex and the preimplantation embryo: implications of sexual dimorphism in the preimplantation period for maternal programming of embryonic development

Abstract

The developmental program of the embryo displays a plasticity that can result in long-acting effects that extend into post-natal life. In mammals, adult phenotype can be altered by changes in the maternal environment during the preimplantation period. One characteristic of developmental programming during this time is that the change in adult phenotype is often different for female offspring than for male offspring. In this paper, we propose the hypothesis that sexual dimorphism in preimplantation programming is mediated, at least in part, by sex-specific responses of embryos to maternal regulatory molecules whose secretion is dependent on maternal environment. The strongest evidence for this idea comes from the study of colony-stimulating factor 2 (CSF2). Expression of CSF2 from the oviduct and endometrium is modified by environmental factors of the mother, in particular seminal plasma and obesity. Additionally, CSF2 alters several properties of the preimplantation embryo and has been shown to alleviate negative consequences of culture of mouse embryos on postnatal phenotype in a sex-dependent manner. In cattle, exposure of preimplantation bovine embryos to CSF2 causes sex-specific changes in gene expression, interferon-τ secretion, and DNA methylation later in pregnancy (day 15 of gestation). It is likely that several embryokines can alter postnatal phenotype through actions directed towards the preimplantation embryo. Identification of these molecules and elucidation of the mechanisms by which sexually-disparate programming is established will lead to new insights into the control and manipulation of embryonic development.

Sex Differences in Early Embryogenesis: Inter‐Chromosomal Regulation Sets the Stage for Sex‐Biased Gene Networks

“…[72] In fact, many diseases with early developmental origins display sex biases. In the same vein, the sex of the embryo can be considered an additional "environmental" or programming factor in the establishment of the epigenome.…”

“…In the same vein, the sex of the embryo can be considered an additional "environmental" or programming factor in the establishment of the epigenome. [41,72] Also, there are evocative reports of sex-specific signaling by the embryo to the mother. [73,74] Studies in rodent, bovine, and human blastocysts have shown that the response to environmental conditions is different in male and female embryos, [75,76] reflecting differences in their metabolism.…”

“…[72] For example, maternal diet produces effects that differ between males and females. [72] For example, maternal diet produces effects that differ between males and females.…”

Developmental sexual dimorphism and the evolution of mechanisms for adjustment of sex ratios in mammals

“…For example, glucose does not always inhibit preimplantation development, indicating that the response is variable . Furthermore, there is not only sexually dimorphic gene expression preimplantation but also considerable variation in that gene expression between individual embryos, and the sex‐specific responses are influenced by maternal regulatory factors that vary with the maternal environment . Together, these studies suggest that there is variation in responsiveness and potential for maternal control, suggesting avenues for future research.…”

Reproductive systems biology tackles global issues of population growth, food safety and reproductive health

“…Similarly, livestock embryos conceived by artificial insemination (AI) or produced in vitro and transferred to recipients are prone to early embryonic death resulting in early pregnancy losses that lower AI conception rates down to 35-45 % and account for millions of lost dollars in the beef and dairy cattle industries (Hansen et al 2004). In this regard, P. Hansen et al discuss the sex-specific expression of colony stimulating factor CSF2 (Loureiro et al 2009) and related mechanisms guiding preimplantation embryo programming, which leads to the establishment and sustenance of pregnancy, a developmental milestone that is equally important for the management of human and animal reproductive health (Hansen et al 2015). Among possible causes of preimplantation embryo changes that may lead to developmental arrest and epigenetic abnormalities, the endoplasmatic reticulum stress (Hao et al 2009), caused by exogenous factors during laboratory procedures necessary for human/animal embryo production, is discussed by Latham (2015).…”