Changes in sex ratio from fertilization to birth in assisted-reproductive-treatment cycles

Tarı́n, Juan J.; Garcı́a-Pérez, Miguel A.; Hermenegildo, Carlos; Cano, Antonio

doi:10.1186/1477-7827-12-56

Cited by 55 publications

(49 citation statements)

References 66 publications

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“…In other animal-based maternal dietary models focused on the periconceptional period, gender-specific cardiometabolic or growth phenotype differences have been observed in offspring (Sinclair et al 2007;Bermejo-Alvarez et al 2011). Similarly, in assisted reproductive technology (ART)-related embryo environment models, sexual dimorphism in embryo survival and adult offspring phenotype has been recorded (Fernández-Gonzalez et al 2004;Sjöblom et al 2005;Feuer et al 2014;Tarín et al 2014). Why might this occur following dietary challenge at the preimplantation stage?…”

Section: Discussionmentioning

confidence: 99%

“…Differing environmental sensitivities by male and female embryos before gonadal development and direct sex hormone effects can be influential most likely derive from sex chromosome dosage effects on transcriptional activity (Bermejo-Alvarez et al 2011). Downstream from transcriptional differences, gender-specific variance in metabolism and growth rates may emerge in response to environmental challenge (Erickson 1997;Bermejo-Alvarez et al 2011), and this may be substantiated by X-inactivation in females (Tarín et al 2014) and by sex hormone effects during subsequent fetal development. The emergence and propagation of sexual dimorphic responses to dietary challenge from the preimplantation period onwards will be one important direction for future research.…”

Section: Discussionmentioning

confidence: 99%

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Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo’s potential, affecting adult health

Fleming

Watkins

Sun

et al. 2015

Reprod. Fertil. Dev.

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Periconceptional environment may influence embryo development, ultimately affecting adult health. Here, we review the rodent model of maternal low-protein diet specifically during the preimplantation period (Emb-LPD) with normal nutrition during subsequent gestation and postnatally. This model, studied mainly in the mouse, leads to cardiovascular, metabolic and behavioural disease in adult offspring, with females more susceptible. We evaluate the sequence of events from diet administration that may lead to adult disease. Emb-LPD changes maternal serum and/or uterine fluid metabolite composition, notably with reduced insulin and branched-chain amino acids. This is sensed by blastocysts through reduced mammalian target of rapamycin complex 1 signalling. Embryos respond by permanently changing the pattern of development of their extra-embryonic lineages, trophectoderm and primitive endoderm, to enhance maternal nutrient retrieval during subsequent gestation. These compensatory changes include stimulation in proliferation, endocytosis and cellular motility, and epigenetic mechanisms underlying them are being identified. Collectively, these responses act to protect fetal growth and likely contribute to offspring competitive fitness. However, the resulting growth adversely affects long-term health because perinatal weight positively correlates with adult disease risk. We argue that periconception environmental responses reflect developmental plasticity and 'decisions' made by embryos to optimise their own development, but with lasting consequences.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo’s potential, affecting adult health

Fleming

Watkins

Sun

et al. 2015

Reprod. Fertil. Dev.

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show abstract

“…In the study by Orzack et al (2015), ART included both IVF and ICSI, and the sex ratio was determined for the combined IVF-and ISCI-produced embryos. In most previous studies, the sex ratios of IVF-or ICSI-produced embryos/offspring were analyzed separately, and IVF was shown to result in a male-biased sex ratio (Avery et al 1991, Gutierrez-Adan et al 2001, Wrenzycki et al 2002, Dean et al 2010, Maalouf et al 2014, Torner et al 2014, while ICSI resulted in a female-biased sex ratio (Bu et al 2014, Maalouf et al 2014, Tarin et al 2014. Therefore, ICSI and IVF may affect sex ratios via different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

IVF affects embryonic development in a sex-biased manner in mice

Tan¹,

Wang²,

Zhang³

et al. 2016

Reproduction

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Increasing evidence indicates that IVF (IVF includes in vitro fertilization and culture) embryos and babies are associated with a series of health complications, and some of them show sex-dimorphic patterns. Therefore, we hypothesized that IVF procedures have sex-biased or even sex-specific effects on embryonic and fetal development. Here, we demonstrate that IVF-induced side effects show significant sexual dimorphic patterns from the pre-implantation to the prenatal stage. During the pre-implantation stage, female IVF embryos appear to be more vulnerable to IVF-induced effects, including an increased percentage of apoptosis (7.22G1.94 vs 0.71G0.76, P!0.01), and dysregulated expression of representative sex-dimorphic genes (Xist, Hprt, Pgk1 and Hsp70). During the mid-gestation stage, IVF males had a higher survival rate than IVF females at E13.5 (male:femaleZ1.33:1), accompanied with a female-biased pregnancy loss. In addition, while both IVF males and females had reduced placental vasculogenesis/angiogenesis, the compensatory placental overgrowth was more evident in IVF males. During the late-gestation period, IVF fetuses had a higher sex ratio (male:femaleZ1.48:1) at E19.5, and both male and female IVF placentas showed overgrowth. After birth, IVF males grew faster than their in vivo (IVO) counterparts, while IVF females showed a similar growth pattern with IVO females. The present study provides a new insight into understanding IVF-induced health complications during embryonic and fetal development. By understanding and minimizing these sex-biased effects of the IVF process, the health of IVF-conceived babies may be improved in the future.

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“…Several studies reporting long-term consequences of in vitro culture or other ART identified a sex bias in the frequency and nature of the long-term effect (FernandezGonzalez et al 2004, Sjoblom et al 2005, Feuer & Rinaudo 2012, Tarin et al 2014. These deleterious effects have pointed to epigenetic alterations produced by ARTs.…”

Section: Sex-specific Long-term Effects Mediated By Assisted Reproducmentioning

confidence: 99%

Early sex-dependent differences in response to environmental stress

et al. 2018

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Developmental plasticity enables the appearance of long-term effects in offspring caused by exposure to environmental stressors during embryonic and foetal life. These long-term effects can be traced to pre-and post-implantation development, and in both cases, the effects are usually sex specific. During preimplantation development, male and female embryos exhibit an extensive transcriptional dimorphism mainly driven by incomplete X chromosome inactivation. These early developmental stages are crucial for the establishment of epigenetic marks that will be conserved throughout development, making it a particularly susceptible period for the appearance of long-term epigenetic-based phenotypes. Later in development, gonadal formation generates hormonal differences between the sexes, and male and female placentae exhibit different responses to environmental stressors. The maternal environment, including hormones and environmental insults during pregnancy, contributes to sex-specific placental development that controls genetic and epigenetic programming during foetal development, regulating sex-specific differences, including sex-specific epigenetic responses to environmental hazards, leading to long-term effects. This review summarizes several human and animal studies examining sex-specific responses to environmental stressors during both the periconception period (caused by differences in sex chromosome dosage) and placental development (caused by both sex chromosomes and hormones). The identification of relevant sex-dependent trajectories caused by sex chromosomes and/or sex hormones is essential to define diagnostic markers and prevention/intervention protocols.Reproduction (2018) 155 R39-R51

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Changes in sex ratio from fertilization to birth in assisted-reproductive-treatment cycles

Cited by 55 publications

References 66 publications

Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo’s potential, affecting adult health

Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo’s potential, affecting adult health

IVF affects embryonic development in a sex-biased manner in mice

Early sex-dependent differences in response to environmental stress

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