Transgenerational effects of prenatal exposure to the 1944-45 Dutch famine

Abstract This study was performed to examine the transgenerational effects of bisphenol (BP) A analogs, BPE, and BPS on male reproductive functions using mice as a model. CD-1 mice (F0) were orally exposed to control treatment (corn oil), BPA, BPE, or BPS (0.5 or 50 µg/kg/day) from gestational day 7 (the presence of vaginal plug = 1) to birth. Mice from F1 and F2 offspring were used to generate F3 males. Prenatal exposure to BPA, BPE, and BPS decreased sperm counts and/or motility and disrupted the progression of germ cell development as morphometric analyses exhibited an abnormal distribution of the stages of spermatogenesis in F3 males. Dysregulated serum levels of estradiol-17β and testosterone, as well as expression of steroidogenic enzymes in F3 adult testis were also observed. In the neonatal testis, although apoptosis and DNA damage were not affected, mRNA levels of DNA methyltransferases, histone methyltransferases, and their associated factors were increased by BP exposure. Furthermore, BP exposure induced immunoreactive expression of DNMT3A in Sertoli cells, strengthened DNMT3B, and weakened H3K9me2 and H3K9me3 in germ cells of the neonatal testis, whereas DNMT1, H3K4me3, and H3K27ac were not affected. In adult testis, stage-specific DNMT3B was altered by BP exposure, although DNMT3A, H3K9me2, and H3K9me3 expression remained stable. These results suggest that prenatal exposure to BPA, BPE, and BPS induces transgenerational effects on male reproductive functions probably due to altered epigenetic modification following disruption of DNMTs and histone marks in the neonatal and/or adult testis.

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Prenatal Exposure to Di(2-Ethylhexyl) Phthalate Causes Long-Term Transgenerational Effects on Female Reproduction in Mice

Endocrinology ◽

10.1210/en.2017-03004 ◽

2017 ◽

Vol 159 (2) ◽

pp. 795-809 ◽

Cited By ~ 39

Author(s):

Emily Brehm ◽

Saniya Rattan ◽

Liying Gao ◽

Jodi A Flaws

Keyword(s):

Prenatal Exposure ◽

Female Reproduction ◽

Transgenerational Effects ◽

Ethylhexyl Phthalate

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Spatiotemporal Small Non-coding RNAs Expressed in the Germline as an Early Biomarker of Testicular Toxicity and Transgenerational Effects Caused by Prenatal Exposure to Nanosized Particles

Frontiers in Toxicology ◽

10.3389/ftox.2021.691070 ◽

2021 ◽

Vol 3 ◽

Author(s):

Satoshi Yokota ◽

Ken Takeda ◽

Shigeru Oshio

Keyword(s):

Prenatal Exposure ◽

Germ Cells ◽

Small Rnas ◽

Maternal Exposure ◽

Male Reproduction ◽

Reproductive Capacity ◽

Transgenerational Effects ◽

Male Germ Cells ◽

Increased Risk ◽

Non Coding Rnas

In recent years, an apparent decline in human sperm quality has been observed worldwide. One in every 5.5 couples suffers from infertility, with male reproductive problems contributing to nearly 40% of all infertility cases. Although the reasons for the increasing number of infertility cases are largely unknown, both genetic and environmental factors can be contributing factors. In particular, exposure to chemical substances during mammalian male germ cell development has been linked to an increased risk of infertility in later life owing to defective sperm production, reproductive tract obstruction, inflammation, and sexual disorders. Prenatal exposure to nanomaterials (NMs) is no exception. In animal experiments, maternal exposure to NMs has been reported to affect the reproductive health of male offspring. Male germ cells require multiple epigenetic reprogramming events during their lifespan to acquire reproductive capacity. Given that spermatozoa deliver the paternal genome to oocytes upon fertilization, we hypothesized that maternal exposure to NMs negatively affects male germ cells by altering epigenetic regulation, which may in turn affect embryo development. Small non-coding RNAs (including microRNAs, PIWI-interacting RNAs, tRNA-derived small RNAs, and rRNA-derived small RNAs), which are differentially expressed in mammalian male germ cells in a spatiotemporal manner, could play important regulatory roles in spermatogenesis and embryogenesis. Thus, the evaluation of RNAs responsible for sperm fertility is of great interest in reproductive toxicology and medicine. However, whether the effect of maternal exposure to NMs on spermatogenesis in the offspring (intergenerational effects) really triggers multigenerational effects remains unclear, and infertility biomarkers for evaluating paternal inheritance have not been identified to date. In this review, existing lines of evidence on the effects of prenatal exposure to NMs on male reproduction are summarized. A working hypothesis of the transgenerational effects of sperm-derived epigenomic changes in the F1 generation is presented, in that such maternal exposure could affect early embryonic development followed by deficits in neurodevelopment and male reproduction in the F2 generation.

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Transgenerational effects of prenatal exposure to the Dutch famine

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/j.1471-0528.2009.02110.x ◽

2009 ◽

Vol 116 (6) ◽

pp. 868-868 ◽

Cited By ~ 13

Author(s):

LH Lumey ◽

AD Stein

Keyword(s):

Prenatal Exposure ◽

Transgenerational Effects

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Prenatal Exposure to Bisphenol A, E, and S Induces Transgenerational Effects on Female Reproductive Functions in Mice

Toxicological Sciences ◽

10.1093/toxsci/kfz124 ◽

2019 ◽

Vol 170 (2) ◽

pp. 320-329 ◽

Cited By ~ 5

Author(s):

Mingxin Shi ◽

Allison E Whorton ◽

Nikola Sekulovski ◽

James A MacLean ◽

Kanako Hayashi

Keyword(s):

Prenatal Exposure ◽

Corn Oil ◽

Follicular Development ◽

Control Treatment ◽

Serum Estradiol ◽

Transgenerational Effects ◽

Vaginal Plug ◽

Estrous Cyclicity ◽

Estradiol 17Β ◽

Bpa Analogs

Abstract This study was performed to examine the transgenerational effects of bisphenol (BP) A analogs, BPE, and BPS on female reproductive functions using mice as a model. CD-1 mice (F0) were orally exposed to control treatment (corn oil), BPA, BPE, or BPS (0.5 or 50 µg/kg/day) from gestational day 7 (the presence of vaginal plug = 1) to birth. Mice from F1 and F2 offspring were used to generate F3 females. Prenatal exposure to BPA, BPE, and BPS accelerated the onset of puberty and exhibited abnormal estrous cyclicity in F3 females, and those females exhibited mating difficulties starting at 6 months of age. Various fertility problems including reduced pregnancy rates, parturition, and nursing issues were also observed starting at 6 months, which worsened at 9 months. The levels of serum estradiol-17β were elevated by BPA or BPS exposure at the age of 6 months, whereas testosterone levels were not affected. The dysregulated expression of steroidogenic enzymes was observed in the ovary at 3 or 6 months of age by BPE or BPS exposure. However, BPA, BPE, and BPS exposure did not affect neonatal follicular development such as germ cell nest breakdown or follicle numbers in the ovary on postnatal day 4. These results suggest that prenatal exposure to BPA analogs, BPE and BPS, have transgenerational effects on female reproductive functions in mice.

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Transgenerational effects of prenatal exposure to the Dutch famine

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/j.1471-0528.2009.02108.x ◽

2009 ◽

Vol 116 (6) ◽

pp. 868-868

Author(s):

R Painter ◽

S de Rooij ◽

C Osmond ◽

P Gluckman ◽

M Hanson ◽

...

Keyword(s):

Prenatal Exposure ◽

Transgenerational Effects

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Reversal of cardiomyopathy resulting from prenatal exposure to ethanol

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100113469 ◽

1984 ◽

Vol 42 ◽

pp. 716-717

Author(s):

C. Uphoff ◽

C. Nyquist-Battie

Keyword(s):

Prenatal Exposure ◽

Heart Development ◽

Membrane Integrity ◽

Ethanol Exposure ◽

Prenatal Ethanol Exposure ◽

Pathological Changes ◽

Prenatally Exposed ◽

Inner Mitochondrial Membrane ◽

Fetal Alcohol ◽

Newborn Mice

Fetal Alcohol Syndrone (FAS) is a syndrome with characteristic abnormalities resulting from prenatal exposure to ethanol. In many children with FAS syndrome gross pathological changes in the heart are seen with septal defects the most prevalent abnormality recorded. Few studies in animal models have been performed on the effects of ethanol on heart development. In our laboratory, it has been observed that prenatal ethanol exposure of Swiss albino mice results in abnormal cardiac muscle ultrastructure when mice were examined at birth and compared to pairfed and normal controls. Fig. 1 is an example of the changes that are seen in the ethanol-exposed animals. These changes include enlarged mitochondria with loss of inner mitochondrial membrane integrity and loss of myofibrils. Morphometric analysis substantiated the presence of these alterations from normal cardiac ultrastructure. The present work was undertaken to determine if the pathological changes seen in the newborn mice prenatally exposed to ethanol could be reversed with age and abstinence.

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