The Ross Laboratory for Studies in Neural Birth Defects, Department of Medical Neurobiology, Institute for Medical Research - Israel-Canada and The Hebrew University-Hadassah Medical School, Box 12272, 91120, Jerusalem, Israel.
Adelson School of Medicine, Ariel University, Israel; Laboratory of Teratology, department of Medical Neurobiology, Institute for Medical Research - Israel-Canada and The Hebrew University-Hadassah Medical School, Box 12272, 91120 Jerusalem, Israel.
Brain Res Bull. 2021 Sep;174:103-121. doi: 10.1016/j.brainresbull.2021.05.026. Epub 2021 Jun 2.
Prenatal insult exposure effects on the offspring, have and are still considered the main interest of most teratological studies, while paternal and maternal preconception effects have received relatively little interest. Once thought to be a myth, paternal exposure to insults leading to numerous detrimental effects in the offspring, has been confirmed on several occasions and is gaining increased attention. These effects could be demonstrated molecularly, biochemically and/or behaviorally. Different epigenetic mechanisms have been proposed for these effects to occur, including DNA methylation, histone modification and sperm RNA transmission. Paternal insult exposure has been shown to cause several neurobehavioral and developmental defects in the offspring. Findings on parental insult exposure effects on the progeny will be discussed in this review, with the main focus being on neurobehavioral effects after parental preconceptional exposure. The exposure to the insults induced long-lasting, mostly marked, defects. A few pioneering, prevention and reversal studies were published. Interestingly, most studies were conducted on paternal exposure and, at the present state of this field, on animal models. Clinical translation remains the subsequent challenge.
产前暴露于不利因素对后代的影响，一直以来都是大多数致畸学研究的主要关注点，而父代和母代孕前暴露的影响则相对较少受到关注。尽管曾经被认为是一个神话，但父代接触不利因素会导致后代出现许多有害影响，这一点已经在多次研究中得到证实，并引起了越来越多的关注。这些影响可以在分子、生化和/或行为水平上得到证明。已经提出了不同的表观遗传机制来解释这些影响的发生，包括 DNA 甲基化、组蛋白修饰和精子 RNA 传递。父代暴露于不利因素已被证明会导致后代出现多种神经行为和发育缺陷。本文将讨论父代暴露于不利因素对后代的影响，主要关注父代孕前暴露后的神经行为效应。这些不利因素的暴露会导致持久的、大多是明显的缺陷。已经发表了一些开创性的、预防和逆转研究。有趣的是，大多数研究都是针对父代暴露进行的，而且就该领域的现状而言，这些研究都是基于动物模型进行的。临床转化仍然是后续的挑战。
