From implantation to birth: insight into molecular melatonin functions

Melatonin is a lipophilic hormone synthesized and secreted mainly in the pineal gland, acting as a neuroendocrine transducer of photoperiodic information during the night. In addition to this activity, melatonin has shown an antioxidant function and a key role as regulator of physiological processes related to human reproduction. Melatonin is involved in the normal outcome of pregnancy, beginning with the oocyte quality, continuing with embryo implantation, and finishing with fetal development and parturition. Melatonin has been shown to act directly on several reproductive events, including folliculogenesis, oocyte maturation, and corpus luteum (CL) formation. The molecular mechanism of action has been investigated through several studies which provide solid evidence on the connections between maternal melatonin secretion and embryonic and fetal development. Melatonin administration, reducing oxidative stress and directly acting on its membrane receptors, melatonin thyroid hormone receptors (MT1 and MT2), displays effects on the earliest phases of pregnancy and during the whole gestational period. In addition, considering the reported positive effects on the outcomes of compromised pregnancies, melatonin supplementation should be considered as an important tool for supporting fetal development, opening new opportunities for the management of several reproductive and gestational pathologies

Adverse Effects of Trichothiodystrophy DNA Repair and Transcription Gene Abnormalities on Human Fetal Development

The effects of DNA repair and transcription genes in human prenatal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10^-6^) recessive disorder caused by mutations in genes involved in the nucleotide excision repair (NER) pathway and in transcription. Based on our clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD-affected offspring (N=24) with respect to abnormalities in their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (N=18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD-affected pregnancies. Gestational complications were noted in nearly all pregnancies resulting in TTD-affected offspring with _XPD_ and _TTDN1_, but not _TTD-A_, gene mutations. Abnormal placental development may explain the constellation of observed complications; therefore, we hypothesize that some TTD genes play an important role in normal placental and fetal development. We investigated this hypothesis by analyzing the expression patterns of TTD genes. Expression of _TTDA_ was strongly negatively correlated (r=-0.7,P<0.0001) with gestational age, while _XPD, XPB_ and _TTDN1_ were consistently expressed from 14 to 40 weeks gestation. *Conclusion:* Our results indicate an important role for _XPD, XPB_ and _TTDN1_ gene products during normal human placental and fetal development

Influence of relative NK-DC abundance on placentation and its relation to epigenetic programming in the offspring

Normal placentation relies on an efficient maternal adaptation to pregnancy. Within the decidua, natural killer (NK) cells and dendritic cells (DC) have a critical role in modulating angiogenesis and decidualization associated with pregnancy. However, the contribution of these immune cells to the placentation process and subsequently fetal development remains largely elusive. Using two different mouse models, we here show that optimal placentation and fetal development is sensitive to disturbances in NK cell relative abundance at the fetal–maternal interface. Depletion of NK cells during early gestation compromises the placentation process by causing alteration in placental function and structure. Embryos derived from NK-depleted dams suffer from intrauterine growth restriction (IUGR), a phenomenon that continued to be evident in the offspring on post-natal day 4. Further, we demonstrate that IUGR was accompanied by an overall reduction of global DNA methylation levels and epigenetic changes in the methylation of specific hepatic gene promoters. Thus, temporary changes within the NK cell pool during early gestation influence placental development and function, subsequently affecting hepatic gene methylation and fetal metabolism.Fil: Freitag, Nancy. Medicine University of Berlin; AlemaniaFil: Zwier, M. V.. University of Groningen; Países BajosFil: Barrientos, Gabriela Laura. Medicine University of Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tirado González, Irene. Medicine University of Berlin; AlemaniaFil: Conrad, Melanie L.. Medicine University of Berlin; AlemaniaFil: Rose, Matthias. Medicine University of Berlin; AlemaniaFil: Scherjon, S. A.. University of Groningen; Países BajosFil: Plösch, T.. University of Groningen; Países BajosFil: Blois, Sandra M.. Medicine University of Berlin; Alemani

A generalized invariant imbedding equation II

Research into fetal development and medicin

Creating a Clearinghouse to Evaluate Environmental Risks to Fetal Development

In this Article, the Author explores current challenges to accessing and evaluating information about environmental risks to fetal development. She investigates these challenges within the context of the existing regulatory framework for environmental risks. As a result of this analysis, she highlights the need for and proposes creating an independent non-profit umbrella organization—a clearinghouse—to collect, distill, interpret, and make accessible the research on environmental threats to fetal development and to apply that research to evaluating relevant U.S. policy. The Author defines broadly the research on fetal development that lies within the charge of the clearinghouse to include not only research about chemical toxicant risks but also research involving environmental risks related to criminal and social justice policies

Relationship between Vitamin and Fetal Development

胎儿在母体宫内发育经过受精卵、胚胎、胎儿三个阶段,任何影响母胎健康的病因都影响宫内受精卵、胚胎和胎儿的发育,严重者甚至导致胚胎停育、胎死宫内。缺乏维生素容易诱发人体各种疾病,孕期母体维生素的需要量增加,如果孕期母体维生素摄入不足、补充不够、未得到及时增加或增加过量,都会影响胎儿器官的正常发育,导致胎儿发育不良。有些严重的胎儿畸形是致死性的,因此孕期要注意筛查及时处理。孕期加强母胎保健,重视优生优育,改善孕妇和儿童营养状况,合理调配膳食,适当补充维生素,了解各种维生素的功效和胎儿发育的相关性,有助于降低新生儿出生缺陷、防治妇女儿童营养缺乏病。aFertilized egg, embryo and fetus are three stages of fetus growth in maternal intrauterine. Any factors caused by the mother or the fetus can affect intrauterine growth of fertilized egg, embryo and fetus. Some serious factors could lead to embryonic growth cease, even fetal death. Lack of vitamin can induce human related diseases, and vitamin requirements are increased in pregnant women. If insufficient of vitamin intake in those pregnant women, fetus could suffer from dysplasia. Some severe fetal abnormalities can cause fetal death. So, it is necessary that pregnant women should have fetal developmental screening, and that those pregnant women with vitamin insufficient should be treated in time. The reasonable supplement of vitamins, and deployment of diet, is benefit for them to reduce neonatal defects, and to prevent the nutrition-related diseases in pregnant women

Opioid Maintenance Therapy on Fetal Development

Abstract Introduction and Background: Methadone, Buprenorphine and other opioid management therapies are being put into effect to help pregnant women who have abused opioids in the months prior to getting pregnant and continued the abuse during pregnancy. Purpose Statement: The purpose of this research was to determine if opioid maintenance therapies would have lasting effects on infants in their growth development. The population in the studies were derived from women who had or were currently abusing opioids during their pregnancy. The interventions taken were to prescribe women with a specific opioid maintenance treatment and measure the outcome on the infant such as birth weight, head circumference, ability to eat, etc. Literature Review: The East Tennessee State University Sherrod Library database was used to search for articles pertaining to the research. The method includes searching for key terms such as opioids on fetal development and ways to improve fetal development with opioid addiction within the years of 2017 to 2022 from peer reviewed journal articles. Findings: The researchers in each study were able to come to a consensus that there were no more effects put into fetal development with the opioid therapy and the subjects that were not given therapy during pregnancy. Conclusion: In the end, some studies showed minor effects that infants would have with getting opioid maintenance therapy in utero but concluded that infants would not experience any more damage to their development by receiving the treatment over infants who did not receive the treatment in utero

Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube

p600 Plays Essential Roles in Fetal Development

p600 is a multifunctional protein implicated in cytoskeletal organization, integrin-mediated survival signaling, calcium-calmodulin signaling and the N-end rule pathway of ubiquitin-proteasome-mediated proteolysis. While push, the Drosophila counterpart of p600, is dispensable for development up to adult stage, the role of p600 has not been studied during mouse development. Here we generated p600 knockout mice to investigate the in vivo functions of p600. Interestingly, we found that homozygous deletion of p600 results in lethality between embryonic days 11.5 and 13.5 with severe defects in both embryo and placenta. Since p600 is required for placental development, we performed conditional disruption of p600, which deletes selectively p600 in the embryo but not in the placenta. The conditional mutant embryos survive longer than knockout embryos but ultimately die before embryonic day 14.5. The mutant embryos display severe cardiac problems characterized by ventricular septal defects and thin ventricular walls. These anomalies are associated with reduced activation of FAK and decreased expression of MEF2, which is regulated by FAK and plays a crucial role in cardiac development. Moreover, we observed pleiotropic defects in the liver and brain. In sum, our study sheds light on the essential roles of p600 in fetal development