Peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) belong to the transcription factor family, and they are highly expressed in all types of trophoblast during pregnancy. The present review discusses currently published papers that are related to the regulation of PPARs via lipid metabolism, glucose metabolism, and amino acid metabolism to affect trophoblast physiological conditions, including differentiation, maturation, secretion, fusion, proliferation, migration, and invasion. Recent pieces of evidence have proven that the dysfunctions of PPARs in trophoblast lead to several related pregnancy diseases such as recurrent miscarriage, preeclampsia, intrauterine growth restriction, and gestational diabetes mellitus. Moreover, the underlying mechanisms of PPARs in the control of these processes have been discussed as well. Finally, this review’s purposes are to provide more knowledge about the role of PPARs in normal and disturbed pregnancy with trophoblast, so as to find PPAR ligands as a potential therapeutic target in the treatment and prevention of adverse pregnancy outcomes.

In vitro maturation (IVM) of oocytes is a promising assisted reproductive technology (ART) deemed as a simple and safe procedure. It is mainly used in patients with impaired oocyte maturation and in fertility preservation for women facing the risk of losing fertility. However, to date, it is still not widely used in clinical practice because of its underperformance. The influencing factors, such as biphasic IVM system, culture medium, and the supplementation, have a marked effect on the outcomes of oocyte IVM. However, the role of different culture media, supplements, and follicular priming regimens in oocyte IVM have yet to be fully clarified and deserve further investigation.

Assisted reproductive technology (ART) has rapidly developed and is now widely practised worldwide. Both the characteristics of ART (handling gametes/embryos in vitro) and the infertility backgrounds of ART parents (such as infertility diseases and unfavourable lifestyles or diets) could cause increased oxidative stress (OS) that may exert adverse influences on gametogenesis, fertilisation, and foetation, even causing a long-lasting influence on the offspring. For these reasons, the safety of ART needs to be closely examined. In this review, from an ART safety standpoint, the origins of OS are reviewed, and the long-lasting cardiovascular effects and potential mechanisms of OS on the offspring are discussed.

Implantation consists of a complex process based on coordinated crosstalk between the endometrium and trophoblast. Furthermore, it is known that the microenvironment of this fetal–maternal interface plays an important role in the development of extravillous trophoblast cells. This is mainly due to the fact that tissues mediate embryonic signaling biologicals, among other molecules, prostaglandins. Prostaglandins influence tissue through several cell processes including differentiation, proliferation, and promotion of maternal immune tolerance. The aim of this study is to investigate the potential pathological mechanism of the prostaglandin E2 receptor 4 (EP4) in modulating extravillous trophoblast cells (EVTs) in unexplained recurrent marriage (uRM). Our results indicated that the expression of EP4 in EVTs was decreased in women experiencing uRM. Furthermore, silencing of EP4 showed an inhibition of the proliferation and induced apoptosis in vitro. In addition, our results demonstrated reductions in β- human chorionic gonadotropin (hCG), progesterone, and interleukin (IL)-6, which is likely a result from the activation of the cyclic adenosine monophosphate (cAMP)- cAMP-dependent protein kinase A (PKA)-phosphorylating CREB (pCREB) pathway. Our data might provide insight into the mechanisms of EP4 linked to trophoblast function. These findings help build a more comprehensive understanding of the effects of EP4 on the trophoblast at the fetal–maternal interface in the first trimester of pregnancy.

Epigenetics play a vital role in early embryo development. Offspring conceived via assisted reproductive technologies (ARTs) have a three times higher risk of epigenetic diseases than naturally conceived children. However, investigations into ART-associated placental histone modifications or sex-stratified analyses of ART-associated histone modifications remain limited. In the current study, we carried out immunohistochemistry, chip-sequence analysis, and a series of in vitro experiments. Our results demonstrated that placentas from intra-cytoplasmic sperm injection (ICSI), but not in vitro fertilization (IVF), showed global tri-methylated-histone-H3-lysine-4 (H3K4me3) alteration compared to those from natural conception. However, for acetylated-histone-H3-lysine-9 (H3K9ac) and acetylated-histone-H3-lysine-27 (H3K27ac), no significant differences between groups could be found. Further, sex -stratified analysis found that, compared with the same-gender newborn cord blood mononuclear cell (CBMC) from natural conceptions, CBMC from ICSI-boys presented more genes with differentially enriched H3K4me3 (n = 198) than those from ICSI-girls (n = 79), IVF-girls (n = 5), and IVF-boys (n = 2). We also found that varying oxygen conditions, RNA polymerase II subunit A (Polr2A), and lysine demethylase 5A (KDM5A) regulated H3K4me3. These findings revealed a difference between IVF and ICSI and a difference between boys and girls in H3K4me3 modification, providing greater insight into ART-associated epigenetic alteration.

Aging is the main cause of decline in oocyte quality, which can further trigger the failure of assisted reproductive technology (ART). Exploring age-related genes in oocytes is an important way to investigate the molecular mechanisms involved in oocyte aging. To provide novel insight into this field, we performed a pooled analysis of publicly available datasets, using the overlapping results of two statistical methods on two Gene Expression Omnibus (GEO) datasets. The methods utilized in the current study mainly include Spearman rank correlation, the Wilcoxon signed-rank test, t-tests, Venn diagrams, Gene Ontology (GO), Protein–Protein Interaction (PPI), Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and receiver operating characteristic (ROC) curve analysis. We identified hundreds of age-related genes across different gene expression datasets of in vitro maturation-metaphase II (IVM-MII) oocytes. Age-related genes in IVM-MII oocytes were involved in the biological processes of cellular metabolism, DNA replication, and histone modifications. Among these age-related genes, FAM111A expression presented a robust correlation with age, seen in the results of different statistical methods and different datasets. FAM111A is associated with the processes of chromosome segregation and cell cycle regulation. Thus, this enzyme is potentially an interesting novel marker for the aging of oocytes, and warrants further mechanistic study.