This review summarizes our current understanding of the implication of catalase polymorphisms in the occurrence, control and comorbidities of metabolic diseases. Whatever impaired glucose tolerance, insulin resistance on diabetes and whatever their occurrence or implications, the studies taken together converge toward the hypothesis that catalase polymorphisms play a role in glucose disorders. -262C/T and -844A>G single nucleotide polymorphisms are associated to hypertension susceptibility and/or onset. Concerning dyslipidemia, very recent studies requiring confirmation report a -262C/T implication. Finally, a role of catalase polymorphisms in bone metabolism is described. Plethora of studies on catalase SNPs and their link with diseases exist. It is now clear that genetic variations in the catalase gene and its promoter are putative risk factors for metabolic disease. The question of how these polymorphisms actively play a role in various metabolisms remains unanswered. Further functional studies are required in order to gain a deeper insight into the direct role of catalase.

The glucose-regulated protein 78 (GRP78) is a molecular chaperone that is responsible for protein folding, which belongs to the heat shock protein 70 kDa (HSPA/HSP70). Because of the conjunction of GRP78 transcription with endoplasmic reticulum stress, the chaperone plays an important role in the unfolded protein response (UPR), which is induced after the accumulation of misfolded proteins. In the last years, a significant body of research concentrated on interplay between GRP78 and sexual steroid hormones. Throughout this review, we describe the mechanisms by which GRP78 regulates steroidogenesis at multiple levels and how steroids modulate GRP78 expression in different mammalian reproductive organs. Finally, we discuss the cooperation between GRP78 and steroids for cell survival and proliferation in the context of reproduction and tumorigenesis. This new paradigm offers significant opportunities for future exploration.

It is now well established that maternal serum markers are often abnormal in fetal trisomy 21. Their determination is recommended for prenatal screening and pregnancy follow-up. However, mechanisms leading to abnormal maternal serum levels of such markers are still debated. Our objective was to help clinicians and scientists unravel the pathophysiology of these markers via a review of the main studies published in this field, both in vivo and in vitro, focusing on the six most widely used markers (hCG, its free subunit hCGβ, PAPP-A, AFP, uE3, and inhibin A) as well as cell-free feto–placental DNA. Analysis of the literature shows that mechanisms underlying each marker’s regulation are multiple and not necessarily directly linked with the supernumerary chromosome 21. The crucial involvement of the placenta is also highlighted, which could be defective in one or several of its functions (turnover and apoptosis, endocrine production, and feto–maternal exchanges and transfer). These defects were neither constant nor specific for trisomy 21, and might be more or less pronounced, reflecting a high variability in placental immaturity and alteration. This explains why maternal serum markers can lack both specificity and sensitivity, and are thus restricted to screening.

Protease Inhibitors (PI e.g., ritonavir (RTV) and lopinavir (LPV)) used to treat pregnant mothers infected by HIV induce prematurity and endocrine dysfunctions. The maintenance of pregnancy relies on placental hormone production (human Chorionic Gonadotrophin (hCG) and progesterone (P4)). Those functions are ensured by the villous trophoblast and are mainly regulated by the Unfolded Protein Response (UPR) pathway and mitochondria. We investigated, in vitro, if PI impair hCG and P4 production and the potential intracellular mechanisms involved. Term villous cytotrophoblast (VCT) were cultured with or without RTV or LPV from 6 to 48 h. VCT differentiation into syncytiotrophoblast (ST) was followed measuring hCG and P4 secretion. We evaluated the expression of P4 synthesis partners (Metastatic Lymph Node 64 (MLN64), cholesterol side-chain cleavage (P450SCC), Hydroxy-delta-5-Steroid Dehydrogenase and 3 Beta-and steroid delta-isomerase 1 (HSD3B1)), of mitochondrial pro-fusion factors (Mitofusin 2 (Mfn2), Optic Atrophy 1 (OPA1)) and of UPR factors (Glucose-Regulated Protein 78 (GRP78), Activating Transcription Factor 4 (ATF4), Activating Transcription Factor 6 (ATF6), spliced X-box Binding Protein 1 (sXBP1)). RTV had no significant effect on hCG and P4 secretion, whereas lopinavir significantly decreased both secretions. LPV also decreased P450SCC and HSD3B1 expression, whereas it increased Mfn2, GRP78 and sXBP1 expression in ST. RTV has no effect on the endocrine placenta. LPV impairs both villous trophoblast differentiation and P4 production. It is likely to act via mitochondrial fusion and UPR pathway activation. These trophoblastic alterations may end in decreased P4 levels in maternal circulation, inducing prematurity.