Iodine is an essential micronutrient that is required for thyroid hormone (TH) synthesis. However, adequate maternal thyroid function is critical for fetal growth and neurodevelopment. Pregnancy increases iodine requirements due to enhanced renal clearance, higher maternal TH production, and transplacental transfer, making pregnant women especially vulnerable to iodine deficiency. In this review, we examine the molecular mechanisms of TH synthesis and regulation, placental transport and metabolism, and the physiological adaptations of thyroid function during gestation. We also analyze the clinical and public health consequences of iodine imbalances, ranging from deficiency to excess. Evidence indicates that mild iodine deficiency—which is common even in developed countries—can lead to maternal thyroid overstimulation, increased thyroglobulin levels, altered T3/T4 ratios, and enlarged thyroid volume, while severe deficiency results in maternal and fetal hypothyroidism with irreversible neurocognitive impairment in the offspring. Conversely, excessive iodine intake may impair fetal thyroid function through mechanisms such as the Wolff–Chaikoff effect. In conclusion, ensuring balanced iodine intake through iodized salt, supplementation, and routine thyroid monitoring during pregnancy is essential to protect maternal health and optimize early neurodevelopment.

: In brief: The endocrine and immunological disruption induced by hyperthyroidism could alter gestation, placenta, and fetal development. This study suggests an immunological role of thyroid hormones in gestation. Thyroid dysfunctions lead to metabolic, angiogenic, and developmental alterations at the maternal–fetal interface that cause reproductive complications. Thyroid hormones (THs) act through their nuclear receptors that interact with other steroid hormone receptors. Currently, immunological regulation by thyroid status has been characterized to a far less extent. It is well known that THs exert regulatory function on immune cells and modulate cytokine expression, but how hyperthyroidism (hyper) modulates placental immunological aspects leading to placental alterations is unknown. This work aims to throw light on how hyper modulates immunological and morphological placental aspects. Control and hyper (induced by a daily s.c. injection of T4 0.25 mg/kg) Wistar rats were mated 8 days after starting T4 treatment and euthanized on days 19 (G19) and 20 (G20) of pregnancy. We removed the placenta to perform qPCR, flow cytometry, immunohistochemistry, Western blot and histological analysis, and amniotic fluid and serum to evaluate hormone levels. We observed that hyper increases the fetal number, fetal weight, and placental weight on G19. Moreover, hyper induced an endocrine imbalance with higher serum corticosterone and changed placental morphology, specifically the basal zone and decidua. These changes were accompanied by an increased mRNA expression of glucocorticoid receptor and monocyte chemoattractant protein-1, an increased mRNA and protein expression of prolactin receptor, and an increase in CD45+ infiltration. Finally, by in vitro assays, we evidenced that TH induced immune cell activation. In summary, we demonstrated that hyper modulates immunological and morphological placental aspects and induces fetal phenotypic changes, which could be related to preterm labor observed in hyper.

Iodine is a crucial component of thyroid hormones (THs), specifically triiodothyronine (T3) and thyroxine (T4) and is vital for normal thyroid function. During pregnancy, a deficiency in iodine can result in inadequate production of THs, leading to hypothyroidism. This con-dition can negatively impact the intellectual development of the newborn. Numerous stud-ies have demonstrated that iodine deficiency during pregnancy correlates with lower IQ levels in children. This deficiency can hinder critical processes such as neurogenesis, neu-ronal migration, and myelination, all of which are essential for proper cognitive develop-ment. Research indicates that children born to iodine-deficient mothers are at a higher risk of having lower IQs compared to those whose mothers received iodine supplements during pregnancy. Therefore, ensuring sufficient iodine levels and optimal TH function during pregnancy is crucial for the cognitive development of children. This highlights the im-portance of nutrition and regular monitoring of thyroid health in pregnant women. This re-view focuses on the key mechanisms of thyroid hormone homeostasis and discusses the implications of iodine deficiency during pregnancy.

Introduction: OFA hr/hr rats have deficient lactation with impaired suckling-induced PRL release. Unlike their background strain, Sprague-Dawley (SD) rats, OFA rats display abnormal mediobasal hypothalamus (MBH) dopaminergic tone during late pregnancy and lactation. We explored if the expression of MBH components, including various receptors (R) and proteins that regulate the dopaminergic system, is altered in mid-lactating OFA compared to SD rats, which may be associated with the abnormality. Methods: Four groups of mid-lactating rats were used: continuous lactation; pups separated overnight; 30-min suckling (S); and 2 h or 4 h S after separation. Mothers were sacrificed to obtain serum for PRL RIA and MBHs to determine tyrosine hydroxylase (TH), PRL-R, PRL signaling molecules (activator: STAT5b; inhibitors: SOCS1, SOCS3, CIS), opioids (PENK, PDYN), and µ- and κ-opioid R (MOR, KOR) mRNA expression by qPCR and phospho-TH (p-TH) and TH proteins by Western blot. Results: Suckling-induced PRL was lower in OFA and p-TH expression diminished in both strains. Separation increased TH mRNA and protein in SD, which decreased after 4 h S, but OFA protein levels remained unchanged. Separation of pups also resulted in decreased PRL-R and CIS expression in SD but increased PRL-R and SOCS3 in OFA. Despite the lower PRL-R, STAT5b, SOCS1, and SOCS3 levels in OFA compared to SD, suckling diminished them further. We observed subtle changes in SD opioids and their R, but in OFA, suckling decreased PENK, KOR, and MOR. Conclusion: The different patterns of TH, opioids, their R, and PRL signaling inhibitor expression with conserved TH activation by suckling may disturb the balance between stimulation and inhibition of PRL release resulting in impaired suckling-induced PRL secretion in OFA rats.

Hypoprolactinemia (hypoPRL) disrupts lactation and compromises milk production. Although maternal milk is a critical source of nutrients and bioactive compounds for newborns, the consequences of deficient lactation based on reduced milk quantity on the offspring’s immune development remain incompletely understood. Therefore, this study aimed to elucidate how deficient lactation due to hypoPRL interferes with offspring immunity and development. Female Sprague Dawley (SD) and spontaneous hypoPRL Oncins France Colony A (OFA) rats were euthanized on day 2 of lactation to assess the impact of hypoPRL on serum, milk, and tissue samples. We demonstrated that early deficient lactation in the OFA model impaired maternal performance, leading to increased pup mortality during early lactation. OFA pups exhibited reduced body weight and weight gain, decreased cerebral weight and index, and an increased cephalization index. Thymic development was markedly altered, as evidenced by reduced thymus weight, area, and cortical extension. These structural changes were accompanied by increased thymic Rag 1 expression, suggesting altered lymphocyte development. In parallel, passive immune transfer was compromised, with reduced levels of OVA-specific immunoglobulin isotypes detected in pup serum, reflecting changes in milk-derived immune support. In summary, maternal hypoPRL during early lactation adversely affects offspring growth and thymic maturation with lasting consequences for neonatal immune maturation. This study provides a novel experimental framework to investigate the consequences of lactation deficiency with potential implications for understanding lactation insufficiency and its impact on neonatal immune exposure.

Desmogleins (Dsg) are transmembrane proteins involved in cell-cell junctions. Keratinized epithelia, such as skin, express several forms of Dsg. Dsg4 deficiency is associated with hair loss in humans, mice, and rats. Recently, we reported that topical administration of imiquimod (IMQ) to Dsg4-deficient rats exacerbates skin inflammation. Different immune-mediated diseases, including Psoriasis, Spondyloarthritis, Systemic Lupus Erythematosus, and Atopic Dermatitis, involve skin inflammation. Unfortunately, the role of Dsg4 in the induction of humoral immunity has not been addressed. Our work aimed to determine whether Dsg4 deficiency impairs the induction of an antigen-specific immune response. For this purpose, Dsg4 deficient Oncins France Colony A hairless/hairless (OFA) and wild-type Sprague-Dawley (SD) rats were treated with IMQ, or vaseline, to evaluate lymph node (LN) expansion. We found that OFA rats exhibited higher LN size with histological differences compared to SD rats. Brachial LN expansion after topical IMQ treatment was reduced in OFA rats compared to SD. Surprisingly, when we evaluated the induction of the immune response to intradermal ovoalbumin (OVA) challenge, we observed that OFA rats showed lower levels of OVA-specific IgM, IgG, IgG2a and IgA than the SD group. Although further investigations are necessary, our results suggest a novel role for Dsg4 in supporting humoral immunity under inflammatory conditions.