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Endocrine–Immune Crosstalk in Human Reproductive Health and Pathology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 1687

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Faculty of Medicine, National University of Cuyo, Mendoza, Argentina
Interests: systemic lupus erythematosus; autoimmunity; therapy; treatment; biomarker
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Special Issue Information

Dear Colleagues,

This Special Issue will focus on the intricate relationship between thyroid hormones, glucocorticoids, and the immune system in reproductive biology. The delicate orchestration of endocrine and immune signals plays a pivotal role in the regulation of reproductive function across sexes and species. This Special Issue aims to highlight emerging research at the intersection of thyroid hormones, glucocorticoids, and immune system dynamics within the context of reproductive health and disease, lactation, gender perspective, autoimmunity, and endocrinopathies. Thyroid hormones and glucocorticoids influence reproductive tissue, gonadal, and lactation development by integrating embryogenesis, growth, and stress responses with immunoregulation. The immune system, in turn, actively participates in processes such as implantation, placentation, and fetal tolerance. The crosstalk among these systems is increasingly recognized as critical for successful reproduction, yet the molecular mechanisms governing their interplay remain underexplored. We invite contributions that deepen our understanding of these relationships, from molecular pathways and animal models to translational studies addressing infertility, pregnancy complications, lactation, and developmental/gestational programming. By bringing together interdisciplinary perspectives, this issue seeks to advance both fundamental knowledge and clinical insights into endocrine–immune–reproductive integration.

This Special Issue aims to consolidate cutting-edge research elucidating the molecular and systemic crosstalk among thyroid hormone signaling, hypothalamic–pituitary–adrenal (HPA) axis-derived glucocorticoids, and innate and adaptive immune pathways in reproductive physiology and pathology. THs orchestrate key events including folliculogenesis, spermatogenesis, gamete competence, and early embryonic development via the modulation of gene expression, mitochondrial biogenesis, and epigenetic remodeling. Concurrently, glucocorticoids influence reproductive outcomes by mediating stress-adaptive responses and fine-tuning cytokine milieu, leukocyte trafficking, and immune tolerance mechanisms essential for embryo implantation and placental development. Dysregulation in these hormonal axes and immune modulators underlies a spectrum of reproductive disorders, such as recurrent pregnancy loss, endometriosis, and subfertility. Contributions that integrate transcriptomic, proteomic, and metabolomic approaches, utilize in vitro organoid and in vivo models, and explore translational implications in human reproductive medicine are strongly encouraged. Through this interdisciplinary lens, the issue aims to delineate key molecular targets and mechanistic pathways that govern endocrine–immune–reproductive axis homeostasis.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Sex steroids (estrogens, progesterone, and androgens) on T and B cell biology
  • Stress response and glucocorticoids
  • Prolactin, growth hormones, and glucocorticoids on thymic development
  • Thyroid hormones on T and B cell biology
  • Immunity during lactation, gestation, and neonatal development
  • Endocrine modulation of immune cells during autoimmunity and immune-mediated diseases

Dr. Juan Pablo Mackern-Oberti
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • T cells
  • B cells
  • autoimmune disease
  • reproduction
  • immunemodulation
  • inflammation
  • endocrinology
  • lactation

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Published Papers (2 papers)

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Research

15 pages, 2375 KB  
Article
Early Deficient Lactation Differentially Affects Neonatal Thymic Cortical Development and Humoral Immune Responses in Rats
by María Belén Sánchez, María Cecilia Michel Lara, María José Germanó, Flavia Judith Neira, Luciana Belén Viruel, Jacqueline Lisset Tomsich, Claudio Rodríguez-Camejo, Mariana Troncoso, Elisa Olivia Pietrobon, Marta Soaje, Ana Hernández, Evelyn L. Jara, Susana Ruth Valdez and Juan Pablo Mackern-Oberti
Int. J. Mol. Sci. 2026, 27(4), 1708; https://doi.org/10.3390/ijms27041708 - 10 Feb 2026
Viewed by 413
Abstract
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 [...] Read more.
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. Full article
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27 pages, 1925 KB  
Article
Male Stress Is Associated with Ovarian and Endometrial Responses in ICSI Cycles: Is Seminal Plasma the Linchpin?
by Marina Nikolaeva, Alla Arefieva, Alina Babayan, Andrey Romanov, Nataliya Makarova, Liubov Krechetova, Elena Kalinina and Gennady Sukhikh
Int. J. Mol. Sci. 2026, 27(1), 534; https://doi.org/10.3390/ijms27010534 - 5 Jan 2026
Viewed by 891
Abstract
Evidence indicates that seminal plasma (SP) has pregnancy-favorable biological effects, but there is no definitive proof that exposure to SP increases pregnancy rates in assisted reproductive techniques. We previously showed that this discrepancy may be due to male stress altering SP composition. This [...] Read more.
Evidence indicates that seminal plasma (SP) has pregnancy-favorable biological effects, but there is no definitive proof that exposure to SP increases pregnancy rates in assisted reproductive techniques. We previously showed that this discrepancy may be due to male stress altering SP composition. This study investigated the association between male stress biomarkers in saliva, serum and SP and key determinants of female fertility in women exposed to their partner’s SP during the intracytoplasmic sperm injection (ICSI) cycle. The prospective pilot study included couples with tubal infertility who had unprotected intercourse during the ICSI cycle, supplemented by intravaginal SP injection on the oocyte retrieval day. Salivary cortisol and seminal noradrenaline were quantified by enzyme-linked immunosorbent assay to assess the activity of the hypothalamic–pituitary–adrenal axis and sympathetic nervous systems. Seminal interleukin-18 was measured using LegendPlex™ technology. Cluster analysis of male stress biomarkers identified two neuroendocrine-immune (NEI) phenotypes, characterized by signs of acute (phenotype-1) and chronic (phenotype-2) stress. Women with NEI phenotype-2 partners had fewer collected, mature, and fertilized oocytes, thinner endometrium, and significantly lower pregnancy rates (18.2%) compared to those with NEI phenotype-1 partners (84.6%). These data may suggest a dual role for SP in female fertility, depending on the type of male stress. Full article
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