title: Molecular basis of thyrotropin and thyroid hormone action during implantation and early development.
abstract: BACKGROUND
  Implantation and early embryo development are finely regulated processes in which several molecules are involved. Evidence that thyroid hormones (TH: T4 and T3) might be part of this machinery is emerging. An increased demand for TH occurs during gestation, and any alteration in maternal thyroid physiology has significant implications for both maternal and fetal health. Not only overt but also subclinical hypothyroidism is associated with infertility as well as with obstetric complications, including disruptions and disorders of pregnancy, labor, delivery, and troubles in early neonatal life.
  
  
  METHODS
  We searched the PubMed and Google Scholar databases for articles related to TH action on ovary, endometrium, trophoblast maturation and embryo implantation. In addition, articles on the regulation of TH activity at cellular level have been reviewed. The findings are hereby summarized and critically discussed.
  
  
  RESULTS
  TH have been shown to influence endometrial, ovarian and placental physiology. TH receptors (TR) and thyrotropin (thyroid-stimulating hormone: TSH) receptors (TSHR) are widely expressed in the feto-maternal unit during implantation, and both the endometrium and the trophoblast might be influenced by TH either directly or through TH effects on the synthesis and activity of implantation-mediating molecules. Interestingly, due to the multiplicity of mechanisms involved in TH action (e.g. differential expression of TR isoforms, heterodimeric receptor partners, interacting cellular proteins, and regulating enzymes), the TH concentration in blood is not always predictive of their cellular availability and activity at both genomic and nongenomic level.
  
  
  CONCLUSIONS
  In addition to the known role of TH on the hormonal milieu of the ovarian follicle cycle, which is essential for a woman's fertility, evidence is emerging on the importance of TH signaling during implantation and early pregnancy. Based on recent observations, a local action of TH on female reproductive organs and the embryo during implantation appears to be crucial for a successful pregnancy. Furthermore, an imbalance in the spatio-temporal expression of factors involved in TH activity might induce early arrest of pregnancy in women considered as euthyroid, based on their hormonal blood concentration. In conclusion, alterations of the highly regulated local activity of TH may play a crucial, previously underestimated, role in early pregnancy and pregnancy loss. Further studies elucidating this topic should be encouraged.
authors.affiliation: Department of Systems' Medicine, University of Rome Tor Vergata, UOC of Endocrinology and Diabetes, Section of Reproductive Endocrinology Fatebenefratelli Hospital, 'Isola Tiberina' 00187, Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Colicchia
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier1, 00133 Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Campagnolo
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Enke
authors.initials: E
authors.lastname: Baldini
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ulisse
authors.affiliation: Department of Obstetrics and Gynaecology, University of Rome Tor Vergata, Fatebenefratelli Hospital 'Isola Tiberina', 00187 Rome, Italy.
authors.forename: Herbert
authors.initials: H
authors.lastname: Valensise
authors.affiliation: Department of Systems' Medicine, University of Rome Tor Vergata, UOC of Endocrinology and Diabetes, Section of Reproductive Endocrinology Fatebenefratelli Hospital, 'Isola Tiberina' 00187, Rome, Italy moretti@med.uniroma2.it.
authors.forename: Costanzo
authors.initials: C
authors.lastname: Moretti
mesh_terms: D000022:Abortion, Spontaneous / Q000503:physiopathology; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D007037:Hypothyroidism / Q000503:physiopathology; D010062:Ovulation Induction; D010929:Placentation / Q000502:physiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology; D013963:Thyroid Hormones / Q000097:blood / Q000502:physiology*; D013972:Thyrotropin / Q000502:physiology*; D014327:Trophoblasts / Q000502:physiology
chemical_list: D013963:Thyroid Hormones; D013972:Thyrotropin
keywords: implantation window; pregnancy; thyroid hormones; thyrotropin; trophoblast