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. 2025 Mar 22;15(7):917.
doi: 10.3390/ani15070917.

Modulation of the Toll-like Receptor Pathway in Ovine Endometria During Early Pregnancy

Guoao Yu  1 , Mengyao Song  1 , Chenxu Wu  1 , Xiaoxin Ma  1 , Leying Zhang  1 , Ling Yang  1
Affiliations

Modulation of the Toll-like Receptor Pathway in Ovine Endometria During Early Pregnancy

Guoao Yu et al. Animals (Basel). .

Abstract

Correct immunological dialogue between the maternal uterus and conceptus is essential during implantation, and Toll-like receptors (TLRs) participate in maternal immune tolerance during pregnancy. This study aimed to analyze the effect of early pregnancy on Toll-like receptor pathways in the ovine endometrium. Ovine endometria were obtained on day 16 of the estrous cycle (N16) and days 13, 16, and 25 of pregnancy (P13, P16, and P25), and expression profiles of TLR members, including TLRs, tumor necrosis factor receptor-associated factor 6 (TRAF6), interleukin 1 receptor-associated kinase 1 (IRAK1), and myeloid differentiation primary response gene 88 (MyD88), were detected by quantitative real-time PCR, Western blot analysis, and immunohistochemistry analysis. The data of this study showed that the expression of TLR2 and TLR5 was gradually increased during early pregnancy compared to N16, and TLR3 expression was greater at P16 and P25 than at N16 and P13. However, the expression levels of TLR4 and TRAF6 were weaker at P13 and P16, and the expression of MyD88 was inhibited by early pregnancy. Furthermore, early pregnancy regulated IRAK1 expression. These findings corroborated that the TLR pathway was modulated in the ovine endometrium during early pregnancy, which may be involved in maternal immunoregulation.

Keywords: endometrium; pregnancy; sheep; toll-like receptor.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Relative expression values of (A) TLR2, (B) TLR3, (C) TLR4, (D) TLR5, (E) IRAK1, (F) TRAF6, and (G) MYD88 mRNA in the endometrium. Significant differences (p < 0.05) are indicated by different letters (a, b, c, and d).
Figure 2
Figure 2
Expression of TLR2, TLR3, TLR4, TLR5, IRAK1, TRAF6, and MyD88 proteins in the endometrium. Significant differences (p < 0.05) are indicated by different letters (a, b, c, and d).
Figure 3
Figure 3
Representative immunohistochemical localization of TLR4 and MyD88 proteins in the ovine endometrium. The TLR4 protein was mainly located in the superficial glandular epithelium (sGE) and glandular epithelium (GE), and the MyD88 protein was mainly limited to the stroma (S), with weak signals in sGE and GE. HE = stained by hematoxylin and eosin; LE = luminal epithelium; NC = negative control; N16 = day 16 of the estrous cycle; P13 = day 13 of pregnancy; P16 = day 16 of pregnancy; P25 = day 25 of pregnancy. Bar = 20 µm.
Figure 4
Figure 4
Sketch of TLR signaling pathways in maternal endometrium during early pregnancy. Green, stimulators; pink, negative regulators; gray, changed.
See this image and copyright information in PMC

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