The involvement of the Toll-like receptor family in ovulation

Liu, Zhilin; Shimada, M.; Richards, JoAnne S.

doi:10.1007/s10815-008-9219-0

Cited by 71 publications

(50 citation statements)

References 40 publications

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“…Most interesting of the 10 reproductive genes located at the very highly significantly associated QTL region on SSC14 for LN-PDR, TRAFD1 is one of the negative regulators for the Toll-like receptor signaling pathway. Although the Toll-like receptor signaling pathway is related to innate immunity, several recent studies have shown that this pathway is involved in ovulation, transport of oocytes in the oviduct and during fertilization (Mashima et al, 2005;Herath et al, 2007;Liu et al, 2008;.…”

Section: Discussionmentioning

confidence: 99%

Whole-genome association analyses for lifetime reproductive traits in the pig

Onteru

Fan

Nikkilä

et al. 2011

Journal of Animal Science

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Profits for commercial pork producers vary in part because of sow productivity or sow productive life (SPL) and replacement costs. During the last decade, culling rates of sows have increased to more than 50% in the United States. Both SPL and culling rates are influenced by genetic and nongenetic factors. A whole-genome association study was conducted for pig lifetime reproductive traits, including lifetime total number born (LTNB), lifetime number born alive (LNBA), removal parity, and the ratio between lifetime nonproductive days and herd life. The proportion of phenotypic variance explained by markers was 0.15 for LTNB and LNBA, 0.12 for removal parity, and 0.06 for the ratio between lifetime nonproductive days and herd life. Several informative QTL regions (e.g., 14 QTL regions for LTNB) and genes within the regions (e.g., SLC22A18 on SSC2 for LTNB) were associated with lifetime reproductive traits in this study. Genes associated with LTNB and LNBA were similar, reflecting the high genetic correlation (0.99 ± 0.003) between these traits. Functional annotation revealed that many genes at the associated regions are expressed in reproductive tissues. For instance, the SLC22A18 gene on SSC2 associated with LTNB has been shown to be expressed in the placenta of mice. Many of the QTL regions showing associations coincided with previously identified QTL for fat deposition. This reinforces the role of fat regulation for lifetime reproductive traits. Overall, this whole-genome association study provides a list of genomic locations and markers associated with pig lifetime reproductive traits that could be considered for SPL in future studies. ABSTRACT: Profits for commercial pork producers vary in part because of sow productivity or sow productive life (SPL) and replacement costs. During the last decade, culling rates of sows have increased to more than 50% in the United States. Both SPL and culling rates are influenced by genetic and nongenetic factors. A whole-genome association study was conducted for pig lifetime reproductive traits, including lifetime total number born (LTNB), lifetime number born alive (LNBA), removal parity, and the ratio between lifetime nonproductive days and herd life. The proportion of phenotypic variance explained by markers was 0.15 for LTNB and LNBA, 0.12 for removal parity, and 0.06 for the ratio between lifetime nonproductive days and herd life. Several informative QTL regions (e.g., 14 QTL regions for LTNB) and genes within the regions (e.g., SLC22A18 on SSC2 for LTNB) were associated with lifetime reproductive traits in this study. Genes associated with LTNB and LNBA were similar, reflecting the high genetic correlation (0.99 ± 0.003) between these traits. Functional annotation revealed that many genes at the associated regions are expressed in reproductive tissues. For instance, the SLC22A18 gene on SSC2 associated with LTNB has been shown to be expressed in the placenta of mice. Many of the QTL regions showing associations coincided with previously identified QTL for fat d...

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Section: Discussionmentioning

confidence: 99%

Whole-genome association analyses for lifetime reproductive traits in the pig

Onteru

Fan

Nikkilä

et al. 2011

Journal of Animal Science

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“…The expression of genes frequently associated with innate immune responses, many potent cytokines, such as IL-6, and runt-related transcription factor 1 (RUNX1) and RUNX2 are also impaired in mice lacking ERK1/2 (103,(115)(116)(117) (Figure 3). Recently, IL-6 alone has been shown to stimulate COC expansion and induce the expression of specific genes encoding proteins involved in this process (115).…”

Section: New Insights Into Factors Controlling Ovulation and Luteinizmentioning

confidence: 99%

The ovary: basic biology and clinical implications

Richards

Pangas²

2010

J. Clin. Invest.

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424

276

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The classical view of ovarian follicle development is that it is regulated by the hypothalamic-pituitary-ovarian axis, in which gonadotropin-releasing hormone (GnRH) controls the release of the gonadotropic hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and that ovarian steroids exert both negative and positive regulatory effects on GnRH secretion. More recent studies in mice and humans indicate that many other intra-ovarian signaling cascades affect follicular development and gonadotropin action in a stage-and context-specific manner. As we discuss here, mutant mouse models and clinical evidence indicate that some of the most powerful intraovarian regulators of follicular development include the TGF-β/SMAD, WNT/FZD/β-catenin, and RAS/ERK1/2 signaling pathways and the FOXO/FOXL2 transcription factors. IntroductionThe ovary is a highly organized composite of germ cells (oocytes or eggs) and somatic cells (granulosa cells, thecal cells, and stromal cells) whose interactions dictate formation of oocyte-containing follicles, development of both oocytes and somatic cells as follicles, ovulation, and formation of the corpus luteum (the endocrine structure that forms from the ovarian follicle after ovulation and is required for establishing and maintaining pregnancy) (Figure 1). Many events in the adult ovary are controlled by two hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), secreted from the anterior pituitary gland under the control of pulses of gonadotropin-releasing hormone (GnRH) from the hypothalamus (Figure 1). Low-frequency GnRH pulses stimulate a slight increase in FSH levels early in a woman's menstrual cycle, enhancing follicle growth, while high-frequency GnRH pulses lead to a sharp rise in levels of LH just before mid-cycle (an event known as the "LH surge"), triggering ovulation and formation of the corpus luteum (Figure 1). The ovary also has a key role in these processes, ensuring the timely release of fertilizable oocytes and the maintenance of luteal cell function, a necessity for pregnancy, by directing feedback mechanisms to the hypothalamus and pituitary. For example, estrogen produced by the cells of the developing follicle both inhibits GnRH production in the hypothalamus and elicits elevated GnRH pulses, which trigger the mid-cycle LH surge that initiates ovulation. Thus, fertility depends on highly orchestrated endocrine events involving multiple organ systems.Disruption of this finely controlled network can lead to many clinical syndromes including premature ovarian failure (POF), polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome, ovulation defects, poor oocyte quality, and cancer. The goal of this Review is to cover some of the advances in our understanding of the basic biology of the mammalian ovary that may shed light on specific ovarian dysfunctions that lead to infertility. We primarily focus on recent developments using mouse genetic models to study follicle growth and ovarian function because of the inherent di...

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“…adaptive) immune response (Medzhitov et al 1997, Takeda & Akira 2005. Moreover, multiple reports of TLRs in non-immune tissues have begun to surface, bringing to light non-immune-related functions of these PRRs (Liu et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, recent reports have implied a role for TLR signaling in the regulation of vertebrate ovarian function (Shimada et al 2006, Herath et al 2007, Subdei et al 2007, Liu et al 2008. TLRs have been identified in ovarian cells from multiple species (murine, bovine, chicken), and have been shown in bovine and murine granulosa cells to functionally mediate steroidogenesis and pathogen phagocytosis respectively (Herath et al 2007, Shimada et al 2006.…”

Section: Introductionmentioning

confidence: 99%

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Toll-like receptor signaling in hen ovarian granulosa cells is dependent on stage of follicle maturation

2009

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The recent identification of toll-like receptor (TLR) signaling within ovarian granulosa cells has broad implications for ovarian physiology. Functions of TLRs within granulosa cells of the laying hen are of particular interest due to the method of transovarian transmission of Salmonella enteritidis, which results in egg contamination. This study utilized hen granulosa cells to evaluate the expression and function of Gallus TLR-signaling at distinct stages of follicular maturity. Data presented herein demonstrate the presence of TLR2, TLR4, and TLR15 mRNAs in undifferentiated granulosa cells from prehierarchal follicles and differentiated granulosa cells from preovulatory follicles, together with mRNAs encoding adaptor proteins and signaling components required for TLR signaling gene. Treatment with lipopolysaccharide (LPS) or LH, in vitro, led to the differential regulation of TLRs based on the stage of follicle maturation, with the largest (F1) follicle granulosa cells having the most rapid response. Furthermore, treatment with LPS resulted in attenuation of agonistinduced progesterone synthesis in undifferentiated, but not differentiated, granulosa cells. Additionally, undifferentiated granulosa cells were significantly more sensitive to LPS-induced apoptosis than differentiated granulosa cells from the F1 follicle. Together, these data provide evidence for a complete and functional TLR signaling pathway in hen granulosa cells, with effects on steroidogenesis and cell viability dependent upon stage of maturation. These differences may reflect the susceptibility of granulosa cells at early stages of maturation to undergo apoptosis in response to select pathogenic stimuli, thus attenuating transovarian transmission, whereas granulosa cells from preovulatory follicles are comparably resistant to LPS-mediated apoptosis. Reproduction (2009) 137 987-996

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The involvement of the Toll-like receptor family in ovulation

Cited by 71 publications

References 40 publications

Whole-genome association analyses for lifetime reproductive traits in the pig

Whole-genome association analyses for lifetime reproductive traits in the pig

The ovary: basic biology and clinical implications

Toll-like receptor signaling in hen ovarian granulosa cells is dependent on stage of follicle maturation

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