Uterine biology in pigs and sheep

ABSTRACT: There is a dialogue between the developing conceptus (embryo-fetus and associated placental membranes) and maternal uterus which must be established during the peri-implantation period for pregnancy recognition signaling, implantation, regulation of gene expression by uterine epithelial and stromal cells, placentation and exchange of nutrients and gases. The uterus provide a microenvironment in which molecules secreted by uterine epithelia or transported into the uterine lumen represent histotroph required for growth and development of the conceptus and receptivity of the uterus to implantation. Pregnancy recognition signaling mechanisms sustain the functional lifespan of the corpora lutea (CL) which produce progesterone, the hormone of pregnancy essential for uterine functions that support implantation and placentation required for a successful outcome of pregnancy. It is within the peri-implantation period that most embryonic deaths occur due to deficiencies attributed to uterine functions or failure of the conceptus to develop appropriately, signal pregnancy recognition and/or undergo implantation and placentation. With proper placentation, the fetal fluids and fetal membranes each have unique functions to ensure hematotrophic and histotrophic nutrition in support of growth and development of the fetus. The endocrine status of the pregnant female and her nutritional status are critical for successful establishment and maintenance of pregnancy. This review addresses the complexity of key mechanisms that are characteristic of successful reproduction in sheep and pigs and gaps in knowledge that must be the subject of research in order to enhance fertility and reproductive health of livestock species.     

Select nutrients and their effects on conceptus development in mammals

The dialogue between the mammalian conceptus(embryo/fetus and associated membranes) involves signaling for pregnancy recognition and maintenance of pregnancy during the critical peri-implantation period of pregnancy when the stage is set for implantation and placentation that precedes fetal development. Uterine epithelial cells secrete and/or transport a wide range of molecules, including nutrients,collectively referred to as histotroph that are transported into the fetal-placental vascular system to support growth and development of the conceptus. The availability of uterine-derived histotroph has long-term consequences for the health and well-being of the fetus and the prevention of adult onset of metabolic diseases. Histotroph includes numerous amino acids, but arginine plays a particularly important role as a source of nitric oxide and polyamines required for fetal-placental development in rodents, swine and humans through mechanisms that remain to be fully elucidated. Mechanisms whereby arginine regulates expression of genes via the mechanistic target of rapamycin cell signaling pathways critical to conceptus development, implantation and placentation are discussed in detail in this review.     

Pregnancy recognition signaling mechanisms in ruminants and pigs

Maternal recognition of pregnancy refers to the requirement for the conceptus (embryo and its associated extra-embryonic membranes) to produce a hormone that acts on the uterus and/or corpus luteum (CL) to ensure maintenance of a functional CL for production of progesterone; the hormone required for pregnancy in most mammals. The pregnancy recognition signal in primates is chorionic gonadotrophin which acts directly on the CL via luteinizing hormone receptors to ensure maintenance of functional CL during pregnancy. In ruminants, interferon tau (IFNT) is the pregnancy recognition signal. IFNT is secreted during the peri-implantation period of pregnancy and acts on uterine epithelia to silence expression of estrogen receptor alpha and oxytocin receptor which abrogates the oxytocin-dependent release of luteolytic pulses of prostaglandin F2-alpha (PGF) by uterine epithelia; therefore, the CL continues to produce progesterone required for pregnancy. Pig conceptuses secrete interferon delta and interferon gamma during the peri-implantation period of pregnancy, but there is no evidence that they are involved in pregnancy recognition signaling. Rather, pig conceptuses secrete abundant amounts of estrogens between Days 11 to 15 of pregnancy required for maternal recognition of pregnancy. Estrogen, likely in concert with prolactin, prevents secretion of PGF into the uterine venous drainage (endocrine secretion), but maintains secretion of PGF into the uterine lumen (exocrine secretion) where it is metabolized to a form that is not luteolytic. Since PGF is sequestered within the uterine lumen and unavailable to induce luteolysis, functional CL are maintained for production of progesterone. In addition to effects of chorionic gonadotrophin, IFNT and estrogens to signal pregnancy recognition, these hormones act on uterine epithelia to enhance expression of genes critical for growth and development of the conceptus.     

Asynchronous Embryo Transfer in Sheep:Lack of Survival in Progestinized Recipient Ewes

Synchronization of development between the embryo and uterus is required for successful pregnancy establishment.Transfer of early embryos requires synchrony with the recipient uterus of 2 days or less in sheep,because asynchrony of 3 days or more results in failure of pregnancy recognition signaling for maintenance of corpus luteum (CL) and progesterone (P4) production and/or uterine support of the embryo.The objective was to determine if P4 treatment of recipient ewes would obviate the need for pregnancy recognition signaling and maintain a uterine environment conducive to embryo survival after asynchronous transfer,thereby establishing a universal recipient.Embryos (morulae/blastocysts) were recovered on day 6 from super-ovulated donor ewes.Recipient ewes received 25 mg P4 daily from day 6 post-estrus until 60 days after embryo transfer.Embryos were transferred into recipients on day 6,9,12,18,or 30 post-estrus.The pregnancy rate on day 22 post-transfer was 60% for synchronous transfers to day 6 ewes,44% and 22% for asynchronous transfers to day 9 and 12 ewes,and 0% for asynchronous transfers to day 18 and 30 ewes.On day 39 post-transfer,pregnancy rates remained 60% for day 6 ewes,33% for day 9 ewes,and 0% for day 12,18,and 30 ewes.The P4 treatment did extend the window of uterine receptivity to early embryos in ewes by one day,but did not create a universal recipient.Available results support the idea that a window of uterine receptivity to the conceptus exists in sheep that is independent of pregnancy recognition signaling.     

Equine Endometrial Gland Density and Endometrial Thickness Vary among Sampling Sites in Thoroughbred Mares

The secretions of the equine endometrial glands are essential for the survival, growth, and development of the conceptus in early pregnancy, and endometrial gland density is directly related to successful pregnancy outcome. Endometrial biopsy is routinely used to assess the reproductive potential of broodmares. Some previous studies have shown that equine endometrial glands are uniformly distributed throughout the uterus; however, other work has shown variation of the endometrial architecture between biopsy sites, suggesting that a single biopsy is not representative of the entire endometrium. The aims of this study were to assess and compare the endometrial gland density and thickness at four sampling sites in the uterus (the central segment of each uterine horn, the uterine horn-body junction, and the caudal portion of the uterine body). Endometrial samples from five nulliparous Thoroughbred mares in diestrus were obtained at necropsy and used for subsequent histomorphometric analysis. The caudal uterine body had a significantly lower endometrial gland density and endometrial thickness than the other sites. This may result in nutrient deprivation and reduced survival of embryos or fetuses in this region of the uterus. The endometrial gland density and endometrial thickness did not significantly differ between the other regions sampled, indicating that they are similarly suitable for embryonic implantation and fetal development. Our results suggest that the endometrial structure of the caudal uterine body of the mare is not representative of the endometrial morphology at other sites. Thus, the caudal uterine body is not a suitable site for routine endometrial biopsy.     

哺乳动物子宫内膜腺的发育与调控

哺乳动物的子宫内膜腺可合成和分泌或转运一些蛋白及相关物质 ,这些物质在胎儿存活、发育、妊娠识别信号的启动及胚胎着床等方面起重要的作用。子宫内膜腺的发育包括内膜上皮出芽形成内膜腺上皮、内膜腺上皮管穿过固有层及内膜腺上皮卷曲和分支等几个连续的过程。哺乳动物子宫内膜腺的形态发生受许多因素的调控 ,但确切的调控机理目前尚不完全清楚     

Trophoblastic interferon-gamma: current knowledge and possible role(s) in early pig pregnancy

In the pig as in ruminant species, the implantation of the elongated conceptus - the embryo with its associated membranes - onto the maternal uterus is accompanied by an intense secretion of interferon (IFN), which culminates at day 15 of development. It has been shown that in fact the pig trophectoderm - the polarized epithelium which lines the conceptus - simultaneously secretes two types of interferons: IFN-gamma (IFN-gamma), which is the more abundant species, is produced in very substantial amounts. Another IFN is also secreted, which happens to be a novel type I IFN, now named IFN-delta. It was previously shown that the uterus is the most probable target of the pig trophoblastic IFNs, since no autocrine effect was found on the trophoblast. It has also been shown that, unlike for the ruminant species, the pig trophoblastic IFNs do not play an apparent role in the so-called maternal recognition of pregnancy. We have focused this review on IFN-gamma, because first, it is the major species secreted and secondly, IFN-gamma has various regulatory effects on different tissues, including lymphoid cells. We particularly address the question of the possible role of trophoblastic IFN-gamma in early pregnancy, in the light of the known biological functions of human and mouse IFN-gamma.     

The uterus and early pregnancy failure in the mare

The environment the equine conceptus finds itself in when it arrives in the uterus some 6 days after ovulation will determine if it will thrive or die. The uterus will be its home for approximately the next 11 months and as such it needs to both coordinate the growth of the placenta and ensure there is enough nourishment passing to this organ for the fetus to develop normally. The trophoblast, endometrium, maternal ovaries and, later in pregnancy, the fetal gonads, all play roles in the hormonal changes that orchestrate these events. Although failures of these processes later in pregnancy can have catastrophic effects for the fetus, it is in early gestation that the foundations for a successful pregnancy are laid. This paper therefore concentrates on some of the noninfectious influences the uterus may have on survival of the young conceptus.     

Expression of uterine sensitization-associated gene-1 (USAG-1) in the mouse uterus during the peri-implantation period

Rat uterine sensitization-associated gene-1 (USAG-1) mRNA is expressed in the uterus during the peri-implantation period, and its mRNA expression in uterine epithelial cells is highest on day 5 of pregnancy. On the other hand, since changes in USAG-1 mRNA expression in the mouse uterus are not seen during the estrous cycle, USAG-1 expression might be specifically regulated by embryonic factors rather than by the maternal environment. However, the expression pattern and function of USAG-1 in the mouse uterus have not been determined. Thus, we examined the tissue-specific USAG-1 mRNA expression in the uteri of ICR mice during peri-implantation using real-time quantitative PCR. Uterine tissues, such as the myometrium, luminal epithelium, and stroma, were collected by laser capture microdissection at 3.5-6.5 dpc. USAG-1 mRNA was expressed in the uteri of pregnant mice from 3.5 dpc to 6.5 dpc, and the highest level of expression was seen at 4.5 dpc (P<0.01). Significantly high USAG-1 mRNA expression was detected in the luminal epithelium at 4.5 dpc (P<0.05). The stroma and myometrium exhibited unchanged expression levels of USAG-1 mRNA at 3.5-5.5 dpc. USAG-1 mRNA was undetectable in blastocysts and implanting embryos. Expression of USAG-1 mRNA appears to be associated with blastocyst implantation to the luminal epithelium, suggesting that physiological or biochemical contact of the blastocyst to the uterus is required for USAG-1 expression.     

Embryonic Signals and Survival

The objective of this review is to give an overview of the signaling mechanisms between the conceptus and the mother before implantation. The interactions between the embryo and uterus are complex and essential for normal embryo development and implantation. Problems in the signaling mechanisms are thought to play a significant role in early embryonic mortality since a high rate of embryonic morality occurs during this period. This review will focus on the mechanisms involved in the development of the conceptus and the prevention of luteolysis. It is based primarily on what is known in ruminants but also refers to work in other species such as the mouse and primates.     

Expression Pattern of CD34 at the Maternal–Foetal Interface During Pregnancy in Pigs

The pig exhibits a non‐invasive, epitheliochorial placentation. Adhesion molecules are indispensable for successful implantation and establishment of placentation. CD34 is an adhesion molecule belonging to the immunoglobulin superfamily (IgSF). To take the first step to investigate the role of CD34 in placentation, we examined the expression pattern of CD34 at the maternal–foetal interface in Yorkshire gilts on days 15, 26, 50 or 95 and in Meishan gilts on days 26, 50 or 95 of pregnancy (n = 3 gilts/breed/day of pregnancy) by immunohistochemical technique. The CD34‐positive signals were detected in uterine luminal epithelium and trophectoderm in Yorkshire pigs; the staining for CD34 was located in trophectoderm but barely detectable at the uterine luminal epithelium on day 15 of pregnancy. Then, the expression of CD34 increased dramatically in both the uterine luminal epithelium and trophectoderm by day 26, and weak staining intensity was observed at the maternal–foetal interface on days 50 and 95 of pregnancy. The expression pattern of CD34 in Meishan pigs is similar to that in Yorkshire pigs except that only a few positive signals were observed at the luminal epithelium on day 26 of pregnancy. These results suggest that CD34 may be involved in mediating the cell‐to‐cell adhesion between trophectoderm and the luminal epithelial cells during early pregnancy in pigs.