Biology of uterine glands : impact on reproductive function

2018 ◽  
Author(s):  
◽  
Andrew Michael Kelleher

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Pregnancy loss is the most common complication of human gestation, and roughly one-half of conceptions result in pregnancy loss, most frequently in the first two weeks of gestation. In humans, uterine gland dysfunction is thought to result in pregnancy loss and complications, such as preeclampsia, and fetal growth restriction. Available studies in mice support the hypothesis that uterine glands and forkhead box A2 (FOXA2), a uterine gland specific transcription factor, have important biological roles in blastocyst attachment, implantation, and stromal cell decidualization. Thus, aims of this dissertation included: (1) interrogation of the uterine transcriptome and secretome with and without uterine glands during the periimplantation period of pregnancy; and (2) elucidation of the impact of uterine glands and FOXA2 on endometrial receptivity, blastocyst implantation, and stromal cell decidualization. Those objectives were addressed by utilizing mouse models lacking uterine glands and/or FOXA2 in conjunction with in-depth histomorphological, transcriptomic and proteomic analysis. Results of these studies established: (1) uterine glands substantially impact homeostasis of the uterine environment; (2) leukemia inhibitory factor (LIF), and other gland-derived products, are not present within the uterine fluid during the periimplantation period; (3) FOXA2 regulates uterine expression of Lif; (4) LIF-repletion is sufficient for pregnancy establishment but not maintenance in glandless mice; (5) FOXA2- independent uterine gland-derived factors are required for a successful pregnancy. Collectively, these studies provide original evidence that uterine glands are critical for synchronous embryo-endometrial interactions and coordinate on-time implantation and stromal cell decidualization, thereby impacting embryo viability and pregnancy success. These studies also identified novel glandular factors that may be of significance to implantation and post-implantation processes in mice and humans.

2018 ◽  
Author(s):  
◽  
Andrew Michael Kelleher

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Pregnancy loss is the most common complication of human gestation, and roughly one-half of conceptions result in pregnancy loss, most frequently in the first two weeks of gestation. In humans, uterine gland dysfunction is thought to result in pregnancy loss and complications, such as preeclampsia, and fetal growth restriction. Available studies in mice support the hypothesis that uterine glands and forkhead box A2 (FOXA2), a uterine gland specific transcription factor, have important biological roles in blastocyst attachment, implantation, and stromal cell decidualization. Thus, aims of this dissertation included: (1) interrogation of the uterine transcriptome and secretome with and without uterine glands during the periimplantation period of pregnancy; and (2) elucidation of the impact of uterine glands and FOXA2 on endometrial receptivity, blastocyst implantation, and stromal cell decidualization. Those objectives were addressed by utilizing mouse models lacking uterine glands and/or FOXA2 in conjunction with in-depth histomorphological, transcriptomic and proteomic analysis. Results of these studies established: (1) uterine glands substantially impact homeostasis of the uterine environment; (2) leukemia inhibitory factor (LIF), and other gland-derived products, are not present within the uterine fluid during the periimplantation period; (3) FOXA2 regulates uterine expression of Lif; (4) LIF-repletion is sufficient for pregnancy establishment but not maintenance in glandless mice; (5) FOXA2- independent uterine gland-derived factors are required for a successful pregnancy. Collectively, these studies provide original evidence that uterine glands are critical for synchronous embryo-endometrial interactions and coordinate on-time implantation and stromal cell decidualization, thereby impacting embryo viability and pregnancy success. These studies also identified novel glandular factors that may be of significance to implantation and post-implantation processes in mice and humans.


2017 ◽  
Vol 114 (6) ◽  
pp. E1018-E1026 ◽  
Author(s):  
Andrew M. Kelleher ◽  
Wang Peng ◽  
James K. Pru ◽  
Cindy A. Pru ◽  
Francesco J. DeMayo ◽  
...  

Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model. The uteri of adult FOXA2-deleted mice were morphologically normal and contained glands, whereas the uteri of neonatal FOXA2-deleted mice were completely aglandular. Notably, adult FOXA2-deleted mice are completely infertile because of defects in blastocyst implantation and stromal cell decidualization. Leukemia inhibitory factor (LIF), a critical implantation factor of uterine gland origin, was not expressed during early pregnancy in adult FOXA2-deleted mice. Intriguingly, i.p. injections of LIF initiated blastocyst implantation in the uteri of both gland-containing and glandless adult FOXA2-deleted mice. Although pregnancy was rescued by LIF and was maintained to term in uterine gland-containing adult FOXA2-deleted mice, pregnancy failed by day 10 in neonatal FOXA2-deleted mice lacking uterine glands. These studies reveal a previously unrecognized role for FOXA2 in regulation of adult uterine function and fertility and provide original evidence that uterine glands and, by inference, their secretions play important roles in blastocyst implantation and stromal cell decidualization.


2019 ◽  
Vol 7 (1) ◽  
pp. 125-147 ◽  
Author(s):  
Thomas E. Spencer ◽  
Andrew M. Kelleher ◽  
Frank F. Bartol

All mammalian uteri contain glands that synthesize or transport and secrete substances into the uterine lumen. Uterine gland development, or adenogenesis, is uniquely a postnatal event in sheep and pigs and involves differentiation of glandular epithelium from luminal epithelium, followed by invagination and coiling morphogenesis throughout the stroma. Intrinsic transcription factors and extrinsic factors from the ovary and pituitary as well as the mammary gland (lactocrine) regulate uterine adenogenesis. Recurrent pregnancy loss is observed in the ovine uterine gland knockout sheep, providing unequivocal evidence that glands and their products are essential for fertility. Uterine gland hyperplasia and hypertrophy during pregnancy are controlled by sequential actions of hormones from the ovary and/or pituitary as well as the placenta. Gland-derived histotroph is transported by placental areolae for fetal growth. Increased knowledge of uterine gland biology is expected to improve pregnancy outcomes, as well as the health and productivity of mothers and their offspring.


2016 ◽  
Vol 3 (2) ◽  
pp. 56-62
Author(s):  
R. Iskra ◽  
V. Vlizlo ◽  
R. Fedoruk

The results of our studies and the data of modern literature regarding the biological role of Cr(III) compounds in conditions of their application in the nutrition for pigs and cattle are discussed. The metabolic impact of Cr(III), coming from different sources – mineral and organic compounds, obtained by chemical synthesis or a nanotechnological method (chromium citrate), as well as in the form of biocomplexes from the cultural medium of Saccharomyces cerevisiae yeasts was analyzed. The metabolic connection between the impact of Cr(III) and the biosynthesis of some hormones – insulin, cortisol – as well as the sensitivity of some tissues and organs to the effect of chromium compounds was studied. A considerable part of the review material was dedicated to the metabolic effect of Cr(III) compounds on the reproductive function of pigs and cattle and their impact on the viability of the offspring and gametes of animals. The data about the stimulating effect of Cr(III) on the growth and development of the organism of piglets and calves, meat and milk performance of these species of animals are discussed. The relevance of dosing Cr(III) in the nutrition of pigs and cattle is highlighted.


2017 ◽  
Vol 68 (6) ◽  
pp. 1381-1383
Author(s):  
Allia Sindilar ◽  
Carmen Lacramioara Zamfir ◽  
Eusebiu Viorel Sindilar ◽  
Alin Constantin Pinzariu ◽  
Eduard Crauciuc ◽  
...  

Endometriosis is described as a gynecological disorder characterized by the presence of endometrial tissue outside the uterus; extensively explored because of its increasing incidency, with an indubitable diagnostic only after invasive surgery, with no efficient treatment, it has still many aspects to be elucidated. A growing body of facts sustain oxidative stress as a crucial factor between the numerous incriminated factors implicated in endometriosis ethiopathogeny. Reactive oxygen species(ROS) act to decline reproductive function. Our study intends to determine if an experimental model of endometriosis may be useful to assess the impact of oxidative stress on endometrial cells; we have used a murine model of 18 adult Wistar female rats. A fragment from their left uterine horn was implanted in the abdominal wall. After 4 weeks, a laparatomy was performed, 5 endometrial implants were removed, followed by biochemical tissue assay of superoxide dismutase(SOD) and catalase(CAT). At the end of the experiment, the rats were sacrificed, the implants were removed for histopathological exam and biochemical assay of antioxidant enzymes. The results revealed decreased levels of antioxidant enzymes, pointing on significant oxidative stress involvement.


2019 ◽  
Vol 17 (5) ◽  
pp. 455-464 ◽  
Author(s):  
Alfonso Mate ◽  
Antonio J. Blanca ◽  
Rocío Salsoso ◽  
Fernando Toledo ◽  
Pablo Stiefel ◽  
...  

Pregnancy hypertensive disorders such as Preeclampsia (PE) are strongly correlated with insulin resistance, a condition in which the metabolic handling of D-glucose is deficient. In addition, the impact of preeclampsia is enhanced by other insulin-resistant disorders, including polycystic ovary syndrome and obesity. For this reason, there is a clear association between maternal insulin resistance, polycystic ovary syndrome, obesity and the development of PE. However, whether PE is a consequence or the cause of these disorders is still unclear. Insulin therapy is usually recommended to pregnant women with diabetes mellitus when dietary and lifestyle measures have failed. The advantage of insulin therapy for Gestational Diabetes Mellitus (GDM) patients with hypertension is still controversial; surprisingly, there are no studies in which insulin therapy has been used in patients with hypertension in pregnancy without or with an established GDM. This review is focused on the use of insulin therapy in hypertensive disorders in the pregnancy and its effect on offspring and mother later in life. PubMed and relevant medical databases have been screened for literature covering research in the field especially in the last 5-10 years.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luís Crisóstomo ◽  
Ivana Jarak ◽  
Luís P. Rato ◽  
João F. Raposo ◽  
Rachel L. Batterham ◽  
...  

AbstractThe consumption of energy-dense diets has contributed to an increase in the prevalence of obesity and its comorbidities worldwide. The adoption of unhealthy feeding habits often occurs at early age, prompting the early onset of metabolic disease with unknown consequences for reproductive function later in life. Recently, evidence has emerged regarding the intergenerational and transgenerational effects of high-fat diets (HFD) on sperm parameters and testicular metabolism. Hereby, we study the impact of high-fat feeding male mice (F0) on the testicular metabolome and function of their sons (F1) and grandsons (F2). Testicular content of metabolites related to insulin resistance, cell membrane remodeling, nutritional support and antioxidative stress (leucine, acetate, glycine, glutamine, inosine) were altered in sons and grandsons of mice fed with HFD, comparing to descendants of chow-fed mice. Sperm counts were lower in the grandsons of mice fed with HFD, even if transient. Sperm quality was correlated to testicular metabolite content in all generations. Principal Component Analysis of sperm parameters and testicular metabolites revealed an HFD-related phenotype, especially in the diet-challenged generation and their grandsons. Ancestral HFD, even if transient, causes transgenerational “inherited metabolic memory” in the testicular tissue, characterized by changes in testicular metabolome and function.


2021 ◽  
pp. 141-146
Author(s):  
Reda Youssef ◽  
Gamal Sayed Ahmed ◽  
Samir Alhyassat ◽  
Sanaa Badr ◽  
Ahmed Sabry ◽  
...  

Dysgerminoma is an uncommon malignant tumor arising from the germ cells of the ovary. Its association with pregnancy is extremely rare, with a reported incidence of about 0.2–1 per 100,000 pregnancies. Women in the reproductive age group are more commonly affected. It can be extremely rare to conceive naturally, without assisted reproductive interventions, in cases with ovarian dysgerminoma. If a pregnancy does occur with a concurrent dysgerminoma, it is even more unusual to carry the pregnancy to viability or childbirth without fetal or maternal compromise. We report a case of right ovarian dysgerminoma in a young female with a viable intrauterine pregnancy at 10 weeks, which is rarely diagnosed and managed at this gestational age. Numerous factors played a role in her favorable outcome, including early suspicion by ultrasound and presenting history, surgery, histopathological assessment, imaging, and involvement of the multidisciplinary oncology team. Ovarian neoplasms may rapidly increase in size within a short period with little or no symptoms. This poses a diagnostic challenge for obstetricians and oncologists. Hence, we aimed to evaluate the role of imaging in pregnancy using ultrasound as an imaging modality for both early detection of ovarian neoplasms and for follow-up. In conclusion, patients with ovarian dysgerminoma in pregnancy can have favorable outcomes. Treatment should be individualized on a case-to-case basis, depending on many factors; cancer stage, previous reproductive history, the impact of imaging in staging or follow-up of tumor on the fetus, fetal gestational age, and whether termination of the pregnancy can improve survival or morbidity for the mother.


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