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Uterine embryo implantation: the endometrium, seminal plasma

the endometrium, seminal plasma
Authors: Catalini, Laura;

Uterine embryo implantation: the endometrium, seminal plasma

Abstract

Omkring 17,5% af verdens voksne befolkning oplever fertilitetsproblemer. Selvom der er en rivende udvikling inden for feltet, er manglende implantation i livmoderen ikke sjældent en begrænsende faktor. Forudsætninger for succesfuld implantation af et normalt udviklet befrugtet æg (embryon) og en modtagelig livmoderslimhinde (endometrium), som er under indflydelse af hormonelle, genetiske og immunologiske faktorer. Formålet med denne afhandling var at studere livmoderslimhinden, dens immunologiske profil, og effekten af sædvæske på livmoderslimhindens modtagelighed for implantation af et embryon. Afhandlingen var baseret på fem studier.Det første studium var et litteratur-studium af menstruerende dyrearter mhp. at identificere mulige dyremodeller for den humane menstruationscyklus og forplantning. Vi fokuserede på menstruationscyklus’ længde, ægløsning, implantation, moderkageudvikling og livmoderslimhindens karakteristika og disses ligheder med menneskets menstruationscyklus.Andet og tredje studium fokuserede på forskellene i udkomme, når der bruges sædceller fra henholdsvis donor og egen partner samt på sædvæskens betydning for livmoderslimhindens udvikling og implantation af det befrugtede æg i livmoderen. Andet studium var et kohorte-studium baseret på nationale, danske sundhedsregistre. Vores resultater viste, at fleste kvinder anvendte donorsædhavde lige så gode graviditetschancer som kvinder anvendte mandlig partnerædhavde, Det tredje studium var et randomiseret, dobbelt-blindet, placebo-kontrolleret forsøg, hvor man undersøgte ændringerne i den såkaldte endometrie transkriptionsprofil efter vaginal applicering af sædvæske. Vi fandt, at sædvæsken stimulerede livmoderslimhinden, idet gener relateret til immunrespons, celledeling, ægmodning, fosterudvikling og kar-nydannelse blev opreguleret.Fjerde og femte studium fokuserede på immunsystemets rolle i implantationsprocessen og dets betydning for graviditetsudkommet. Det fjerde studium var et litteratur-studium, hvor man undersøgte chancerne for at få et levendefødt barn efter assisteret reproduktion (ART) hos kvinder med kroniske sygdomme sammenlignet med andre kvinder, som fik ART af andre årsager. Kvinder med colitis ulcerosa, morbus Crohn, rheumatoid arthritis, hyperthyreodisme og diabetes mellitus type 2 havde lavere graviditetschance pga. lavere implantationschance eller negativ påvirkning af den tidlige fosterudvikling. Kvinder i behandling forhypothyreoidisme, diabetes mellitus type 1 eller epilepsi havde samme graviditetschance som andre kvinder i ART-behandling. Det femte studium var et pilot case-kontrol studium, hvor man, i forbindelse med ART behandling, undersøgte cytokin-profiler i livmoderslimhinden hos kvinder med eller uden autoimmun sygdom. Vi fandt ingen signifikante forskelle mellem grupperne, men kvinder med forskellige autoimmune sygdomme udviste forskellige cytokin-mønstre, som det er værd at studere nærmere.

Infertility is an increasing health challenge affecting around 17.5% of the world's adult population. Despite the continuous improvement in the field of medically assisted reproduction, the implantation rate is still a limiting factor. Successful implantation requires a good-quality embryo and a receptive endometrium influenced by hormonal, genetic and immunological factors. This thesis aim was to study the endometrium, its immune profile and the effect of seminal plasma on endometrial receptivity. The thesis was based on five studies.The first study was a literature review of menstruating animal species in which we provided an overview of possible animal models to study the human menstrual cycle and reproduction. We focused on the length of their menstrual cycle, ovulation, implantation, placentation, decidualization, endometrial characteristics and similarity with human menstrual cycle. The second and third studies focused on the differences between using donor or partner sperm and the importance of seminal plasma in endometrial stimulation and implantation. The second study was a nationwide cohort study based on Danish health registries related to medically assisted reproduction (MAR) in women who used partner or donor sperm. Our results showed that most women using donor sperm have comparable or even better results than women using male partner sperm. The third study was a randomized, double-blinded, placebocontrolled trial where we investigated changes in the endometrial transcriptomic profile after vaginal application of seminal plasma. We found that seminal plasma stimulated the endometrium, upregulating gene pathways related to the immune response, cell proliferation, embryo development, oocyte maturation and angiogenesis.The fourth and fifth studies focused on the immune system's role in implantation and pregnancy success. The fourth study was a literature review in which we investigated the chance of having a live-born child after assisted reproductive technology (ART) in women with chronic diseases, compared to other women in the general population receiving ART. Women with ulcerative colitis, Crohn's disease, rheumatoid arthritis, hyperthyroidism, and diabetes mellitus type 2 had lower chances due to low implantation rate or early embryo development during ART. Women with hypothyroidism, diabetes mellitus type 1, and epilepsy had the same success rate as other women undergoing ART. The fifth study was a pilot case-control study investigating the endometrial cytokine profiles of women undergoing ART with or without autoimmune diseases. We found no significant difference between the groups, but women with different autoimmune diseases showed different cytokine patterns, which are worth further study.

Country
Denmark
Related Organizations
Keywords

fertility, immune system, autoimmune diaseases, seminal plasma, implantation, endometrium

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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Average
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