Activin and inhibin signaling: From regulation of physiology to involvement in the pathology of the female reproductive system

Adu‐Gyamfi, Enoch Appiah; Djankpa, Francis Tanam; Nelson, William; Czika, Armin; Sah, Sanjay Kumar; Lamptey, Jones; Ding, Yubin; Wang, Yingxiong

doi:10.1016/j.cyto.2020.155105

Cited by 36 publications

(40 citation statements)

References 165 publications

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“…Each of these stages of placentation is regulated by a plethora of cytokines, growth factors, hormones, and proteins. Abnormal expression of these molecules lead to abnormal placentation and its associated pathologies [1][2][3][4][5][6][7][8]. In this review, we have aggregated the up-to-date evidence about the expression patterns of the cell adhesion molecules, tight junctions, and gap junctions in the various trophoblast lineages during physiological and pathological placentation; and have explained how they regulate trophoblast proliferation, trophoblast fusion, trophoblast migration, trophoblast invasion, glandular remodeling, and spiral artery remodeling, which are the major phases of human placentation.…”

Section: Introductionmentioning

confidence: 99%

The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation

et al. 2020

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Placentation is a major determinant of the success of pregnancy. It is regulated by several factors such as cell adhesion molecules, tight junctions, and gap junctions. The cell adhesion molecules are integrins, cadherins, immunoglobulins, nectins, and selectins. The tight junctions are composed of claudins, occludin, and junction adhesion molecule proteins while the gap junctions are composed of connexins of varying molecular weights. During placentation, some of these molecules regulate trophoblast proliferation, trophoblast fusion, trophoblast migration, trophoblast invasion, trophoblastendothelium adhesion, glandular remodeling, and spiral artery remodeling. There is a dysregulated placental expression of some of these molecules during obstetric complications. We have, hereby, indicated the expression patterns of the subunits of each of these molecules in the various trophoblast subtypes and in the decidua, and have highlighted their involvement in physiological and pathological placentation. The available evidence points to the relevance of these molecules as distinguishing markers of the various trophoblast lineages and as potential therapeutic targets in the management of malplacentation-mediated diseases.

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Section: Introductionmentioning

confidence: 99%

The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation

et al. 2020

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“…Activins and inhibins are dimeric proteins belonging to the TGF-β superfamily that stimulate and inhibit the pituitary FSH secretion, respectively [ 46 ]. They also regulate many other biological processes including germ cell development, follicle maturation, ovulation, and uterine receptivity [ 47 ]. Mice with a targeted deletion of Inha , the gene of Inhibin-α, which is the common monomeric subunit shared by Inhibin A and B proteins [ 46 ], were infertile and developed gonadal tumors in both males and females.…”

Section: Genes and Pathways Involved In The Maintenance Of The Female Cell Fatementioning

confidence: 99%

“…In these mutant mice, initial gonadal development was normal but their ovaries presented nodules of seminiferous-like tubules with Sertoli-like cells at 6–8 weeks [ 48 ]. Follistatin (FST) is a glycoprotein that cooperates with inhibins in neutralizing activins and pituitary FSH repression [ 47 , 49 , 50 ]. Granulosa cell-specific deletion of Fst in mice also led to reduced fertility with adult ovaries showing some seminiferous-like testis cords [ 51 ].…”

Section: Genes and Pathways Involved In The Maintenance Of The Female Cell Fatementioning

confidence: 99%

Sex Maintenance in Mammals

Jiménez

Burgos

Barrionuevo

2021

Genes

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The crucial event in mammalian sexual differentiation occurs at the embryonic stage of sex determination, when the bipotential gonads differentiate as either testes or ovaries, according to the sex chromosome constitution of the embryo, XY or XX, respectively. Once differentiated, testes produce sexual hormones that induce the subsequent differentiation of the male reproductive tract. On the other hand, the lack of masculinizing hormones in XX embryos permits the formation of the female reproductive tract. It was long assumed that once the gonad is differentiated, this developmental decision is irreversible. However, several findings in the last decade have shown that this is not the case and that a continuous sex maintenance is needed. Deletion of Foxl2 in the adult ovary lead to ovary-to-testis transdifferentiation and deletion of either Dmrt1 or Sox9/Sox8 in the adult testis induces the opposite process. In both cases, mutant gonads were genetically reprogrammed, showing that both the male program in ovaries and the female program in testes must be actively repressed throughout the individual’s life. In addition to these transcription factors, other genes and molecular pathways have also been shown to be involved in this antagonism. The aim of this review is to provide an overview of the genetic basis of sex maintenance once the gonad is already differentiated.

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“…We hypothesize that the rare heterozygous variant detected in INHA could contribute to POI because INHA is a known POI susceptibility locus and a recurrent missense heterozygous variant (c.769G>A; p.A257T) has been reported in POI cases in several populations 2 . INHA encodes the alpha subunit of inhibins A and B 17 . Inhibins are dimeric glycoprotein hormones belonging to the superfamily of TGF‐β 17 .…”

Section: Discussionmentioning

confidence: 99%

“…INHA encodes the alpha subunit of inhibins A and B 17 . Inhibins are dimeric glycoprotein hormones belonging to the superfamily of TGF‐β 17 . Even if INHA is permissive to heterozygous pathogenic variants (low pLI and high o/e according to gnomAD), we cannot exclude the existence of deleterious or slightly deleterious dominant negative variants 18 .…”

Section: Discussionmentioning

confidence: 99%

An exome‐wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes

Álvarez-Mora¹,

Todeschini

Caburet

et al. 2020

Clinical Genetics

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Primary ovarian insufficiency (POI) implies the cessation of menstruation for several months in women before the age of 40 years and is a major cause of infertility. The study of the contribution of genetic factors to POI has been fueled by the use of whole exome sequencing (WES). Here, to uncover novel causative pathogenic variants and risk alleles, WES has been performed in 12 patients with familial POI (eight unrelated index cases and two pairs of sisters) and six women with early menopause and family history of POI (four index cases and one pair of sisters). Likely causative variants in NR5A1 and MCM9 genes were identified as well as a variant in INHA that requires further investigation. Moreover, we have identified more than one candidate variant in 3 out of 15 familial cases. Taken together, our results highlight the genetic heterogeneity of POI and early menopause and support the hypothesis of an oligogenic inheritance of such conditions, in addition to monogenic inheritance.

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Activin and inhibin signaling: From regulation of physiology to involvement in the pathology of the female reproductive system

Cited by 36 publications

References 165 publications

The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation

The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation

Sex Maintenance in Mammals

An exome‐wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes

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