Progesterone-mediated effects on gene expression and oocyte-cumulus complex transport in the mouse fallopian tube

Abstract

BackgroundThe fallopian tube transports the gametes to the fertilization site and delivers the embryo to the uterus at the optimal time for implantation. Progesterone and the classical progesterone receptor are involved in regulating both tubal ciliary beating and muscular contractions, likely via both genomic and non-genomic actions.MethodsTo provide more details of the underlying mechanisms, we investigated the effect of progesterone on gene expression in mice fallopian tubes in vitro at 20 min, 2 h and 8 h post progesterone treatment using microarray and/or quantitative PCR. In parallel, oocyte cumulus complex transport was investigated in ovulating mice that were injected with one of the progesterone receptor antagonists, Org 31710 or CDB2194.ResultsMicroarray analyses did not reveal any apparently regulated genes 20 min after progesterone treatment, consistent with the proposed non-genomic action of progesterone controlling ciliary beating. After 2 h, 11 genes were identified as up-regulated. Analyses using quantitative PCR at 2 h and 8 h showed a consistent up-regulation of endothelin1 and a down-regulation of its receptor Endothelin receptor A by progesterone. We also confirmed that treatment with progesterone receptor antagonists before ovulation accelerates the transport of the oocyte cumulus complex.ConclusionsThis is the first study showing that progesterone regulates the expression of endothelin1 and endothelin receptor A in the fallopian tube. Together with previous studies of the effects of endothelin on muscular contractions in the fallopian tube, the results from this study suggest that endothelin is a mediator of the progesterone-controlled effects on muscular contraction and eventually gamete transport in the fallopian tube.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-015-0038-8) contains supplementary material, which is available to authorized users.

Symposium review: Progesterone effects on early embryo development in cattle

“…Saint-Dizier et al (2012) described expression of nuclear P4 receptor (PGR) and P4 receptor membrane components 1 and 2 in the oviduct of cyclic and pregnant cows during the post-ovulation period, suggesting that P4 regulates the functions of the bovine oviduct in a region-specific manner and through both classical and nonclassical pathways during the post-ovulation period. Bylander et al (2015) reported that P4 regulates the expression of endothelin 1 and endothelin receptor A in the mouse oviduct, which, together with previous studies of the effects of endothelin on muscular contractions in the oviduct, suggests that endothelin is a mediator of the P4-controlled effects on muscular contraction and eventually gamete transport in the fallopian tube. A large number of genes are affected in PGR knockout mouse oviducts during the periovulatory period that may have a role in oocyte capture and transport after ovulation (Akison and Robker 2012).…”

Estradiol and Progesterone Induced Differentiation and Increased Stemness Gene Expression of Human Fallopian Tube Epithelial Cells

“…Because the fallopian tube is exposed to cyclical hormone changes, mechanisms to ensure its long-term renewal and integrity are critical. In addition, estrogen and progesterone have crucial effects on the antiapoptosis, proliferation, contraction, and cytokine production of the FTE 24-27. The fallopian tube could express ERβ and PRs 40,41.…”

“…Both estrogen and progesterone have crucial effects on the antiapoptosis, proliferation, contraction, and cytokine production in the FTE 24-27. A report indicated that progesterone could induce necroptosis in p53-defective FTECs and prevent the occurrence of HGSOC.…”

Identification of new progestogen-associated networks in mammalian ovulation using bioinformatics

“…Regulations of hormones and steroidogenesis are regarded as an initiation process, which provides detailed fundamental information on the profound changes regulated by gene networks in ovulation. Hormone (FSH and LH) induced primary follicle maturation and eventually approached the pre-ovulatory stage in mice and rats [ 2 , 26 ]. Pituitary-released LH forms the LH surge which subsequently initiates the estrous cycle in rodents in response to the high levels of estrogen [ 27 ].…”

“…These genes are considered important in regulating features involved in the progestogenic network or as downstream factors of the network. Genes involved in each pathway may act in concert with accomplishing distinct processes during ovulation including prostaglandin synthesis ( Ptgs2 and PLA2G4A ) [ 7 ], cholesterol uptake ( Ldlr and Scarb1 ) [ 37 ], regulation of progesterone synthesis ( Star ) [ 30 ], inactivation of estrogen ( Sult1e1 ) [ 38 ], and downstream effectors of LH signaling ( Pgr , Cebpb , Areg , Ereg , and Adamts1 ) [ 6 , 26 , 29 , 39 ]. These processes regulate inflammation, follicle-wall degradation, hormone balance and the induction of certain paracrine factors.…”