Natural Mating Differentially Triggers Expression of Glucocorticoid Receptor (NR3C1)-Related Genes in the Preovulatory Porcine Female Reproductive Tract

Mating initiates dynamic modifications of gene transcription in the female reproductive tract, preparing the female for fertilization and pregnancy. Glucocorticoid signaling is essential for the homeostasis of mammalian physiological functions. This complex glucocorticoid regulation is mediated through the glucocorticoid receptor, also known as nuclear receptor subfamily 3 group C member 1 (NR3C1/GR) and related genes, like 11β-hydroxysteroid dehydrogenases (HSD11Bs) and the FK506-binding immunophilins, FKBP5 and FKBP4. This study tested the transcriptome changes in NR3C1/GR regulation in response to natural mating and/or cervical deposition of the sperm-peak ejaculate fraction collected using the gloved-hand method (semen or only its seminal plasma), in the preovulatory pig reproductive tract (cervix to infundibulum, 24 h after mating/insemination/infusion treatments). Porcine cDNA microarrays revealed 22 NR3C1-related transcripts, and changes in gene expression were triggered by all treatments, with natural mating showing the largest differences, including NR3C1, FKBP5, FKBP4, hydroxysteroid 11-beta dehydrogenase 1 and 2 (HSD11B1, HSD11B2), and the signal transducer and activator of transcription 5A (STAT5A). Our data suggest that natural mating induces expression changes that might promote a reduction of the cortisol action in the oviductal sperm reservoir. Together with the STAT-mediated downregulation of cytokine immune actions, this reduction may prevent harmful effects by promoting tolerance towards the spermatozoa stored in the oviduct and perhaps elicit spermatozoa activation and detachment after ovulation.

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Distribution of spermatozoa in the female reproductive tract of the domestic cat in relation to ovulation induced by natural mating

Theriogenology ◽

10.1016/j.theriogenology.2003.12.014 ◽

2004 ◽

Vol 62 (6) ◽

pp. 1027-1041 ◽

Cited By ~ 20

Author(s):

Kaywalee Chatdarong ◽

Chainarong Lohachit ◽

Catharina Linde-Forsberg

Keyword(s):

Reproductive Tract ◽

Female Reproductive Tract ◽

Domestic Cat ◽

Natural Mating

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Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1508056112 ◽

2015 ◽

Vol 112 (49) ◽

pp. 15166-15171 ◽

Cited By ~ 38

Author(s):

Shannon D. Whirledge ◽

Robert H. Oakley ◽

Page H. Myers ◽

John P. Lydon ◽

Francesco DeMayo ◽

...

Keyword(s):

Glucocorticoid Receptors ◽

Reproductive Tract ◽

Immune Cell ◽

Steroid Receptors ◽

Embryo Implantation ◽

Female Reproductive Tract ◽

Mouse Uterus ◽

Glucocorticoid Signaling ◽

Endocrine Organs

In addition to the well-characterized role of the sex steroid receptors in fertility and reproduction, organs of the female reproductive tract are also regulated by the hypothalamic–pituitary–adrenal axis. These endocrine organs are sensitive to stress-mediated actions of glucocorticoids, and the mouse uterus contains high levels of the glucocorticoid receptor (GR). Although the presence of GR in the uterus is well established, uterine glucocorticoid signaling has been largely ignored in terms of its reproductive and/or immunomodulatory functions on fertility. To define the direct in vivo function of glucocorticoid signaling in adult uterine physiology, we generated a uterine-specific GR knockout (uterine GR KO) mouse using the PRcre mouse model. The uterine GR KO mice display a profound subfertile phenotype, including a significant delay to first litter and decreased pups per litter. Early defects in pregnancy are evident as reduced blastocyst implantation and subsequent defects in stromal cell decidualization, including decreased proliferation, aberrant apoptosis, and altered gene expression. The deficiency in uterine GR signaling resulted in an exaggerated inflammatory response to induced decidualization, including altered immune cell recruitment. These results demonstrate that GR is required to establish the necessary cellular context for maintaining normal uterine biology and fertility through the regulation of uterine-specific actions.

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Does the Act of Copulation per se, without Considering Seminal Deposition, Change the Expression of Genes in the Porcine Female Genital Tract?

International Journal of Molecular Sciences ◽

10.3390/ijms21155477 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5477

Author(s):

Manuel Alvarez-Rodriguez ◽

Cristina A. Martinez ◽

Dominic Wright ◽

Heriberto Rodriguez-Martinez

Keyword(s):

Gene Expression ◽

Genital Tract ◽

Reproductive Tract ◽

Female Genital Tract ◽

Female Reproductive Tract ◽

Smooth Muscle Contractility ◽

Expression Of Genes ◽

Per Se ◽

Natural Mating ◽

Transcriptomic Changes

Semen—through its specific sperm and seminal plasma (SP) constituents—induces changes of gene expression in the internal genital tract of pigs, particularly in the functional sperm reservoir at the utero-tubal junction (UTJ). Although seminal effects are similarly elicited by artificial insemination (AI), major changes in gene expression are registered after natural mating, a fact suggesting the act of copulation induces per se changes in genes that AI does not affect. The present study explored which pathways were solely influenced by copulation, affecting the differential expression of genes (DEGs) of the pre/peri-ovulatory genital tract (cervix, distal uterus, proximal uterus and UTJ) of estrus sows, 24 h after various procedures were performed to compare natural mating with AI of semen (control 1), sperm-free SP harvested from the sperm-peak fraction (control 2), sperm-free SP harvested from the whole ejaculate (control 3) or saline-extender BTS (control 4), using a microarray chip (GeneChip® porcine gene 1.0 st array). Genes related to neuroendocrine responses (ADRA1, ADRA2, GABRB2, CACNB2), smooth muscle contractility (WNT7A), angiogenesis and vascular remodeling (poFUT1, NTN4) were, among others, overrepresented with distal and proximal uterine segments exhibiting the highest number of DEGs. The findings provide novel evidence that relevant transcriptomic changes in the porcine female reproductive tract occur in direct response to the specific act of copulation, being semen-independent.

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Release of Porcine Sperm from Oviduct Cells is Stimulated by Progesterone and Requires CatSper

Scientific Reports ◽

10.1038/s41598-019-55834-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 13

Author(s):

Sergio A. Machado ◽

Momal Sharif ◽

Huijing Wang ◽

Nicolai Bovin ◽

David J. Miller

Keyword(s):

Reproductive Tract ◽

Sperm Storage ◽

Female Reproductive Tract ◽

Cell Aggregates ◽

Sperm Release ◽

Intracellular Ca ◽

Sperm Reservoir ◽

Hormonal Milieu ◽

Oviduct Cell ◽

Sperm Functions

AbstractSperm storage in the female reproductive tract after mating and before ovulation is a reproductive strategy used by many species. When insemination and ovulation are poorly synchronized, the formation and maintenance of a functional sperm reservoir improves the possibility of fertilization. In mammals, the oviduct regulates sperm functions, such as Ca2+ influx and processes associated with sperm maturation, collectively known as capacitation. A fraction of the stored sperm is released by unknown mechanisms and moves to the site of fertilization. There is an empirical association between the hormonal milieu in the oviduct and sperm detachment; therefore, we tested directly the ability of progesterone to induce sperm release from oviduct cell aggregates. Sperm were allowed to bind to oviduct cells or an immobilized oviduct glycan and then challenged with progesterone, which stimulated the release of 48% of sperm from oviduct cells or 68% of sperm from an immobilized oviduct glycan. The effect of progesterone on sperm release was specific; pregnenolone and 17α-OH-progesterone did not affect sperm release. Ca2+ influx into sperm is associated with capacitation and development of hyperactivated motility. Progesterone increased sperm intracellular Ca2+, which was abrogated by blocking the sperm–specific Ca2+ channel CatSper with NNC 055-0396. NNC 055-0396 also blocked the progesterone-induced sperm release from oviduct cells or immobilized glycan. An inhibitor of the non-genomic progesterone receptor that activates CatSper similarly blocked sperm release. This is the first report indicating that release of sperm from the sperm reservoir is induced by progesterone action through CatSper channels.

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Effect of Contraceptive Steroids on the Endometrium of Guinea Pig: SEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100080766 ◽

1977 ◽

Vol 35 ◽

pp. 668-669

Author(s):

Mai M. Said ◽

Ramesh K. Nayak ◽

Randall E. McCoy

Keyword(s):

Guinea Pig ◽

Reproductive Tract ◽

Three Dimensional ◽

Female Reproductive Tract ◽

Human Female ◽

Surface Ultrastructure ◽

Transmission Electron ◽

Sem Study ◽

Uterine Mucosa ◽

Group 1

Burgos and Wislocki described changes in the mucosa of the guinea pig uterus, cervix and vagina during the estrous cycle investigated by transmission electron microscopy. More recently, Moghissi and Reame reported the effects of progestational agents on the human female reproductive tract. They found drooping and shortening of cilia in norgestrel and norethindrone- treated endometria. To the best of our knowledge, no studies concerning the effects of mestranol and norethindrone given concurrently on the three-dimensional surface features on the uterine mucosa of the guinea pig have been reported. The purpose of this study was to determine the effect of mestranol and norethindrone on surface ultrastructure of guinea pig uterus by SEM.Seventy eight animals were used in this study. They were allocated into two groups. Group 1 (20 animals) was injected intramuscularly 0.1 ml vegetable oil and served as controls.

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Surface ultrastructure of danazol treated rat endometrium: A SEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010007641x ◽

1983 ◽

Vol 41 ◽

pp. 556-557

Author(s):

R.P. Apkarian ◽

J.S. Sanfilippo

Keyword(s):

Cross Sections ◽

Reproductive Tract ◽

Preliminary Investigation ◽

Breast Disease ◽

Distal Segment ◽

Uterine Horn ◽

Female Reproductive Tract ◽

Ultrastructural Changes ◽

Cycle Phase ◽

Sprague Dawley

The synthetic androgen danazol, is an isoxazol derivative of ethisterone. It is utilized in the treatment of endometriosis, fibrocystic breast disease, and has a potential use as a contraceptive. A study was designed to evaluate the ultrastructural changes associated with danazol therapy in a rat model. The preliminary investigation of the distal segment of the rat uterine horn was undertaken as part of a larger study intended to elucidate the effects of danazol on the female reproductive tract.Cross-sections (2-3 mm in length) of the distal segment of the uterine horn from sixteen Sprague-Dawley rats were prepared for SEM. Ten rats in estrus served as controls and six danazol treated rats were noted to have alterations of the estrus cycle i.e. a lag in cycle phase or noncycling patterns. Specimens were fixed in 3% glutaraldehyde in 0.05M phosphate buffer containing CaCl2 at pH 7.0-7.4 and chilled to 4°C. After a brief wash in distilled water, specimens were passed through a graded series of ethanol, critical point dryed in CO2 from absolute ethanol, and coated with 6nm Au. Observations were made with an IS1-40 SEM operated at 15kV.

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The application of electron microscopy to diagnosis in gynecologic neoplasms and tumor-like conditions

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100110787 ◽

1984 ◽

Vol 42 ◽

pp. 102-105

Author(s):

Lawrence M. Roth

Keyword(s):

Electron Microscopy ◽

Reproductive Tract ◽

Malignant Tumors ◽

Frozen Section ◽

Cost Effective ◽

Female Reproductive Tract ◽

Ultrastructural Examination ◽

Specific Diagnosis ◽

Potential Value ◽

Gynecologic Neoplasms

The female reproductive tract may be the site of a wide variety of benign and malignant tumors, as well as non-neoplastic tumor-like conditions, most of which can be diagnosed by light microscopic examination including special stains and more recently immunoperoxidase techniques. Nevertheless there are situations where ultrastructural examination can contribute substantially to an accurate and specific diagnosis. It is my opinion that electron microscopy can be of greatest benefit and is most cost effective when applied in conjunction with other methodologies. Thus, I have developed an approach which has proved useful for me and may have benefit for others. In cases where it is deemed of potential value, glutaraldehyde-fixed material is obtained at the time of frozen section or otherwise at operation. Coordination with the gynecologic oncologist is required in the latter situation. This material is processed and blocked and is available if a future need arises.

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