# INFERTILITY AND TESTICULAR AUTOIMMUNITY

> **NIH NIH R01** · BRIGHAM YOUNG UNIVERSITY · 1994 · $113,377

## Abstract

The results of both clinical and experimental studies suggest
that immunologic mechanisms may be significant in the pathogenesis of
idiopathic infertility.  The long term goal of this research is to define
and characterize the various immunoregulatory genes which control the
phenotypic expression of infertility associated with autoimmune disease
of the testis.  The focus of this application is the characterization of
the murine major histocompatibility complex (H-2) linked immune response
(Ir) gene Orchitis susceptibility gene-1 (Orch-1).  The Orch-I locus
controls the phenotypic expression of both autoimmune reactions in the
testis as well as associated infertility.  Observations made in this
laboratory indicate that recombinations within the H-2S/H-2D interval (a
distance of approximately 700 kb) define the map position of Orch-1.  A
comparison of the Orch-I alleles with other markers known to map within
the same interval suggests the following gene order
H-2S--TNP-Ficoll--Orch-l--TNF--H-2D.  Detailed molecular analysis of the
interval encoding Orch-1 will be obtained by restriction fragment length
polymorphism (RFLP) mapping utilizing existing human cDNAs cloned from
this region.  Subsequently, a set of overlapping cosmids spanning the
Orch-I locus will be isolated.  Nonrepetitive sequences from these clones
will then be used as probes to analyze recombination break points within
the interval and to identify RFLPs among the recombinants whose Orch-I
haplotypes are known with the ultimate long term goal being the
identification, cloning and sequencing of the Orch-I gene.  In addition,
preliminary characterization of the mechanism of action of Orch-I will be
carried out using bone marrow radiation chimera protocols to map the
immunoregulatory effects governed by Orch- 1 to either the bone
marrow-derived or target organ compartment.  Similarly, both azoospermia
and autoimmune responses to sperm and testis antigens have been reported
to be associated with the major histocompatibility complex in humans
(HLA).  Therefore, we postulate that a human Ir gene analogous to Orch-I
exists and that it may play a role in the genetic control of auto- and
isoimmune responses to sperm and testis antigens in man.  The findings of
this research should greatly extend our understanding of the relationship
between such Ir genes and their mechanisms of action and will undoubtedly
extend our understanding of human infertility and autoimmune phenomena.

## Key facts

- **NIH application ID:** 2198367
- **Project number:** 5R01HD021926-08
- **Recipient organization:** BRIGHAM YOUNG UNIVERSITY
- **SAM.gov UEI:** JWSYC7RUMJD1
- **Principal Investigator:** CORY TEUSCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $113,377
- **Award type:** 5
- **Project period:** 1990-07-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198367

## Citation

> US National Institutes of Health, RePORTER application 2198367, INFERTILITY AND TESTICULAR AUTOIMMUNITY (5R01HD021926-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198367. Licensed CC0.

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