Comparative Aspects of Reproductive Failure : An International Conference at Dartmouth Medical School, Hanover, N.H.¿July 25¿29, 1966

To many, the contents of this conference may not seem appropriate at a time when the minds are preoccupied with a "population explosion." To the participants and guests of this conference, however, this was a week of fascinating discussions. While quantitative aspects of reproduc­ tion were touched upon, it was mostly a search for an understanding of the qualitative aspects of reproduction and its failure. Only when we understand these more completely will it be possible to render optimum care and have the foundations for meaningful population control. The conference was conceived in discussions at the Committee on Pathology of the National Academy of Sciences, W"ashington, in 1965. It was felt that investigators in medicine and the veterinary fields would profit greatly from a closer liaison. All too frequently, we work relatively isolated in our respective fields and, with the burgeoning information filling our journals, we have not enough time and leisure to stand back and attempt a comparative look at the subject of study. Often we are not familiar with the techniques other disciplines use, and which we could well employ to great advantage. ,,yhile this applies to many aspects of medicine, a comparative approach to the study of reproductive failure seemed most advantageous at this time.

to Comparative Reproduction.- Seasonality of reproduction.- The egg.- Implantation and placentation.- The neonate.- Comparative values.- The Overall Problem in Man.- Pathogenesis of abortion.- Defective segmenting ova.- Ova consisting of trophoblast only.- Ova containing no chorionic cavity.- Ova showing hypoplasia of trophoblast.- Superficial implantation of an otherwise reasonably normal ovum.- Spontaneous abortion.- Ovular factors.- Pathologic ova.- Embryos with localized anomalies.- Placental abnormalities.- Maternal factors.- Criminal abortion.- Uterine abnormalities.- Febrile and inflammatory diseases.- Miscellaneous.- Anatomically normal ova.- Reproductive Failure in Domestic Mammals.- Failure in ovarian functions.- Anestrus.- Seasonal anestrus.- Anestrus during lactation.- Anestrus due to aging.- Ovarian hypoplasia.- Abnormal estrus.- “Quiet ovulation”.- Cystic ovaries.- Nymphomania.- Fertilization failure and atypical fertilization.- Fertilization failure.- Aged and abnormal ova.- Aged and abnormal sperm.- Atypical fertilization.- Prenatal mortality.- Physiological mechanismsimplantation.- Endocrine factors.- Causes of prenatal mortality.- Age of dam.- Nutrition of dam.- Heredity.- Overcrowding in utero.- Thermal stress.- Semen quality.- Other pregnancy disorders.- Spontaneous abortion.- Metabolic disorders of pregnancy.- Immunological incompatibility.- Fetal mummification.- Retained placenta.- Perinatal mortality.- Neonatal mortality.- Environmental stress and reproductive failure.- Climatic stress.- Nutritional stress.- Plant estrogens.- Anatomical stress and hereditary defects.- Congenital and acquired defects.- Hereditary defects.- Intersexuality.- Freemartinism.- Physiological mechanisms of the syndrome.- Hormonal theory.- Sex-chromosome mosaicism theory.- Diagnosis of freemartinism.- True hermaphrodites.- Comparative aspects.- Pseudohermaphroditism.- Male pseudohermaphrodite.- Female pseudohermaphrodite.- Pathogens and reproductive failure.- Bacterial infections.- Future investigations.- Cytogenetics of Abortions.- Materials and method.- Results.- Discussion.- Summary.- Genetic and Biochemical Aspects of Reproductive Failure.- Inborn errors of metabolism.- Homozygous lethals in man.- The development of enzyme systems.- Embryogenesis and organogenesis.- Chemo-Mechanics of Implantation.- Historical remarks on implantation.- Muscular stage—transport, spacing.- Adhesive stage.- Invasive stage.- Interactions of maternal and embryonic factors.- Summary.- Comparative Aspects of Steroid Hormones in Reproduction.- Possible roles for the steroid hormones in control of gestation.- Implantation.- Pituitary inhibition.- Maintenance of decidua and the endometrial implantation site.- Myometrial tone and contractility.- Length of gestation.- Mammary function.- Metabolic effects.- Summary on the role of steroid hormones in gestation.- The role of the corpus luteum in pregnancy.- Steroid endocrine role of the placenta.- Progesterone.- Estrogens.- Estrogen synthesis by the placenta.- Steroid biosynthesis by the human placenta—The feto-placental unit.- Relationship of steroid hormones to pregnancy failures.- Summary.- Protein Hormones and Gestation.- Human chorionic gonadotrophin.- History.- Biologic effects.- Rate of excretion by biologic assays.- Rate of excretion by immunologic assays.- Natural role of HCG in pregnancy.- Human placental lactogen.- History.- Biologic effects.- Luteotrophic effect.- Somatotrophic effect.- Assay and quantitation.- Extrapituitary gestational gonadotrophins in other mammals.- Prolonged Gestation.- Abnormally long gestation in cattle.- Genetic factors.- Pituitary-adrenal factors.- Abnormally long gestation in sheep.- Experimental prolonged gestation.- Fetal pituitary destruction.- Fetal adrenalectomy.- Conclusions.- Oögenesis—Ovulation and Egg Transport.- Oögenesis.- Origin of primordial germ cells.- Commencement of meiosis.- Development of follicular cells.- Ovulation.- Hormone interaction.- Increase in follicular cells.- Antrum formation.- Displacement of egg.- Increase of follicular size.- Theca cell changes.- Consideration of pressure changes within follicle.- Egg transport.- Anatomy of fallopian tube.- Mechanism of movement of egg into the fallopian tube.- Mechanism of transport of egg through the fallopian tube.- Hormonal regulation of tubal activity.- Experimental Hybridization.- Rabbit × hare hybrid experiments.- Ferret × mink hybrid experiments.- Goat × sheep hybrid experiments.- Embryo transfer.- Analysis of possible causes of intrauterine death of hybrids.- Chromosomes of hybrids.- Hormonal and immunological interactions.- Summary.- Sterility and Fertility of Interspecific Mammalian Hybrids.- Equine chromosome morphology.- Karyotypes of major members of equidae.- Equine hybrids.- Bear chromosomes and hybrids.- Chromosomes of American and Asiatic Camelidae.- Normal structure.- Hybrids.- Canine chromosomes and hybrids.- Cervidae and hybrids.- Other interspecific hybrids.- Conclusions.- Summary.- The Sterility of Two Rare Equine Hybrids.- Material and methods.- Results.- Histology of the testis.- Chromosome studies.- Steroid determinations in testicular tissue.- Discussion.- Developmental Malformations as Manifestations of Reproductive Failure.- The placental membrane plays a complex role in the etiology of mammalian malformations.- Mumps virus.- Rat virus.- Herpes simplex virus.- H-1 virus.- There is a specific Teratogen: organ response.- Synteratogens and proteratogens.- Malformations and Defects of Genetic Origin in Domestic Animals.- The skeleton.- Entire skeleton.- The head.- The axial skeleton.- The appendicular skeleton.- The integument.- Digestive tract.- Reproduction.- Others.- Discussion.- Summary.- Bacterial Infertility in Domestic Animals.- Brucellosis.- Vibriosis.- Leptospirosis.- Listeriosis.- Summary.- Fetal Infections in Man.- Pathogenesis of fetal infections.- Clinical implications.- Correlative studies of placentitis.- Closing comments and hypothesis.- Toxoplasmosis.- Microbe.- Infection.- Acute toxoplasmosis.- Subacute toxoplasmosis.- Chronic toxoplasmosis.- Relapse.- Comparative clinical aspects.- Epidemiologic studies.- Diagnosis.- Fetal toxoplasmosis as sequel to acute infection of the mother.- Toxoplasmosis transmitted during chronic maternal infection.- Habitual abortions and embryopathies.- Sterility.- Prevention of toxoplasmosis.- Chemotherapy of toxoplasmosis.- Summary.- Mycotic Diseases in Mammalian Reproduction.- Mycosis of the uterus, placenta and fetus.- Fungus infections in cattle.- Fungus infections in horses.- Fungus infections in dogs.- Candidiasis, cryptococcosis and coccidioidomycosis in man.- Pathology of bovine and equine mycotic infection.- Pathogenesis.- Mycosis of the male reproductive system.- Conclusions.- Comparative Aspects of Reproductive Failure Induced in Mammals by Viruses.- Rubella virus infections of man.- Cytomegalovirus infection of man.- Equine virus abortion.- Equine infectious anemia (Swamp fever).- Infectious bovine rhinotracheitis (Rednose).- Bovine viral diarrhea virus.- Hog cholera (Swine fever).- Blue tongue.- Scrapie (Visna).- Summary.- A Model for Virus Induced Reproductive Failure: Theory, Observations and Speculations.- Virus induced cerebellar ataxia.- Summary.- Round Table Discussion on Placental Pathology.- The number of vessels in the umbilical cord.- Gestational pathology and maternal diabetes mellitus.- Experimental viral infection of the placenta.- The lobular architecture of the human and rhesus placenta.- Degeneration of overcrowded placentae.- A uterine-amniotic pathway of infecting the rabbit fetus with Listeria monocytogenes.- Ontogenesis of the Immune Response.- Techniques of intrauterine fetal surgery.- Immunization and skin grafting of the fetus.- Thymectomy of the fetus in utero.- Permanent indwelling catheterization of the fetus in utero.- The timing of immunogenesis in the developing animal.- Antibody formation.- Homograft rejection.- Fetal lymphoid development.- Significance of immunologic immaturity.- The consequences of active immune responses by the fetus.- Beneficial consequences of active fetal immunity.- Antibody formation and hypersensitivity.- Homograft rejection.- Deleterious consequences of active fetal immunity.- Summary.- Immunological Interactions between Mother and Fetus.- Preimplantation immunological phenomena.- Implantation.- Kole of placenta.- Barrier function.- Transplantation antigens.- Trophoblast and its functions.- Fibrin layer of placenta.- Passage of cells.- Deportation of trophoblast.- Antigenicity of fetus.- Maternal immunological reactivity.- Specific immunological interactions between mother and fetus.- Hemolytic disease.- Leucoagglutinins.- Platelet antibodies.- Borrowed immunity.- Graft vs. host reaction.- Protein polymorphism.- Common antigens of placenta.- Choriocarcinoma.- Immunologic unreactivity.- Malformations produced by antibodies.- Conclusions.- Reproduction at High Altitudes.- Oxygen transfer from mother to fetus.- Physiologic condition at sea level.- Safety features.- Adjustments at high altitude.- Possible reproductive failure at high altitude.- In animals.- In man.- Historical aspects.- Congenital defects.- Summary.- Fertility and Reproductive Performance of Grouped Male Mice.- Materials and methods.- Crowding experiment I: Effects on reproductive performance.- Crowding experiment II: Effects on adrenals, reproductive organs and electroejaculation test.- Electroejaculation test.- Statistical analysis of data.- Results.- Crowding experiment I: Effects on reproduction.- Mortality and fertility.- Ovulations per pregnancy.- Implantations per pregnancy.- Litter size and intrauterine mortality.- Loss of ova between ovulation and implantation.- Sex ratio of offspring.- Crowding experiment II: Effects on adrenals, reproductive organs, and electroejaculation test.- Organ weights.- Results of electroejaculation tests.- Relation of testicular weights to semen characteristics.- Discussion and conclusions.- Closing Remarks.- Remarks.