The spermatozoa of most invertebrates (e.g., sea urchins) and nonmammalian vertebrates (e.g., fishes and amphibians) have full capacity to fertilize eggs upon leaving the testis. Testicular spermatozoa of mammals, on the other hand, do not possess the ability to do so. Their fertilizing capacity develops as they pass through the epididymis (Young, 1931; Nishikawa and Waide, 1952; Blandau and Rumery, 1964; Bedford, 1966; Orgebin-Crist, 1967). This process, apparently “unique” to mammals, is referred to as the epididymal maturation of spermatozoa. Even after their maturation, however, spermatozoa require an additional phase of maturation or capacitation within the female genital tract before they are able to fertilize eggs (Austin, 1951, 1952; Chang, 1951a). Thus, epididymal maturation and capacitation are two extra steps that mammaliam spermatozoa must take before they can effect fertilization. In this chapter, I will discuss how mammalian spermatozoa prepare themselves for fertilization and how the spermatozoa and eggs interact during fertilization. The process and mechanisms of sperm transport in the female genital tract will not be dealt with extensively here. Readers are referred to Bishop (1961, 1969), Blandau (1969), Bedford (1970b, 1972b), Thibault (1972, 1973a), Zamboni (1972), Blandau and Gaddum-Rosse (1974), Hafez and Thibault (1975), Overstreet and Katz (1977), Overstreet and Cooper (1978, 1979b), Overstreet et al. (1978), Shalgi and Kraicer(1978), Cooper et al. (1979) and Hunter (1975, 1980). The rejection or elimination of extra spermatozoa by the fertilized egg, one of the most fascinating events in fertilization, will not be discussed here. Instead, readers are referred to the chapter by Dr. Wolf in this volume. The physiology of egg activation has been described and discussed to some extent by Gwatkin (1977) and Yanagimachi (1978a). There are numerous reviews dealing with general aspects of mammalian fertilization. The following are recommended to aid in grasping the outline of mammalian fertilization: Austin and Bishop (1957), Austin and Walton (1960), Austin (1961, 1968), Blandau (1961), Piko (1969), Thibault (1969), Bedford (1970a,b, 1972b), Gwatkin (1976, 1977), Yanagimachi (1977, 1978a), Bedford and Cooper (1978) and Hunter (1980).

Mechanisms of Fertilization in Mammals

The abundance of data pertaining to the metabolism of lipids in relation to mammalian fertilization has warranted an effort to assemble a molecular membrane model for the comprehensive visualization of the biochemical events involved in sperm capacitation and the acrosome reaction. Derived both from earlier models as well as from current concepts, our membrane model depicts a lipid bilayer assembly of space-filling molecular models of sterols and phospholipids in dynamic equilibrium with peripheral and integral membrane proteins. A novel feature is the possibility of visualizing individual lipid molecules such as phosphatidylcholine, phosphatidylethanolamine, lysophospholipids, fatty acids, and free or esterified cholesterol. The model illustrates enzymatic reactions which are believed to regulate the permeability and integrity of the plasma membrane overlying the acrosome during interactions between the male gamete and capacitation factors present in fluids of the female genital tract. The use of radioactive lipids as molecular probes for monitoring the metabolism of cholesterol and phosphatidylcholine revealed the presence of (1) steroid sulfatase in hamster cumulus cells, (2) lecithin: cholesterol acyltransferase in human follicular fluid, (3) phospholipase A2, and (4) lysophospholipase in human spermatozoa. These enzymatic reactions can be integrated into a pathway that provides a link between the concepts of lysophospholipid accumulation in the sperm membranes and alteration of the cholesterol/phospholipid ratio as factors involved in the preparation of the membranes for the acrosome reaction. Capacitation is viewed as a reversible phenomenon which, upon completion, results in a decrease in negative surface charge, an efflux of membrane cholesterol, and an influx of calcium between the plasma and outer acrosomal membranes. Triggered by the entry of calcium, the acrosome reaction involves phospholipase A2 activation followed by a transient accumulation of unsaturated fatty acids and lysophospholipids implicated in membrane fusion which occurs during the formation of membrane vesicles in spermatozoa undergoing the acrosome reaction.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mrd.1120120209

A molecular membrane model of sperm capacitation and the acrosome reaction of mammalian spermatozoa

Sex hormones and headache

1 Chemistry and Analysis of Sialic Acid.- I. Historical Background.- II. Natural Occurrence of Sialic Acids.- III. Isolation and Purification.- IV. Chemistry of Sialic Acids.- A. Basic Structures.- B. Stereochemistry.- C. Chemical Reactions and Derivatives.- V. Synthesis.- VI. Quantification of Sialic Acids.- A. Colorimetric and Fluorometric Assays.- B. Enzymatic Assay.- C. Gas-Liquid Chromatography.- VII. References.- 2 The Natural Occurrence of Sialic Acids.- I. Introduction.- II. The Natural Occurrence of Sialic Acids.- A. Viruses.- B. Bacteria.- C. Plants.- D. Invertebrates.- E. Primitive Chordates.- F. Vertebrates.- III. Evolution of Sialic Acids.- IV. References.- 3 The Distribution of Sialic Acids Within the Eukaryotic Cell.- I. Introduction.- II. Extracellular Sialic Acids.- III. Distribution within the Cell.- A. The Plasma Membrane.- B. Endoplasmic Reticulum.- C. Mitochondria.- D. Nuclei.- E. Other Fractions.- IV. Conclusions.- V. References.- 4 Anabolic Reactions Involving Sialic Acids.- I. Introduction: Perspective and Directions.- II. Biosynthesis of the Sialic Acids.- A. Glucose to Sialic Acid.- B. Activation.- C. Regulatory Problems.- D. Other Derivatizations.- III. Biosynthesis of Polymers, Glycoproteins, Mucins, and Glycolipids Containing Sialic Acid.- A. Colominic Acid Synthesis.- B. CMP-Sialic Acid: Lactose (?-Galactosyl) Sialyltransferase.- C. CMP-Sialic Acid: Glycoprotein (?-Galactosyl) Sialyltransferases.- D. CMP-Sialic Acid: Mucin (?-N-Acetylgalactosaminyl) Sialyltransferase.- E. CMP-Sialic Acid: Ganglioside (Glycolipid) Sialyltransferases.- IV. Thoughts on Physiological Function of Sialic Acids.- V. References.- 5 Catabolism of Sialyl Compounds in Nature.- I. Introduction.- II. Pathways of Degradation.- A. Degradation of Gangliosides.- B. Degradation of Glycoproteins.- III. Cellular Mechanism of Degradation.- A. Lysosomes.- B. Uptake and Disposition of Substrates.- IV. Functional Implications.- V. Concluding Remarks.- VI. References.- 6 Disorders of Ganglioside Catabolism.- I. Introduction-The Catabolism of Gangliosides.- II. Tay-Sachs Disease (Type I GM2-Gangliosidosis).- A. Clinical Aspects.- B. Pathology.- C. Chemistry of the Storage Material.- D. Nature of the Metabolic Defect.- E. Enzymology of Type I GM2-Gangliosidosis.- F. Prenatal Diagnosis and Treatment.- III. Type II GM2-Gangliosidosis.- A. Clinical and Pathological Aspects.- B. Chemistry of the Storage Material.- C. Metabolic Defect-Diagnosis and Treatment.- IV. Other Variant Forms.- A. Type III GM2-Gangliosidosis.- B. Hexosaminidase-A-Deficient Adults.- V. Generalized Gangliosidosis (GM1-Gangliosidosis).- A. Clinical Aspects.- B. Pathology.- C. Chemistry of the Stored Material.- D. Metabolic Defect.- VI. Potentially Related Disorders.- A. Hematoside (GM3)-Gangliosidosis.- B. Animal Model Gangliosidoses.- C. In Vitro Model Studies.- VII. References.- 7 The Biological Role of Sialic Acid at the Surface of the Cell.- I. Introduction.- II. Occurrence, Forms, and Amounts of Sialic Acid Residues at the Surface of the Cell.- III. The Masking of Cell-Surface Antigens by Sialic Acid.- IV. Sialic Acid as a Receptor at Cell Surfaces.- A. Receptor for Lectins.- B. Receptor for Viruses.- C. Receptor for Mycoplasma.- D. Receptor for Hormones.- E. Receptor for Antibodies.- F. Receptor for Circulating Glycoproteins.- G. Receptor for Tetanus Toxin.- V. Sialic Acid in Normal and Malignant or Transformed Cells.- VI. Role of Sialic Acid in Cell-to-Cell Interaction.- A. Cellular Adhesion.- B. Intercellular Aggregation.- C. Agglutination.- VII. Physiological Role of Sialic Acid Residues.- A. Transport of Ions, Amino Acids, and Proteins.- B. Phagocytosis.- C. Anaphylactic Shock, Hypercapnia, and Brain Excitability.- D. Lymphocyte Stimulation.- E. Sperm Capacitation.- VIII. Conclusion.- IX. References.- 8 The Altered Metabolism of Sialic-Acid-Containing Compounds in Tumorigenic-Virus-Transformed Cells.- I. Introduction.- II. Experimental Procedures.- A. Cells and Cell Culture.- B. Isolation, Identification, and Quantification of Gangliosides.- C. Assay of Enzymes Involved in Glycolipid Metabolism.- III. Ganglioside Metabolism in Cultured Mouse Cell Lines.- A. Distribution of Gangliosides in Normal and Virally Transformed Cells.- B. Enzymatic Studies.- C. Effect of Growth and Culture Conditions on Ganglioside Metabolism.- D. Sialic-Acid-Containing Glycolipids in Transformed Cells Obtained from Other Species.- VI. Sialic Acid and Glycoproteins in Transformed Cells.- A. Sialic Acid and Sialyltransferase Activity in Transformed Cells.- B. Membrane Glycoproteins.- C. Glycopeptides of Transformed Cells.- D. Role of Sialic Acid and Sialyltransferase.- E. Comments.- V. Relationship between Viral Transformation and Altered Ganglioside Metabolism.- A. Productive Infection of Mouse Cells.- B. Ganglioside Metabolism in Flat Revertant Cell Lines.- C. Specificity of the Altered Ganglioside Metabolism.- D. Generality of the Phenomenon.- E. Transformation of Mouse Cells by RNA Tumor Viruses and Other Agents.- VI. Discussion.- A. Molecular Basis of Altered Ganglioside Metabolism.- B. Significance.- VII. Concluding Remarks.- VIII. References.- 9 Circulating Sialyl Compounds.- I. Introduction.- II. Normal Plasma Constituents.- A. Circulating Sialoenzymes.- B. Serum Sialoglobulins.- C. Sialoglycoprotein Hormones.- III. Circulating Sialoglycoproteins in Abnormal Physiological States.- A. Diabetes.- B. Inflammatory Reactions.- C. Infectious Psychoses.- D. The Effect of Steroid Hormones.- E. Liver Disease.- F. Virus Inhibition of Hemagglutination.- G. Cancer.- H. Diet.- IV. Role of Sialic Acid in Circulating Sialoglycocompounds.- V. References.- 10 Sialidases.- I. Background and Nomenclature.- II. Bacterial Sialidases.- A. Occurrence of Microbial Sialidases.- B. Organismic Characterization and Induction of Bacterial Sialidases.- C. Purification of Bacterial Sialidases.- D. Size and Properties of Bacterial Sialidases.- E. Mode of Action of Bacterial Sialidases.- F. Biological Roles for Bacterial Sialidases.- III. Viral Sialidases.- A. Morphology and Genetics of Viral Sialidases.- B. Purification of Viral Sialidases.- C. Size of Viral Sialidases.- D. Properties of Viral Sialidases.- E. Possible Biological Roles for Viral Sialidases.- IV. Experimental Use of Microbial Sialidases.- V. Mammalian Sialidases.- A. Organ Distribution of Mammalian Sialidases.- B. Subcellular Distribution of Mammalian Sialidases.- C. Purification of Mammalian Sialidases.- D. Assay of Mammalian Sialidases.- E. Physical Properties of Mammalian Sialidases.- F. Developmental Studies of Mammalian Sialidases.- G. Possible Biological Roles of Mammalian Sialidases.- H. Sialidase Activity in Cells in Tissue Culture.- VI. References.

Biological roles of sialic acid

PIP: Migraine headaches appear to be linked to the menstrual cycle and the use of oral contraceptives (OCs). Migraine attacks occur during menses in 60% of women and appear to be related to the withdrawal of estrogen. The fluctuations in estrogen levels associated with migraine headaches produce biochemical changes in prostaglandin production, prolactin release, and opoid regulation. Treatment seeks to interrupt the pathophysiological sequence of menstrual-related migraine through the administration of nonsteroidal anti-inflammatory drugs, ergotamine, or, in refractory cases, hormonal agents. The frequency of migraine decreases with age, but tends either to regress or worsen during menopause. In some cases, estrogen replacement therapy for menopausal symptoms produces headache and it may be necessary to reduce the estrogen dose or change from conjugated estrogen to pure estradiol or estrone. The incidence and severity of migraines are also affected by OC use. OCs may trigger migraine episodes and exacerbate or alleviate pre-existing headache. This variable response seems to be a result of individual differences in intrinsic estrogen neuronal response. Although migraine itself may be a risk factor in stroke, there is no evidence that this risk is increased in migrainers who use OCs.

Estrogens, progestins, and headache.

Cell polarography. II. Effect of neuraminidase and follicular fluid upon the surface characteristics of human spermatozoa.

Incidence of side effects with contraceptive placebo.

The limited clinical usefulness of taking a history in the evaluation of women with tubal factor infertility

Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg).

Background: The efficacy of contraceptives is affected by its route and ease of administration. Herein, both pharmacokinetics and pharmacodynamics of the once-a-month combined injectable contraceptive medroxyprogesterone acetate (MPA) plus estradiol cypionate (E2-Cyp) were compared after intramuscular (IM) or subcutaneous (SC) injection in women of reproductive age. Study Design: Thirty women were randomly assigned to the SC (n=15) or IM (n=15) route of MPA 25 mg+E2-Cyp 5 mg administration. Serum samples were obtained daily for 7 days and then three times a week for 40 days in order to quantify E2, progesterone and MPA. In addition, three ultrasounds were performed on each subject to determine follicular development, and a daily record of the bleeding pattern and side effects was maintained. Results: A comparative analysis showed that the main pharmacokinetic (peak serum concentration, peak serum time, area under the serum concentration vs. time curve, absorption half-life and elimination half-life) and pharmacodynamic parameters, such as follicular development and ovulation, were similar in the SC vs. IM groups. Complete suppression in ovarian function was present in all women. The bleeding patterns and side effects were similar in both groups. Conclusions: The results presented herein demonstrate that the injection of 25 mg of MPA plus 5 mg of E2-Cyp has similar efficacy and safety with either the SC or IM route of administration. The SC option can be considered a viable self-administered contraceptive option that might increase women's compliance to contraceptive use.

Original research article Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg)

Roger Lara-Ricalde

Papers

Cell polarography. II. Effect of neuraminidase and follicular fluid upon the surface characteristics of human spermatozoa.

Incidence of side effects with contraceptive placebo.

The limited clinical usefulness of taking a history in the evaluation of women with tubal factor infertility

Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg).

Original research article Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg)