Studies on the physiology of reproduction in the ewe

1. The age at puberty in the females of most domesticated breeds of sheep is 6 to 9 months and ewes are fertile at this age. There is evidence to suggest that certain of the more primitive breeds do not reach puberty until the second autumn after birth.2. In the ewe, sterility does not result from in- :creasing age so long as general bodily health is retained. It is suggested that the gradual decrease in fecundity during later life is due to declining bodily health.3. A brief account is given of the growth and differentiation of the reproductive organs from birth to sexual maturity.4. There is a well defined prepubertal phase of rapid growth in the uterus and ovaries. The uterine glands are formed during this phase.5. The fundamental nature of the mammalian breeding season is emphasised and its evolutionary significance is discussed.6. A survey of published data regarding the breeding season in domesticated sheep has been made.7. The duration of the breeding season in Scottish sheep has been determined by direct observation of a small flock and by the observation of ovarian activity in slaughtered ewes.It was found that, in mature Scottish sheep generally, the breeding season lasts from about the middle of October until about the end of February and includes about 7 or 8 dioestrous cycles. Exceptionally, it may last for as much as 7 months and include 12 or more cycles.8. In ewe lambs 6 to 9 months old the breeding season commences about a month later and ends about a month earlier than in mature animals.9. The existence of breed differences affecting the duration of the breeding season is noted and evidence is produced to show that there are no considerable differences between the various Scottish breeds in this respect.10. Minor differences in nutritive conditions do not affect the duration of the breeding season.11. The average date of onset of the breeding season is subject to breed differences: most of the Scottish breeds do not differ greatly from one another in this respect but the Shetland breed comes into season fully a month later than the others.12. There is evidence to suggest that, in breed crosses, "early breeding" behaves as a dominant or incompletely dominant genetic character.13. Nutritive "flushing" hastens the onset of the breeding season. It is suggested that an improvement in nutritional conditions converts phases of follicular maturation which would not otherwise be accompanied by the manifestation of heat into normal heat periods, and does not hasten follicular maturation (see also 32).14. The effects of climate and environment upon the limits of the breeding season are discussed and the absence of comparative data noted.15. The influence of seasonal changes in the environment upon the onset of the breeding season is discussed in relation to the cause of the restriction of the breeding season, and the tentative hypothesis is advanced that reproductive activity in the ewe is limited primarily by the diurnal duration and intensity of daylight, but that warm climates are conducive to high reproductive activity in the sheep as in other mammals.16. The duration and intensity of light are thought to influence reproductive activity through the anterior pituitary gland. Inhibition of pituitary activity by substances elaborated by photochemical reactions in the eye during anoestrum is suggested as a possible mechanism.17. The results of an experiment designed to test the hypothesis that light is the principal factor in controlling reproductive activity in the ewe are presented and discussed. The results of this experiment were suggestive but inconclusive.18. The conclusion of previous authors that wild sheep are monoestrous is criticised.19. The durations of 63 normal dioestrous cycles and of 77 normal oestrous periods have been determined. The mean duration of the dioestrous cycle was 16.4 days (mean deviation ± 0.8 days) the modal duration was 16.5 days and the range of variation was from 15 to 18.5 days. The mean duration of oestrum was 36 hours (mean deviation ± 22 hours), the modal duration was 28 hours and the range of variation was from 3 to 84 hours.I20. The mean duration of the dioestrous cycle deduced from all available data and representing 697 cycles was 16.8 days, and the chief modal duration was 17 days. The range of variation was from 6 to 68 days but the distribution was multimodal.21. It is suggested that multiplication of the cycle duration takes place as a result of the occurrence of normal ovulation without the exhibition of the mating instinct (see also 32)22. The influences of internal and external factors upon the dioestrous cycle are discussed. It is thought that breed,age, climate, environment and nutrition may all affect the duration and periodicity of oestrum slightly but conclusive evidence is lacking. Sterile service does not affect the cycle in any way.23. Removal of the corpus luteum appears to cut short the dioestrous cycle but the evidence for this is slight.24. Long heat periods are more intense than those which are of short duration.25. There is no correlation between the duration of heat and the duration of the preceding or subsequent dioestrous cycle, but there is a negative correlation between the duration of heat and the duration of both preceding and subsequent interoestrous periods.26. The end of heat is more labile than its commencement.27. It is postulated that the intensity and duration of heat are determined by the amount of heatcausing hormone released during the maturation of the follicle and that heat ceases when the amount of this hormone in the blood falls below a certain threshold value. The time of ovulation is not thought to affect the duration of heat unless it is definitely delayed.28. The changes in the behaviour and in the external genital organs of the ewe during the dioestrous cycle are described.29. It is concluded that it is possible to determine the limits of the heat period only by observing the mutual behaviour of the ram and ewe.30. Heat comes on very rapidly and disappears slowly.31. The gross changes in the ovaries during anoestrum and the dioestrous cycle are described. During anoestrum follicular maturation and rupture are in abeyance. Each dioestrous cycle is associat- :ed with the growth and rupture of a crop of Graafian follicles, with the development from the ruptured follicles of corpora lutea, and the subsequent atrophy of these. 32. Conclusive evidence is presented to show that normal maturation and rupture of Graafian follicles and the development of corpora lutea occur prior to the commencement of the breeding season and occasionally during the breeding season without the exhibition of the mating instinct. 33. Interoestrum is associated with the development of corpora lutea. Full development of the corpora is attained by about the eighth day after the commencement of heat. Atrophy sets in on about the sixteenth day of the cycle and is soon followed by the onset of a new heat period. 34. Oestrum is associated with the very rapid increase in size of one or more Graafian follicles. These rupture about mid -oestrum. 35. Growth curves illustrating the development of the Graafian follicle and the development and atrophy of the corpus luteum during the dioestrous cycle are given. 36. The diameter of the follicle at the time of rupture varies considerably but it is usually about 10 millimetres. 37. The changes in the follicle immediately before rupture are described. 38. The literature on the subject of the cause of ovulation in mammals is discussed, and it is concluded that although the stimulus to follicular maturation and dehiscence probably originates from the pituitary gland, the immed- :iate cause of rupture is the accumulation of fluid, probably chiefly blood plasma, within the follicle. 39. Published data regarding the time of ovulation in the ewe are reviewed and it is concluded that ovulation in those breeds for which data are available takes place about 30 hours after the commencement of heat. 40. Reasons are given for the belief that ovulation occurs about 18 to 24 hours after the commencement of heat in Scottish sheep. 41. Ovulation is entirely spontaneous and there is no evidence that it can be hastened by coitus. 42. The view is adopted that heat is caused by a hormonic stimulus emanating from the ovaries during the time when follicles are maturing, but that the hormone produced by the ovary does not itself stimulate the nervous system but is effective through a further hormonic link. 43. It is thought that the immediate regulator of oestrous periodicity is the corpus luteum and it is postulated that the life of the corpus luteum is determined by the duration of secretion, probably by the pituitary, of some substance necessary for the life of the luteal cells, or perhaps by the rhythmic secretion of some substance inhibiting luteal growth. 44. The anatomy and histology of the uterus, cervix and vagina are described briefly, and a detailed account is given of the modifications in the structure of these organs associated with the dioestrous cycle and with anoestrum. 45. The uterus is slightly congested during oestrum and early metoestrum; slight extravasation of blood sometimes occurs in late oestrum or early metoestrum and there may be haemorrhage into the uterine lumen, but the amount of blood discharged is rarely sufficient to be detectable macroscopically. During anoestrum the uterus becomes anaemic. 46. The uterine stroma becomes oedematous during oestrum and early metoestrum. 47. During anoestrum the epithelium of the uterus and the uterine glands is reduced to cubical or low columnar form and the lumina of the glands are occluded. The amount of cytoplasm in the epithelial cells is greatly reduced and it is non - granular and non -vacuolated. There is no secretory activity. 48. Oestrum is marked by a phase of secretory and degenerative changes in the epithelia of the uterine surface and glands. The limits of this phase are subject to considerable variation. 49. During interoestrum these epithelia hypertrophy and secretory activity is in abeyance. 50. There is a phase of mitotic activity in the uterine epithelia lasting from about the time of ovulation until about the sixth day of the cycle. During dioestrum and early oestrum mitotic activity is in abeyance. 51. The stroma nuclei hypertrophy slightly during dioestrum. Mitotic division of the stroma nuclei is most common during the same phase of the cycle in which mitosis occurs in the epithelia, but is always rare. 52. Lymphocytes are present in the uterine mucosa during all phases of the dioestrous cycle and their number shows no cyclical variation. They are distributed throughout the mucosa and pass through the epithelia into the lumina of the uterus and uterine glands. Leucocytes are found in the uterine mucosa only during pregnancy and the puerperium. 53. The uterine mucosa is usually deeply pigmented, especially on the cotyledons. The pigmentation is due to the presence of a subepithelial layer of melanoblasts. Pigmentation bears no relation to the stages of reproductive activity except that it largely disappears in pregnancy. It is found in prepubertal and in foetal animals. The melanin is identical with that in the skin. The Fallopian tubes are similarly pigmented. 54. There appear to be breed differences in the occurrence of uterine pigment but pigment is found in the uteri of all common Scottish breeds of sheep. 55. It is suggested that the pigment possesses no functional significance. 56. Other pigmented cells which are not dendritic and in which the pigment is non -granular are found during involution of the uterus. The pigment in these cells is probably of haematogenou s origin. 57. The vagina, vestibule and vulva become congested and oedematous during early oestrum. Haemorrhage does not take place. 58. Relaxation of the vaginal muscles occurs in oestrum. 59. There are no secretory cells in the vaginal epithelium. 60. Proliferation of the stratum germinativum of the vaginal epithelium is continuous during the dioestrous cycle but there is a slight increase in the frequency of mitosis during early oestrum. Mitoses are rare during anoestrum. 61. Intensive desquamation of the superficial layers of the vaginal epithelium takes place late in oestrum or early in metoestrum. At this time 4 or 5 layers of cells may be cast off. Slight desquamation takes place continuously throughout the dioestrous cycle and in anoestrum. 62. The thickness of the vaginal epithelium is greatest during oestrum, is reduced by the metoestrous desquamation and increases slowly through dioestrum. In anoestrum the epithelium is reduced below the metoestrous level. 63. Partial keratinisation of the superficial layers of the vaginal epithelium may occureat any time during the dioestrous cycle and in anoestrum but is essentially characteristic of late oestrum and metoestrum. Keratinisation is always regional. 64. Desquamation of the vaginal epithelium is not caused by keratinisation. 65. Lymphocytes are constantly present in the vaginal mucosa. They show no variation in number during the dioestrous cycle but are reduced in number during anoestrum. 66. Invasion of the vaginal mucosa and lumen by polymorphonuclear leucocytes may occur at any phase of the dioestrous cycle and in anoestrum but the tendency towards leucocytosis is greatest during dioestrum and least during anoestrum. Iiechanical stimulation of the vaginal mucosa greatly increases the tendency towards leucocytec. infiltration. 67. Changes in the character of the vaginal mucosa similar to those which occur during the dioestrous cycle take place during the last month of anoestrum in association with the cycles of follicular maturation and rupture which occur at that time, unaccompanied by the exhibition of "heat". 68. The glandulae vestibulares majores are vestigial and are thought to be devoid of functional significance. 69. The muscles of the cervical canal relax during oestrum. 70. The epithelium of the cervical canal is composed entirely of mucus-secretory cells. 71. Secretion of mucus takes place continuously throughout the dioestrous cycle but is most intensive during oestrum. There is no secretion of mucus during, anoestrum but slight amounts may be found in the epithelial cells. 72. The mucus secreted during interoestrum is tenacious and remains in the cervical canal, forming a rudimentary cervical plug. 73. During oestrum the cervical plug liquefies and the mucus flows into the vagina. The mucus secreted at this time is also fluid. 74. The liquefaction of the cervical mucus commences shortly before the onset of heat but the highest concentration of mucus in the vagina does not occur until heat is well advanced. !75. The value of the vaginal smear as a diagnostic measure in determining the stages of reproductive activity is discussed. 76. There are no gross changes in the mammary glands during the dioestrous cycle. 77. A brief description of the changes in the reproductive organs during pregnancy is given and the changes in the uterine mucosa associated with the early development of the foetus and attachment of the foetal membranes are described in detail. 78. The development of the foetus is very slow until about the 15th day and thereafter very rapid until about the 27th day. 79. Attachment of the foetal membranes to the uterine mucosa commences to take place on about the 26th day after coitus: it does not commence until the allantois has become attached to the chorion and the uterus is distended by the expanding allantois. The embryo is in an advanced state of development before attachment begins. 80. Slight atrophy of the corpora lutea occurs on about the 15th day of pregnancy. They recover and become more strongly vascularised by the 18th day. 81. At about the 15th day secretory and degenerative changes commence to occur in the epithelium of the uterus and the epithelium of the uterine glands. Secretory activity continues throughout pregnancy in those parts of the surface epithelium which are in contact with the foetal membranes but where the foetal membranes are not in contact with the mucosa the epithelium hypertrophies without secreting. 82. It is postulated that the presence of the foetus does not affect the normal dioestrous cycle until atrophy of the corpus luteum sets in. The secretory and degenerative changes in the uterine mucosa which then occur are thought to provide the foetus with the materials for rapid growth and the expansion of the foetal membranes is thought, by stimulating the uterine mucosa, to arrest the atrophy of the corpus luteum. 83. The epithelium covering the cotyledons is denuded, by the phagocytic and digestive action of the foetal trophoblast. There is also slight erosion of the stroma and the surface capillaries break down. 84. The attachment of the foetal membranes is a reciprocal process in which both a burrowing action of the foetal trophoblast and hypertrophy of the stroma are involved. 85. The formation of the decidua is largely effected by hypertrophy of the stromal cells and by expansion of the intercellular spaces but there is also proliferation of the stroma. 86. Modification of the cotyledons does not take place unless the mucosa is in contact with the allantochorion. Contact with the trophoblast alone is insufficient to induce change in the stroma. 87. The placental barrier is of the syndesmochorial type. 88. The uterine glands secrete intensively through- :out pregnancy and become greatly dilated. 89. Until the 26th day the foetus is entirely dependant upon the secretions of the uterine epithelium and glands for its nourishment and it is postulated that these secretions constitute the principal source of nourishment of the foetus throughout pregnancy. 90. Atrophy of the corpora lutea of pregnancy commences at about the 18th week and the corpora are markedly atretic at the time of parturition. 91. Follicular maturation is completely in abeyance during pregnancy and the follicles which are present at the time of conception atrophy. Atrophy of the corpora lutea is followed by, follicular growth but maturation and rupture of follicles do not occur until the following autumn. 92. It is concluded that follicular growth is inhibited by a secretion of the corpus luteum. 93. During pregnancy the cervical canal becomes distended by the accumulation within its lumen of mucus secreted by its epithelium. Secretion of mucus continues throughout pregnancy. 94. At parturition the mucus plug liquefies and great, quantities of mucus flow into the vagina. 95. During pregnancy the superficial layers of the vaginal epithelium tend to become converted into cubical or columnar cells resembling in some ways the mucus secretory cells of the cervical epithelium, but mucus is never formed. 96. Desquamation ceases and keratinised cells are never found in the vagina during the later stages, of pregnancy. Leucocytic infiltration is reduced to the anoestrous level. 97. The changes in the uterus, cervix and vagina during the dioestrous cycle are compared with those which occur during pregnancy: the functional significance and the relations of the changes to ovarian secretions are discussed. The changes are compared also, to those which have been described in other mammals. 98. The hypertrophic changes in the epithelia of the uterine mucosa during int ero estrum are regarded as analogous to those which occur during pregnancy, and are throught to be due to the presence of a luteal hormone. They are thus considered to be equivalent in physiological significance to those which occur in the rodents during "pseudo- :pregnancy". 99. The degenerative changes occurring in the uterus during oestrum are considered to be equivalent to both the pro- oestrous and the pseudopregnant degenerative phases in the bitch, the two being superimposed in the ewe by the rapid onset of heat following degeneration of the corpora lutea of the previous cycle. 100. The rudimentary mucus plug formed during inter - :oestrum is regarded as the physiological analogue of the true mucus plug formed during pregnancy. The secretion of mucus is thought to occur under the influence of the ovarian follicular hormone. 101. The liquefaction of the cervical mucus which occurs during oestrum is not regarded as equivalent to that which occurs in parturition. Liquefaction is thought to be a non - specific effect due, probably, to vascular congestion of the cervix. 102. The primary function of the cervical mucus is thought to be the sealing of the cervix during pregnancy. 103. Keratinisation and desquamation of the vaginal epithelium are thought to be remote effects of the ovarian follicular hormone and to be devoid of functional significance. 104. Some possible bearings of this study upon the problem of the factors controlling fertility in the ewe are discussed. It is suggested that increased fertility as a result of nutritive "flushing" may be due to the prevention of death and resorption before attachment of the membranes to the uterine mucosa has taken place, of some of the foeti in multiple pregnancies; and that "flushing" may not influence the number of ova shed during oestrum